RxPG News : Prostate Cancer

Intermittent Androgen Suppression Therapy in the Treatment of Prostate Cancer

Tue, 05 Jan 2010 13:56:42 PST

( from http://www.rxpgnews.com ) 'Potential Benefits of Intermittent Androgen Suppression Therapy in the Treatment of Prostate Cancer: A Systematic Review of the Literature' is the title of an article by P-A. Abrahamsson in the January issue of European Urology, the official journal of the European Association of Urology. The author evaluates available evidence regarding the efficacy and tolerability of intermittent androgen deprivation (IAD) and assess its value in the treatment of prostate cancer (PCa).

Prostate cancer (PCa) is the second most common male cancer worldwide and the most frequently occurring in Europe (20.3% of the total in 2006). Androgen-deprivation therapy (ADT) has progressed since 1941 when surgical castration was shown to improve PCa outcomes. The well-known side effect profile of ADT has significant quality-of-life implications such as sexual dysfunction, hot flushes, fatigue etc. Furthermore, it appears that androgen suppression causes a change in stem cells from an androgen-dependent to an androgen-independent phenotype. Because this progression to androgen independence is thought to begin early after treatment initiation, stopping androgen deprivation prior to this change occurring should restore apoptotic potential and help tumour cells remain sensitive to re-initiating treatment.

The strategy behind IAD, therefore, is to alternate androgen blockade with treatment cessation, allowing hormonal recovery between treatment periods, thus potentially improving tolerability and quality of life.

The author wishes to evaluate available evidence regarding the efficacy and tolerability of IAD and assess its value in the treatment of PCa. Key phase 2/3 clinical trials of IAD in PCa published within the last 10 years were identified on Medline using different search terms.

The conclusions were that IAD seems to be as effective as continuous androgen deprivation while showing tolerability and quality of life advantages, especially recovery of sexual potency. IAD has been a treatment option for >20 years and the EAU considers that its status should no longer be regarded as investigational.

However, QoL data are surprisingly limited given that this, rather than survival, is the key driver for IAD and considering the length of time this approach has been under evaluation.

Based on available evidence and general clinical opinion, IAD is a valid treatment option in nonmetastatic PCa cases, i.e. patients with locally advanced disease with or without lymph node involvement and those experiencing relapse following curative treatment. These patients have a higher chance of survival than those with more advanced disease, making QoL a key consideration. Full results from phase 3 trials, which include both locally advanced and metastatic patients, will further clarify target populations.

IAD has come of age, and many clinicians believe it has earned its place in the management of PCa; however, there are still insufficient data to determine whether IAD has the potential to prevent or reverse the long-term complications associated with ADT.

Inhibition of TNF-receptor associated protein-1possible treatment for prostatic cancer

Wed, 30 Dec 2009 13:28:05 PST

( from http://www.rxpgnews.com ) Current research suggests that TNF-receptor associated protein-1 (TRAP-1) may prevent cancer cell death. The related report by Leav et al, "Cytoprotective Mitochondrial Chaperone TRAP-1 as a Novel Molecular Target in Localized and Metastatic Prostate Cancer," appears in the January 2010 issue of the American Journal of Pathology.

Prostate cancer is the most common type of cancer and is the second leading cause of cancer deaths among men in the United States, following lung cancer. Prostate cancer most commonly develops in men over the age of 50 and is slow-growing; however, it may metastasize to other organs, particular to the bones and lymph nodes. Metastatic phase prostate cancer claims over 30,000 deaths per year in the United States alone.

Prostate cancer cells are often resistant to cell death. Researchers led by Dr. Dario C. Altieri of the University of Massachusetts Medical School, therefore, explored the role of TRAP-1, a protein thought to regulate cell death, in prostate cancer survival. TRAP-1 was highly expressed in both high-grade human prostate cancer lesions and mouse models of prostate cancer, but not in benign or normal prostate tissue. In addition, TRAP-1 overexpression in non-cancer prostate cells inhibited cell death, whereas TRAP-1-deficient prostate cancer cells had enhanced levels of cell death. Moreover, treatment with Gamitrinib, which inhibits TRAP-1, resulted in prostate cancer cell death, but not death of non-cancerous prostate cells. Therefore, targeting TRAP-1 via Gamitrinib treatment may be a viable therapeutic strategy for patients with advanced prostate cancer.

Leav et al suggest that "TRAP-1 [is] a novel marker of localized and metastatic prostate cancer, but not normal glands, required for prostate cancer cell viability, in vivo. Taken together with the preliminary safety of Gamitrinibs in preclinical studies, these data suggest that targeting mitochondrial TRAP-1 may provide a novel therapeutic approach for patients with advanced and metastatic prostate cancer" A similar approach may be also suitable for other types of cancer, as TRAP-1 is broadly expressed in disparate human malignancies. In future studies, Dr. Altieri and colleagues plan to "further dissect the biology of TRAP-1 cytoprotection in cancer cells, and test whether disabling its function may overcome drug resistance, the most common reason of treatment failure and dismal outcome in patients with advanced prostate cancer."

Oncologists present test to predict survival in castration-resistant prostate cancer patients

Sun, 01 Mar 2009 09:12:50 PST

( from http://www.rxpgnews.com ) Dana-Farber Cancer Institute (DFCI) and Source MDx today
announced that Source MDx’s whole blood RNA transcript-based Precision Profiles™ diagnostic test predicted survival in men with castration-resistant prostate cancer (CRPC). In a study of 62 CRPC patients, the model separated patients into a high risk group (survival less than 2.2 years) and a low risk group (survival greater than 2.2 years) (log rank p=0.00083).
The six-gene CRPC Precision Profile™ was 96 percent accurate in predicting low risk CRPC patients alive at study end and 93 percent accurate in predicting high risk CRPC patients who died prior to study completion, suggesting that the model may be a powerful tool for stratifying CRPC patients in clinical trials. The Prostate Cancer Clinical Trials Consortium (PCCTC) will begin a prospective, multisite clinical trial to validate using Source MDx’s six-gene CRPC Precision Profile™ to stratify aggressive vs. non-aggressive CRPC patients.
In the study, circulating tumor cell (CTC) counts were not predictive of survival. In fact, the highest CTC counts (931 and 263) were found in patients from the low risk group. The Halabi nomogram, a commonly used clinical prognostic factor that uses seven clinical measures, also predicted low and high risk groups of men with CRPC, based on evaluations in 56 patients, but was less discriminatory (p=0.012) than the six-gene Precision Profile™.
William K. Oh, M.D., clinical director, Lank Center for Genitourinary Oncology, DFCI today presented the data from abstract 176 in a general poster session at the American Society for Clinical Oncology’s Genitourinary Cancers Symposium. The study was co-investigated with Robert W. Ross, M.D., attending physician, Lank Center for Genitourinary Oncology, DFCI. The PCCTC, a national clinical research group comprised of top U.S. research institutions, including DFCI, will conduct a prospective multi-site validation clinical trial of CRPC patients under the leadership of Dr. Oh. Consortium studies focus on the evaluation of novel agents for the management of prostate cancer at all stages of the disease. Source MDx has filed provisional patents on the six-gene model, which also states diagnostic claims for protein markers corresponding to patented RNA transcripts.
“Survival for castration-resistant prostate cancer ranges greatly from several months to several years, however, there are no available tools that allow clinicians to easily identify patients with the most aggressive form of the disease,” commented Dr. Oh. “The ability to identify patients with more aggressive forms of castration-resistant prostate cancer using a simple blood assay may prove to be a powerful tool for stratifying patients in clinical trials, leading to more robust studies with more relevant survival endpoints. I look forward to further evaluating this biologically-based test in forthcoming larger, multi-site clinical trials with the Prostate Cancer Clinical Trials Consortium.”
These data also show that individual differences in gene transcripts associated with cell-mediated and humoral immunity are associated with survival in CRPC patients. These specific immune system changeswere indicative of a decrease in both cell-mediated and humoral immunity in CRPC patients with higher mortality.
“The six genes predictive of more lethal castration-resistant prostate cancer in this trial suggest a fundamental difference in a patient’s immune system’s ability to deal with malignant tumors when confronted with more aggressive forms of prostate cancer,” stated Karl Wassmann, Chief Executive Officer of Source MDx. “The Source MDx six-gene CRPC Precision Profile™ is now available for patient stratification in prostate cancer clinical trials.”

About the Study:
From August 2006 through June 2008, Source MDx and Dana-Farber Cancer Institute conducted a study to discover whole blood-based RNA-transcript biomarkers predictive of primary end-points of CRPC progression (i.e., survival). The study enrolled a total of 62 CRPC patients, with or without bone metastases, who had previously undergone a variety of treatments, including hormone therapy, chemotherapy and radiation. Each patient consented to the collection of whole blood in PAXgene™ blood RNA tubes for gene expression and CellSave™ tubes for the enumeration of circulating tumor cells (CTCs). Using Source MDx Precision Profiles™, a total of 168 inflammation and prostate cancer-related genes were evaluated using optimized Q-PCR technology to assess biomarkers predictive of survival. Hazard ratio survival analysis models were performed on a weekly basis, both from the time of CRPC diagnosis through June 20, 2008 and from the time of blood draw through June 20, 2008. The results were similar regardless of the survival time definition (the time of castration-resistant diagnosis vs. blood draw) or the survival model used for statistical analysis. Treatment type was not predictive of survival.

PSA levels appear to be predictive of three year prostate cancer risk in African-American men

Wed, 25 Feb 2009 00:43:00 PST

( from http://www.rxpgnews.com ) PSA levels appear to be more predictive of three year prostate cancer risk in African-American men compared with Caucasian men with a family history of prostate cancer, according to a paper published in Cancer Prevention Research, a journal of the American Association for Cancer Research.

"It was previously thought that PSA levels were just naturally higher in African-American men, suggesting a need to possibly adjust the threshold upward before recommending a biopsy," said Veda Giri, M.D., director of the Prostate Cancer Risk Assessment Program at Fox Chase Cancer Center.

Giri and colleagues at the University of Chicago observed 646 high-risk men, of whom 63 percent were African-American, in the Prostate Cancer Risk Assessment Program, which has an aggressive early detection approach.

No "race specific" differences in PSA levels were found when race was measured using genetic markers of ancestry or reported by participants.

The researchers subsequently analyzed men with a PSA between 1.5 to 4 ng/mL, and who had at least one follow-up visit. They found that among men with a family history of prostate cancer, PSA levels had the same predictive value whether the men were Caucasian or African-American.

These findings are unique in that typically men are not recommended for a prostate biopsy until their PSA levels rise above 4 ng/mL. Larger studies with longer follow-up are needed to confirm these findings.

"African-American men and men with a family history of prostate cancer should be encouraged to participate in early detection studies to define personalized screening strategies that may diagnose prostate cancer at a curable point," said Giri.

Survey on PSA screening in young men

Mon, 11 Aug 2008 08:47:50 PST

( from http://www.rxpgnews.com ) A new analysis finds that one in five men in their 40s has had a prostate specific antigen (PSA) test within the previous year and that young black men are more likely than young white men to have undergone the test. The study, published in the September 15, 2008 issue of CANCER, a peer-reviewed journal of the American Cancer Society, provides valuable information as experts discuss possible changes to prostate cancer screening recommendations.

Currently, major medical organizations say evidence is insufficient to recommend routine prostate cancer screening using PSA or digital rectal exam (DRE). Rather, most group recommended men at average risk discuss with their doctor starting at age 50 whether to get tested. The American Cancer Society does though recommend that African Americans and men with a first degree relative with prostate cancer should , have screening every year, begin at age 45, and that men with two or more first degree relatives with prostate cancer begin testing at age 40.

To shed light on current PSA screening practices in young men, Dr. Judd Moul and Dr. Charles Scales, of Duke Prostate Center and Urologic Surgery at Duke University and colleagues obtained data from the 2002 Behavioral Risk Factor Surveillance System, an annual, population-based survey of civilian, non-institutionalized adults in the United States. The final sample for this study consisted of 58,511 men ages 40 and above.

The investigators found that one in five of them men had undergone screening in the previous year. Several sociodemographic characteristics were associated with PSA screening in younger men. In particular, young, black, non-Hispanic men were more likely than young white, non-Hispanic men to report having a PSA test in the previous year. This finding was independent of income, education and access to care. The authors noted that these results are reassuring, showing that physicians are more likely to recommend screening among black men due to this group's elevated risk for prostate cancer. However, they also noted that PSA screening in this group remains potentially suboptimal; only about one in three African American men reported having a PSA test in the previous year.

The survey also revealed that younger Hispanic men were more likely to undergo PSA testing than younger white, non-Hispanic men. The probability of undergoing a PSA test was also higher with increasing obesity, as well as with higher household income and education level. Health insurance coverage and an ongoing relationship with a physician were also strongly associated with having had a recent PSA test.

"Our study is the first to specifically examine PSA screening in younger men, which provides an important assessment of quality of care, especially for high-risk groups," the authors write. "Further investigation will be required to understand the impact of new risk-stratification strategies, with particular focus on the policy implications of potentially large increases in health care resource use".

New, noninvasive prostate cancer test beats PSA in detecting prostate cancer

Tue, 05 Feb 2008 22:24:37 PST

( from http://www.rxpgnews.com ) An experimental biomarker test developed by researchers at the University of Michigan more accurately detects prostate cancer than any other screening method currently in use, according to a study published in the February 1 issue of Cancer Research, a journal of the American Association for Cancer Research.

The researchers say a simple urine test that screens for the presence of four different RNA molecules accurately identified 80 percent of patients in a study who were later found to have prostate cancer, and was 61 percent effective in ruling out disease in other study participants.

This is far more accurate than the PSA blood test currently in use worldwide, which can accurately detect prostate cancer in men with the disease but which also identifies many men with enlarged prostate glands who do not develop cancer, researchers say. Even the newer PCA3 test, which screens for a molecule specific to prostate cancer and which is now in use both in the U.S. and Europe is less precise, they say.

Statin use linked with decreased prostate cancer mortality rates; lower PSA levels

Tue, 22 May 2007 09:59:37 PST

( from http://www.rxpgnews.com ) ANAHEIM, Ca. (May 20, 2007) -- Urologists and researchers have postulated in recent years that statin medications could have an impact on the growth and progression of prostate cancer. Cholesterol is a primary building block for testosterone, which has in turn been linked with prostate tumor growth (less testosterone results in slower-growing tumors). In recent years, research has indicated a possible link between dietary fat intake and prostate cancer. Research presented today at the 102nd Annual Scientific Meeting of the American Urological Association explores the effect statin medications (which work to reduce low-density lipoprotein, or LDL, levels) may have on prostate-specific antigen, the incidence of prostate cancer, and mortality due to prostate cancer. A special session for members of the media was held on May 20 at 11:00 a.m. and moderated by AUA spokesman Anthony Y. Smith, M.D. of the University of New Mexico, Albuquerque.

New research supports early testing for prostate cancer

Sun, 20 May 2007 10:04:37 PST

( from http://www.rxpgnews.com ) Prostate cancer is the third-leading cause of cancer deaths among American men and is most treatable when caught in its earliest stages. Research presented today during the 102nd Annual Scientific Meeting of the American Urological Association in Anaheim, Ca. provided further evidence supporting regular prostate-cancer screening and offered new insights into disease progression and the hormonal treatment of recurrent disease. A special session for media highlighting this research was held on May 20 at 9:00 a.m. PDT and was moderated by AUA spokesman Christopher L. Amling, M.D.

Genetic marker linked to aggressive prostate cancer

Sun, 20 May 2007 03:59:37 PST

( from http://www.rxpgnews.com ) Northwestern University researchers have discovered that a recently identified genetic marker for prostate cancer is linked to a highly aggressive form of the disease.

These findings ultimately will aid the development of a simple blood test to predict who is susceptible to this aggressive cancer, Northwestern researchers said. Knowing which patients carry this genetic marker also will guide doctors in how they treat the cancer.

The Northwestern study showed a strong hereditary component to this aggressive cancer. Prostate cancer patients who carry the genetic marker called 8q24 -- are much more likely to have a close family member with the disease. They have a 40 percent chance of having a close family member with prostate cancer. In contrast, prostate cancer patients who do not carry the marker have a 20 percent chance.

The genetic marker is twice as common in African-American men. At least 30 percent of African-American men with prostate cancer carry the genetic marker compared to 15 percent of men of European descent, according to a previous study involving Northwestern.

Prostate cancer is the most common cancer among American men, causing more than 40,000 deaths annually. African-American men have a higher incidence of the disease and get it at a younger age than white men.

These findings will help us understand the mechanisms underlying prostate cancer, said Brian Helfand, M.D., an assistant research professor of urology at Northwestern's Feinberg School of Medicine, a co-principal investigator of the study and a physician at Northwestern Memorial Hospital. They hold great promise for the development of new treatments and prevention.

Helfand is presenting his findings Sunday, May 20, at the American Urological Association meeting in Anaheim, California.

The study looked at more than 550 prostate cancer patients who had been treated at the Robert H. Lurie Comprehensive Cancer Center at Northwestern University. Researchers wanted to identify the characteristics of prostate cancer in men who were carriers of these genetic markers to see if their cancer differed from that in men who did not carry the gene variant.

We found the carriers of these 8q24 markers had more aggressive tumors, said Helfand. Patients who were carriers had cancers that were more likely to spread into the lymph nodes and were more difficult to surgically remove.

The patients in the Northwestern study had been treated by William Catalona, M.D., professor of urology and director of the Clinical Prostate Cancer Program at the Robert H. Lurie Comprehensive Cancer Center. Catalona is a co-principal investigator of the study.

We have the largest and best-detailed prostate cancer population to perform this study because Dr. Catalona has a rich database and follow-up on all of his patients, noted Helfand.

The 8q24 genetic variation was originally discovered by deCODE genetics, a biopharmaceutical company in Iceland, in collaboration with Catalona of Northwestern and two other research groups. That study was first reported in Nature Genetics in June, 2006.

Since then, the genetic variant has been widely duplicated by prestigious genetic research groups around the country. This is the first time that a genetic mutation associated with prostate cancer has been found in a large segment of the population.

The initial study by deCODE genetics showed that men who carry the genetic marker have a 60 percent increase in risk of the disease.

Genetic markers, also called alleles, occupy a specific position on a chromosome. The alleles linked to the aggressive prostate cancer found by Northwestern and other labs over the past year are located on the long arm of chromosome 8.

Study identifies multiple genetic risk factors for prostate cancer

Sun, 01 Apr 2007 11:48:45 PST

( from http://www.rxpgnews.com ) A study led by researchers at the Keck School of Medicine of the University of Southern California (USC) and Harvard Medical School has identified seven genetic risk factorsâDNA sequences carried by some people but not othersâthat predict risk for prostate cancer. According to the study's findings, these risk factors are clustered in a single region of the human genome on chromosome 8 and powerfully predict a man's probability of developing prostate cancer. The paper will be published in the online edition of Nature Genetics on April 1.

"The study has identified combinations of genetic variants that predict more than a fivefold range of risk for prostate cancer," says senior author David Reich, assistant professor of genetics at Harvard Medical School and associate member of the Broad Institute of Harvard and MIT. "Both high- and low-risk combinations of variants are common in human populations."

"The identification of these genetic variants is an important step in helping us understand the higher risk for prostate cancer in African Americans compared with other U.S. populations and, more importantly, why some men develop prostate cancer and others do not," says lead author Christopher Haiman, assistant professor of preventive medicine at the Keck School of Medicine of USC.

While the HMS/USC team identified seven genetic variants on chromosome 8, two other studies published in the same issue of Nature Genetics highlight the importance of this region in prostate cancer and each provides independent support for the findings presented by the HMS/USC team. One of the studies is from deCODE Genetics in Iceland while the other is led by Dr. Gilles Thomas and Dr. Stephen Chanock at the National Cancer Institute. Together, the three studies provide robust evidence of the role genetic variants play in prostate cancer.

According to the HMS/USC study, the seven genetic variants each independently predict risk for prostate cancer, with the predictive strength varying depending on the variant. Because almost all the risk factors were of highest frequency in African Americans, they may contribute to the known higher rate of prostate cancer among African Americans compared with other U.S. populations. The predictive power of the variants may also be useful in the prevention of prostate cancer. "Clinical testing of these genetic variants may help us identify men who should be prioritized for early prostate cancer screening and prevention efforts," says Reich.

The study also produced novel biological findings. It revealed that each genetic contributor to prostate cancer risk is located outside of the coding regions of genes, in regions previously designated as junk DNA. "The discovery of multiple, independent genetic changes that are in close proximity to one another, but outside of any known gene, suggests that these results may also teach us about novel molecular mechanisms whereby DNA changes can alter risk of disease," says Brian Henderson, the paper's senior co-author and dean of the Keck School of Medicine of USC.

Two papers in 2006 highlighted this same chromosomal region as important in prostate cancer. The company deCODE genetics in Iceland first identified two specific genetic variants that contributed to risk for prostate cancer. The HMS/USC group then published a paper that identified a small region (about 4 million nucleotides, or 1/1,000th of the genome) as likely to contain important genetic risk factors. As part of this study, the HMS/USC group carried out a whole-genome screen for prostate cancer genes in about 2,500 African Americans. The paper suggested that more variants were likely in the region.

To find the additional risk factors in the current study, the team systematically tested genetic changes in this region of the genome in roughly 7,500 African American, Japanese American, Native Hawaiian, Latino, and European American men with and without prostate cancer. The majority of the men studied were drawn from the Multiethnic Cohort Study (MEC), an epidemiological study of more than 215,000 people from Los Angeles and Hawaii created in 1993 by USC's Henderson and Laurence Kolonel of the University of Hawaii. The genetic study of the MEC grows out of a multiyear, ongoing collaboration between USC, the University of Hawaii, and collaborators at HMS and the Broad Institute of Harvard and MIT.

Soy-rich Japanese diet decreases the risk of localized prostate cancer, increases the risk of advanced prostate cancer- Study reports

Tue, 27 Mar 2007 00:49:17 PST

( from http://www.rxpgnews.com ) The largest study examining the relationship between the traditional soy-rich Japanese diet and development of prostate cancer in Japanese men has come to a seemingly contradictory conclusion: intake of isoflavone chemicals, derived largely from soy foods, decreased the risk of localized prostate cancer but increased the risk of advanced prostate cancer.

The prospective study of 43,509 men, published in the March issue of Cancer Epidemiology, Biomarkers & Prevention, suggests that the effects of isoflavones on prostate cancer development may differ according to disease stage, say researchers at the National Cancer Center in Japan.

One possible explanation is that isoflavones may delay the progression of latent prostate cancer only; once tumors lose estrogen-receptor beta expression and become aggressive, isoflavones may fail to protect against the development of advanced cancer, and might even increase the risk of progression, possibly by reducing serum testosterone, researchers say. It is also possible that advanced and localized prostate cancer may be different tumor subtypes, which may react differently to isoflavones.

"The present findings provide no clear understanding of when or how localized cancer will develop to aggressive cancer, and of the related effect of isoflavones," said the study's first author, Norie Kurahashi, M.D., of the Epidemiology and Prevention Division of the National Cancer Center.

"Given that Japanese consume isoflavones regularly throughout life, we do not know the period during which the effects of isoflavones on prostate cancer are preventive, and further research is required to find that out, including well-designed clinical trials," she said.

Until those studies are done, the researchers recommend that Japanese men continue to consume isoflavones through their food and not through supplements.

"Consumption of isoflavones from traditional Japanese food throughout life may protect against the incidence of prostate cancer, but we cannot recommend the use of isoflavones from supplements for people who do not regularly consume these chemicals, because the relationship between isoflavones and the risk of advanced prostate cancer is not yet clear," Kurahashi said.

Isoflavones act as both strong antioxidants and plant-based estrogens. Soybeans are the most common source of isoflavones, especially genistein and daidzein, which have been shown in some animal studies to exert a protective effect against prostate cancer.

Japanese men eat significantly more soy-based foods than do Western men, and the incidence of prostate cancer is much lower in Asian countries than in Western countries. Still, reviews of latent, or clinically insignificant, prostate cancer findings in autopsy reports have revealed no difference between the populations so scientists have theorized that isoflavones stop latent cancers from developing further.

But because smaller epidemiological studies in Japan have reached differing conclusions about the protective effects of soy on prostate cancer development, this research team conducted the most comprehensive analysis to date. They polled thousands of men age 40-69 about their consumption of 147 foods, the most popular of which were miso soup (primarily made from fermented soybeans), natto (also a product of fermented soybeans) and tofu, made from soy milk. Japanese consume miso soup more frequently, usually daily, than other soy foods, and miso, natto, and tofu account for about 90 percent of the population's consumption of daidzein and genistein, according to Kurahashi.

The researchers then followed participants from 1995 through 2004 and found that 307 men were diagnosed with prostate cancer. In this group, 74 cases were advanced, 218 were confined to the prostate organ, and 15 were of undetermined stage.

They concluded that intake of genistein, daidzein, miso soup and soy food had no overall link to diagnosis of prostate cancer. However, they calculated that the risk of developing localized prostate cancer was 50 percent lower in men who ate the most isoflavones compared to men who ate the least â meaning that men in the top category ate between two and three times as much isoflavone-rich food.

However, in a discovery they cannot explain, they also calculated that the risk of developing advanced prostate cancer was twice as high in men who consumed two or more bowls of miso soup a day than in men who ate less than one bowl of soup.

They also found that the protective effect of isoflavone-rich food was strongest in men who were older than 60: the more isoflavones they ate, the more they reduced their risk of developing localized prostate cancer. "Isoflavone may be protective for localized prostate cancer only in men aged more than 60 years, and may not have a protective effect in the early stage of prostate cancer in younger men," the researchers conclude in their study.

The inconsistencies in the finding â that isoflavones decreased the risk of localized prostate cancer, but not the risk of advanced prostate cancer â could be errors in food measurement, or could be due to the fact that the number of participants who developed advanced prostate cancer was small, said Kurahashi. Or, as researchers speculate, isoflavones could interact with the estrogen receptor on prostate tissue enough to inhibit production of testosterone, which can fuel prostate cancer. When tumors lose all of their estrogen receptors and stop responding to isoflavone-induced hormonal interference, they grow aggressively.

"A broad body of research is required to clarify the timing and period of isoflavones' preventive effect on prostate cancer development," Kurahashi said.

Green tea and COX-2 inhibitors combine to slow growth of prostate cancer

Thu, 01 Mar 2007 05:34:24 PST

( from http://www.rxpgnews.com ) Drinking a nice warm cup of green tea has long been touted for its healthful benefits, both real and anecdotal. But now researchers have found that a component of green tea, combined with low doses of a COX-2 inhibitor, could slow the spread of human prostate cancer.

In the March 1 issue of Clinical Cancer Research, researchers from University of Wisconsin-Madison demonstrate that low doses of the COX-2 inhibitor celecoxib, administered with a green tea polyphenol called pigallocatechin-3-gallate (EGCG), can slow the growth of human prostate cancer. Their experiments were performed in cell cultures and in a mouse model for the disease.

Celecoxib and green tea have a synergistic effect -- each triggering cellular pathways that, combined, are more powerful than either agent alone, said Hasan Mukhtar, Ph.D., professor of dermatology at the University of Wisconsin and member of Wisconsins Paul Carbone Comprehensive Cancer Center. We hope that a clinical trial could lead to a preventative treatment as simple as tea time.

Previous research has linked the cyclooxygenase-2 enzyme, commonly known as COX-2, to many cancer types, including prostate cancer, said Mukhtar. Mukhtar and his colleagues have previously shown COX-2 inhibitors like celecoxib (known under the brand name Celebrex) suppress prostate cancer in animal models. COX-2 inhibitors also have been shown to cause adverse cardiovascular effects when administered at high doses over long durations.

In 2004, Mukhtar and his colleagues demonstrated that green tea polyphenol EGCG has cancer-fighting abilities of its own. Their study, published in Cancer Research, showed that EGCG can modulate the insulin-like growth factor-1 (IGF-1)-driven molecular pathway in a mouse model for human prostate cancer, pushing the cells toward programmed cell death (apoptosis).

We believed that COX-2 inhibitors may still prove beneficial if used in combination with complementary agents, Mukhtar said. Our studies showed that the additive effect of green tea enables us to utilize the cancer-fighting abilities of COX-2 inhibitors, but at lower, safer doses.

In this latest research, Mukhtar and his colleagues looked at the effects of the two substances on cultured human prostate cancer cells. Alone, both EGCG and NS-398, a COX-2 inhibitor similar to celecoxib, demonstrated the ability to slow cancer cell growth and limit the presence of known cancer-promoting proteins within the cell samples. Together, EGCG and NS-398 suppressed cell growth by an additional 15 to 28 percent.

The researchers repeated the experiment in mouse models of prostate cancer, using celecoxib and an oral suspension of the decaffeinated green tea polyphenol. By using pharmacy-grade celecoxib and actual tea, they had hoped to replicate real-life conditions. The idea is that it would be easier to get people to drink green tea than it would be to take an additional dietary supplement, Mukhtar said.

In mice that were not treated with either substance, the tumor volume averaged 1,300 cubic millimeters, whereas mice given either the tea or celecoxib had tumors averaging 835 cubic millimeters and 650 cubic millimeters, respectively. Tumors taken from mice given both agents, however, measured on average a volume of 350 cubic millimeters.

In parallel to tumor growth inhibition, mice that received a combination of green tea and celecoxib registered a greater decrease in prostate specific antigen (PSA) levels compared to that in celecoxib alone or green tea alone treated animals. PSA is a protein produced by the cells of the prostate and is used as a marker for detection and progression of prostate cancer. These results, combined with a marked decrease in the presence of cancer-promoting proteins, offered clear indications that green tea and celecoxib, combined, could be useful in slowing prostate cancer growth, Mukhtar said.

Prostate cancer typically arises from more than one defect in the cellular mechanics, which means that a single therapeutic might not work fighting a particular cancer long-term, Mukhtar said. If tests in human trials replicate these results, we could see a powerful combined therapy that is both simple to administer and relatively cost effective.

Prostate brachytherapy causes fewer side effects than surgery

Wed, 28 Feb 2007 10:12:57 PST

( from http://www.rxpgnews.com ) Men with prostate cancer have a slightly better long-term side effects profile with radiation seed implants than they do with surgery, according to a study released today in the International Journal for Radiation Oncology*Biology*Physics, the official journal of ASTRO.

Doctors in France conducted the first-ever multi-institutional, comparative study of men with early stage
prostate cancer to evaluate a mans quality of life, treatment-related side effects and cost of the treatment based
on the type of treatment the patient received: surgery or seed implants, both widely-accepted modes of treatment for early-stage prostate cancer. With prostate surgery, called a radical prostatectomy, a surgeon removes the prostate. During prostate brachytherapy, a radiation oncologist places radioactive seeds, similar to the size of a grain of rice, into the prostate to kill the cancer.

In this study, 435 men with prostate cancer were surveyed before treatment, immediately after treatment and subsequently at follow-up exams to gauge their quality of life and treatment-related side effects against predefined materials given to them by the doctors. Doctors found that brachytherapy is a more expensive procedure at the outset, but that follow-up costs related to surgery cause both treatments to cost about the same.

With regard to side effects, surgery had more significant side effects immediately following treatment, but those side effects improved steadily over two years. Brachytherapy, however, showed moderate, but persistent side effects over the two years. Urinary incontinence was more common after surgery; however, urinary irritation was a more common complaint from those who received brachytherapy. Impairment of sexual function was found to be consistently higher among those who received surgery than those who received brachytherapy.

This study is exciting because its the first time we have a comparative study to assess the costs in a given country and see if the side effects are different for patients who received surgery or brachytherapy, said Jean-Marc Cosset, M.D., one of the authors of the study and a radiation oncologist in the Department of Radiation Oncology at the Institut Curie in Paris, France. By looking at these factors, we are better able to tailor a suitable treatment option for the individual patient.

Researcher identifies men who require second prostate biopsy

Thu, 22 Feb 2007 10:06:55 PST

( from http://www.rxpgnews.com ) A researcher in the Oregon Health & Science University Cancer Institute and Portland Veterans Affairs Medical Center has found a way to identify which men need a second prostate biopsy because they may be harboring life-threatening prostate cancer even though they were given a clean bill of health after their first biopsy. Mark Garzotto, M.D., has been invited to present his findings on Thursday, Feb. 22, at the Multidisciplinary Prostate Cancer Symposium in Orlando, Fla. He is the director of urologic oncology at the Portland Veterans Affairs Medical Center, assistant professor of surgery (urology) in the OHSU School of Medicine, and member of the OHSU Cancer Institute. Also involved in the research is Shane Rogosin, M.D., resident, in general internal medicine, and geriatrics, OHSU School of Medicine.

"Until now we've really had no clear and consistent method to recommend further follow up or diagnostic procedures for men who have a negative biopsy. We have derived a simple marker so urologists can identify who is at risk for high-grade prostate cancer," Garzotto said.

Garzotto studied what is considered a large group, 511 men at the Portland Veterans Affairs Medical Center from 1992 to 2006. All had been referred to urology clinics for suspicion of prostate cancer. All patients had one prior negative prostate biopsy. In all, the study included 1,319 biopsies.

What Garzotto found to be the indicator for a repeat biopsy was a high prostate specific antigen (PSA) adjusted for prostate size. A Gleason score of 7 or above was indicative that life-threatening prostate cancer may be present and a repeat biopsy is advised.

A Gleason score is a system of grading prostate cancer tissue based on how it looks under a microscope. Gleason scores range from 2 to 10 and indicate how likely it is that a tumor will spread. A low Gleason score means the cancer tissue is similar to normal prostate tissue and the cancer is less likely to spread; a high Gleason score means the cancer tissue is very different from normal tissue and the tumor is more likely to spread. A high grade of cancer results in a higher PSA. Garzotto also stresses the size of the prostate has to be taken into account when measuring PSA. "What we worry about is which men may have high-grade cancer. Now we can prescribe a second biopsy for a few months later. We know that this is a judicious use for a biopsy," Garzotto said. Besides identifying which men may have a deadly form of prostate cancer this new finding could also reduce the rate of overtreatment, unnecessary biopsies and overdiagnosis.

Prostate biopsies can cause patient anxiety, pain, bleeding and infection, and can lead to a significant increase in medical and non-medical costs to health care systems and patients.

This study is particularly meaningful because of the large sample size of patient cases, and it is longitudinal, which means researchers were able to study the patients for many years.

Prostate cancer is the most common cancer, excluding skin cancer, and the second leading cause of cancer-related death in men in the United States. It is estimated that there will be 218,890 new cases diagnosed in 2007, and 27,050 men will die from prostate cancer this year in the United States.

More than 1 million prostate biopsies are performed each year. Of those, only about 25 percent test positive for cancer. However, another 25 percent are given a false negative, meaning that no cancer is detected even when later it is found that the patient does have cancer.

Prostate cancer less likely to spread when treated with higher dose of radiation

Fri, 24 Nov 2006 23:46:24 PST

( from http://www.rxpgnews.com ) New research suggests that men with prostate cancer who choose radiation therapy should seek treatment centers that will offer high-dose radiation. A new study from Fox Chase Cancer Center finds that higher doses of 74 to 82 Gray (Gy) greatly reduce the risk that the cancer will spread later--even 8-10 years after treatment.

"There is a comprehensive body of evidence demonstrating that prostate cancer treated with higher doses of radiation is less likely to grow back in the prostate or cause a rising PSA, and now, we know it is also less likely to spread later to other parts of the body," explained Peter Morgan, M.D., a resident in the Radiation Oncology Department at Fox Chase Cancer Center.

Generally, treatment centers that offer 3D conformal radiation therapy or a newer system of radiation delivery called IMRT (intensity modulated radiation therapy) treat men with the higher levels of radiation shown in this study to prevent the cancer's spread.

Morgan said that no published data from prospective randomized trials have shown a significant reduction in distant metastasis with higher radiation dose, likely because patients have not been followed for long enough to see the reduced of late-wave of metastasis. The current study shows that the risk of cancer spreading 8-10 years after treatment is lower when doses >74 Gray of radiation are given.

When asked how more radiation to the prostate protects the rest of the body from the cancer, Dr. Morgan replied, "That's what is so important about this work. We believe that the late wave of distant metastasis is due to the persistence of cancer in the prostate itself, which subsequently seeds tumor cells to other parts of the body. Because higher dose radiation more effectively kills cancer in the prostate, the source for future metastases is eliminated."

From 1989 to 1999, 667 men with intermediate- to high-risk prostate cancer were treated consecutively with 3D conformal radiation therapy. The outcomes of men who received less than 74 Gy, 74-75.9 Gy and greater than 76 Gy were compared. These groups had a median follow-up of 84, 84 and 65 months, respectively. The 10-year rate of the cancer spreading outside of the prostate (distant metastasis) was 16 percent for radiation doses less than 74 Gy, 7 percent for 74-75.9 Gy, and 3 percent for greater than 76 Gy.

Morgan said, "At our institution the policy for several years has been to treat prostate cancer to a dose of 76 to 80 Gy using IMRT. This study confirms that we are doing the right thing."

Gene therapy study takes aim at prostate cancer

Tue, 26 Sep 2006 22:40:37 PST

( from http://www.rxpgnews.com ) Researchers at Baylor College of Medicine (BCM) are hoping a new gene therapy that takes a gene called RTVP-1 directly into the prostate tumor will prove effective in preventing recurrence of the disease.

The first phase of the study is designed to test the safety of the treatment and determine the proper dosage of gene, said Dr. Dov Kadmon, professor of urology at BCM. It will be carried out in the department of urology at BCM as well as at Ben Taub General Hospital, The Methodist Hospital and Michael E. DeBakey Veterans Affairs Medical Center.

"We are treating patients who are scheduled for a prostatectomy (prostate removal) but who also have a high risk that their disease will recur (or come back)," said Kadmon. "The operation itself is highly successful in eradicating local tumors (in the prostate)."

The design of the study is simple, said Kadmon.

"One injection into the prostate that should take no more than 10 minutes, although patients will be monitored in a special unit of the hospital for 23 hours to make sure there are no side effects. After that, they come to the unit for a check-up once a week."

After about 30 days, the subjects undergo their surgery, which has already been scheduled, he said. He said the hope is that the gene therapy will reduce the risk that cancer will recur at or near the site of the tumor as well as in distant points in the body.

"We hope that by generating a systemic immune response, we are enabling the body to destroy prostate cancer cells that have moved elsewhere," he said. Kadmon and his colleagues plan to test six different doses of the gene.

The gene therapy involves attaching an inactivated adenovirus (related to viruses that cause respiratory infections) to the RTVP-1 gene. As the virus infects the tumor cells, it will introduce the gene into the cells as well. (RTVP stands for related to testes-specific, vespid and pathogenesis proteins.) The RTVP-1 gene was isolated in the laboratory of Dr. Timothy Thompson, also a professor of urology at BCM.

As Thompson began to study the gene, he found that it was a target for a tumor suppressor gene called p53, which is a major controller of cell activity in prostate and other cancers. He found that the human form of the gene is normally present in benign prostate or low grade tumor but is lost as the tumors become more malignant. "This characterized it as a tumor suppressor gene that is active in the prostate," said Kadmon.

When the gene is introduced into the tumors of animals lacking RTVP-1, it suppresses the formation of new blood vessels. It causes what is known as "apoptosis" or programmed cell death in prostate cancer cells and also activates the immune system to fight cancer cells.

"We are proceeding carefully, step-by-step," said Kadmon. He said they do not think the study presents a significant risk.

They will inject the virus-gene compound directly into the prostate. While there is a risk of infection with the injection, he said patients will receive antibiotics. Most patients will have some fever after the injection, but it can probably be handled with Tylenol.

Doctors will monitor patients after their surgery to determine the effect of the gene therapy on their disease.

Pain associated with prostatic biopsy is related to the site biopsied

Fri, 15 Sep 2006 03:01:37 PST

( from http://www.rxpgnews.com ) Researchers at Mayo Clinic have evaluated the major sources of pain for some men during in-office prostate biopsy and an anesthetic method that can best lessen it. Findings will be presented in two abstracts Thursday at the annual meeting of the North Central Section of the American Urological Association in San Diego.

Most prostate biopsies are performed on men who have abnormal digital rectal exams or abnormally elevated prostate-specific antigen (PSA) tests to evaluate the potential presence of cancer.

"Prostate biopsy evokes significant anxiety for some men due to anticipated pain associated with the procedure," says Richard Ashley, M.D., Mayo Clinic urology resident and lead study investigator. "We also noted that it seemed more men had pain with their prostate biopsies than we would have liked, and we wanted to make this procedure as comfortable as possible."

The researchers found about 16 percent of men who undergo prostate biopsy experienced a moderate or higher level of pain -- pain scores of 5 or more on a scale from 1 to 10. The injection of lidocaine to dull pain during the biopsy caused more pain than the insertion of the transrectal ultrasound probe, a small probe about the size of a cigar inserted into the rectum to produce images of the prostate gland during the biopsy. They also discovered that taking tissue samples in certain locations tested in a prostate biopsy were more likely to cause pain. Specifically, biopsy of the part of the prostate closest to the urethra, the prostate apex, was more painful than biopsy of the part closest to the bladder, the prostate base.

"We found we cannot predict who will have higher levels of pain at the time of a prostate biopsy simply based on the patient's history and features," says Dr. Ashley. "We discovered the location of biopsy was the most predictive of higher pain scores -- not age, body mass index, family history, presence of cancer, inflammation, whether a lump was palpable, or whether the prostate was large or small."

The investigators also found that anesthesia administered by direct infiltration of the prostate apex and the surrounding rectal tissues may provide better pain control during a prostate biopsy than other anesthetic methods.

"The prostate biopsy likely will never be a completely painless procedure, but it should be tolerable," says Dr. Ashley. "Patients should request that anesthetic be used at the time of a biopsy, and pain control should be the standard of care in a urologist's office. It does not take much time, and patients do benefit from this simple procedure to make the biopsy more tolerable. Patients should also be aware that different prostate locations biopsied are associated with more pain, and this may never be completely overcome by anesthetic. However, a complete and thorough sampling of the prostate gland is necessary to give the most accurate diagnosis to the patient."

In the study, Dr. Ashley and colleagues recruited 243 men scheduled to undergo in-office prostate biopsy in the Department of Urology at Mayo Clinic. The researchers randomly assigned the men to three different types of anesthetic: injection between the prostate base and seminal vesicle where the neurovascular bundle lies; intraprostatic injection into the substance of the gland, from the base to the apex; and injection at the prostate apex and surrounding rectal wall tissue. The biopsies were performed using a side-fire ultrasound probe and a biopsy gun. Six biopsies were performed on the right and left side of the prostate of each patient, focusing on the peripheral zone where most cancers occur.

The findings in this study need to be verified by other researchers in a larger study, according to
Dr. Ashley.

Admixture mapping reveals locus for prostate cancer risk

Tue, 22 Aug 2006 04:23:37 PST

( from http://www.rxpgnews.com ) Harvard Medical School researchers have identified a DNA segment on chromosome 8 that is a major risk factor for prostate cancer, especially in African American men. The paper appears in the August 21 electronic edition of the Proceedings of the National Academy of Sciences (also see PNAS's news tip below).

"This paper identifies a genetic risk factor that about doubles the likelihood of prostate cancer in younger African American men," says principal investigator David Reich, PhD, Harvard Medical School assistant professor of genetics with the HMS Department of Genetics and the Broad Institute. "This finding may explain why younger African Americans have an increased risk for prostate cancer than do other populations--and may also explain why this increased risk in African Americans attenuates with older age."

"This is one of the first genetic risk factors found that is responsible for an appreciable fraction of sporadic prostate cancer cases, particularly for the African American population," says lead author Matthew Freedman, Harvard Medical School instructor of medicine at the Dana-Farber Cancer Institute and the Broad Institute "Interestingly, we found that this region also confers risk for prostate cancer for diverse ethnic groups. The actual gene, however, remains to be identified."

The researchers used their newly developed method of "admixture mapping" to screen through the genome in African Americans (who have both African and European ancestry), searching for the segments where individuals with disease have more of one ancestry than the average. The key epidemiological fact is that prostate cancer occurs approximately 1.6-fold times more often in African Americans than in other populations. This prompted the hypothesis that there is a genetic risk factor for prostate cancer that occurs at higher frequency in African than in other populations, and that can be found by searching for a region where the proportion of African ancestry is higher than the genome average.

Reich, Freedman and their colleagues studied 1,597 African Americans with prostate cancer. They found a section of the genome in the patients that had much more than the average proportion of African ancestry, rising from 78 percent to about 85 percent. The risk factor is localized to a tiny fraction (about a thousandth) of the genome, a section on chromosome 8 containing just 9 genes.

A particularly exciting aspect of this work is that in May a separate research team also identified a genetic variant occurring within the same region, which increases risk for prostate cancer. The study by Reich and colleagues makes two additional advances. One important result is that the genetic risk factor is more important for individuals with younger age. Second, they show that the specific genetic variant reported in the earlier paper can explain only at most a small fraction of the increased risk to African Americans. Thus, major unidentified risk factors remain to be found.

A whole genome analysis has revealed a section on chromosome 8 as significantly associated with African-American's increased risk to prostate cancer. African Americans have about a 1.6 higher risk of developing prostate cancer than European Americans; at least part of this difference is likely a result of genetic factors. Taking advantage of recent advances, David Reich and colleagues used admixture mapping to try and find these factors. The concept of admixture mapping is to scan the genes of mixed ancestry populations (such as African Americans, descended from Africans and Europeans over the last 15 generations), searching for regions where the proportion of DNA inherited from one side is unusual. The authors found that a 3.8 million base region of chromosome 8, termed 8q24, substantially increased prostate cancer risk in men who inherited the African ancestry. Interestingly, this increase was greater in men diagnosed before the age of 72, correlating with observations that prostate cancer risk in African Americans attenuates with age. This same region, which contains 9 known genes, was recently identified by linkage analysis. However, the authors found their results cannot be explained by the two genes proposed in the other analysis; therefore, the major risk gene(s) for prostate cancer remain unidentified.

Admixture mapping entails scanning the genes of mixed ancestry populations to find regions where the proportion of DNA inherited from either ancestral side is unusual compared to the genome-wide average. This technique could be useful in uncovering risk variants, although it has only recently become practical. Matthew Freedman et al. have now applied admixture mapping to find genes for prostate cancer, taking advantage of its markedly increased incidence rates in African American men. Their analysis of 1,597 cancer cases and 873 controls revealed a 3.8 Mb section of chromosome 8, termed 8q24, that contributes to an increased cancer risk in African Americans with African (as opposed to European) ancestry at this region. There is also a highly significant association between risk and age at 8q24, which correlates with epidemiology studies that show that the elevated incidence of prostate cancer in African Americans compared with other populations attenuates with age. A recent linkage analysis also highlighted a risk association in this region, but Freedman et al. report that the previously described alleles only explain a fraction of the admixture signal; therefore 8q24 still contains a major unidentified risk gene for prostate cancer.

Diet modification and stress reduction may attenuate progression of prostate cancer

Tue, 15 Aug 2006 22:17:37 PST

( from http://www.rxpgnews.com ) Statistics say that one out of six American men will develop prostate cancer and more than a third of them will experience a recurrence after undergoing treatment, putting them at high risk to die of the disease. In a recent study published in SAGE publication's Integrative Cancer Therapies, Dr. Gordon A. Saxe and colleagues at the Moores Cancer Center and School of Medicine at the University of California, San Diego found that diet changes, reinforced by stress management training, appeared to be effective in slowing or halting the spread of this deadly cancer.

The study, published in the September issue of Integrative Cancer Therapies, focused on the change in the levels of prostate-specific antigen (PSA), an indicator of the cancer, in response to a plant-based diet and stress reduction. Patients were taught to increase consumption of plant-based foods such as whole grains, cruciferous and leafy green vegetables, beans and legumes, and fruit, and to decrease the intake of meat, dairy products, and refined carbohydrates. They were also provided with stress management training, which incorporated meditation, yoga and Tai Chi exercises. The plant-based diet and stress reduction were effective in significantly reducing the PSA rate, indicating a reduction in the rate of progression of the prostate cancer.

"The magnitude of effect of these findings is the strongest observed to date among dietary and nutritional interventions in this patient population," states Dr. Saxe, assistant professor of Family and Preventive Medicine. "These results provide preliminary evidence that adoption of a plant-based diet, in combination with stress reduction, may attenuate disease progression and have therapeutic potential for management of recurrent prostate cancer."

The article "Potential Attenuation of Disease Progression in Recurrent Prostate Cancer Progression With Plant-based Diet and Stress Reduction" can be accessed at no-charge for a limited time on the SAGE Publications' Integrative Cancer Therapies web site at http://ict.sagepub.com/cgi/reprint/5/3/206.

Prostatic Irradiation Doesnt Lead To Any Appreciable Increase in Rectal Cancer Risk

Tue, 04 Jul 2006 00:11:37 PST

( from http://www.rxpgnews.com ) Men who receive radiation therapy for prostate cancer are not at any appreciable increased risk of developing rectal cancer compared to those not given radiation therapy, according to a new study published in the July 1, 2006, issue of the International Journal of Radiation Oncology*Biology*Physics, the official journal of ASTRO, the American Society for Therapeutic Radiology and Oncology.

This year, 235,000 American men will be diagnosed with prostate cancer. The main ways of dealing with the disease are radiation therapy, surgery and watchful waiting each of which has its benefits and disadvantages. Researchers have hypothesized that one disadvantage of using radiation to kill the cancer cells in the prostate is that it might also make men more likely to develop cancer in the nearby rectum.

In this study, doctors in Canada evaluated the records of 237,773 men who had prostate cancer. Of them, 33,841 received radiation therapy, 167,607 had their prostate removed surgically and 36,335 received neither treatment. On an initial simple evaluation, doctors found that rectal cancer developed in 243 men who received radiation (0.7 percent), 578 men treated with surgery (0.3 percent), and 227 of the men given neither treatment (0.8 percent). Once doctors had adjusted for the age differences between all the men in the irradiated and non-irradiated groups, they could not find any significant increased risk of rectal cancer in the irradiated men compared to those not given radiation therapy.

Rectal cancer from other causes is frequent enough in our population to obscure any small incidence of radiation-induced cancer. I hope that the results of this study will help men with prostate cancer and their families put these risks in their proper perspective, and not let their concerns about rectal cancer dissuade them from choosing radiation therapy as a treatment for this disease, said Wayne S. Kendal, M.D., Ph.D., an Associate Professor in Radiation Oncology at the Ottawa Hospital Regional Cancer Centre in Ontario, Canada.

Pomegranate Juice Slows PSA Acceleration Rate

Sat, 01 Jul 2006 17:32:37 PST

( from http://www.rxpgnews.com ) Pomegranate juice packs a punch on prostate cancer that prolongs post-surgery PSA doubling time, drives down cancer cell proliferation and causes prostate cancer cells to die, according to a study published in the July 1 issue of Clinical Cancer Research.

Researchers at the Jonsson Cancer Center at UCLA reported that patients with recurrent prostate cancer who drank pomegranate after surgery or radiation treatment saw their PSA blood content levels double after about 54 months. By comparison, PSA levels in the same patients prior to drinking the daily doses of eight-ounce pomegranate juice accelerated more quickly, doubling their PSA levels in only 15 months.

PSA, or prostate specific antigen, is a protein marker for prostate cancer. The faster PSA levels increase in the blood of men after treatment, the greater their potential for dying of prostate cancer.

The velocity of the increase in PSA is decreased by 35 percent among those who drank the pomegranate juice, said Allan Pantuck, M.D., associate professor, Department of Urology, David Geffen School of Medicine, UCLA, and lead author of the paper.

We are hoping that pomegranate juice offers a novel strategy for prolonging the doubling time in men who have been treated for prostate cancer, Dr. Pantuck added.

According to the study, sera from patients after treatment yielded a net decrease of almost 30 percent in the numbers of prostate cancer cells raised in culture. Similarly, cultured sera from these patients decreased cell proliferation by 12 percent, compared to cells grown with sera from the men taken prior to initiation of the pomegranate treatment program. In addition, treated sera induced 17 percent more programmed cell death, or apoptosis, than sera from the men prior to treatment.

Additional exploratory experiments conducted by Dr. Pantuck and his colleagues examined antioxidant characteristics of the fruit juice.

Pomegranate is high in antioxidants, and there is good evidence that inflammation plays an important role in prostate cancer, he said.

Dr. Pantuck and his colleagues detected a 23 percent increase in nitric oxide sera content from patients after they began their daily pomegranate regimen. These studies were conducted in the UCLA laboratory of Louis Ignarro, Ph.D., the Nobel laureate who contributed key scientific findings to define the role of nitric oxide in health and disease.

As with vitamin C and other antioxidants, ellagic acid a primary antioxidant in pomegranate juice works to quench molecules that oxidate, or add oxygen, to cellular and circulatory proteins and fats, altering their biological function.

By quenching oxidative species with antioxidants, you are basically preserving circulating nitric oxide, so it can have a greater biologic effect, Dr. Pantuck said. By decreasing the amount of free radicals, you are probably decreasing the circulating factors that are destroying nitric oxide.

While their findings on nitric oxide, cell proliferation and apoptosis served as exploratory endpoints, Dr. Pantuck stressed that clinical trials with more precise design are necessary to confirm the biological role the fruit plays in prolonging or preventing recurrence of prostate cancer in men.

We dont believe we are curing anyone from prostate cancer, he said. In our initial trial, although a third of patients experienced a decrease in their PSA during the study, nobodys PSA went to zero.

The PSA doubling time, however, was longer. For many men, this may extend the years after surgery or radiation that they remain recurrence free and their life expectancy is extended. They may be able to prevent the need to undergo additional therapies, such as radiation, hormonal or chemotherapies.

Pomegranate juice could kill cancer cells

Sat, 01 Jul 2006 14:56:37 PST

( from http://www.rxpgnews.com ) Drinking an eight ounce glass of pomegranate juice daily could slow the progress of prostate cancer, minimise cell damage and could also kill cancer cells, finds a new study.

Researchers led by Allan Pantuck at the University of California, Los Angeles, studied 50 men who had undergone surgery or radiation treatment for prostate cancer - but had shown signs that the disease was rapidly returning.

The presence of prostate cancer cells is monitored by measuring levels of a chemical they produce called prostate-specific antigen (PSA). The researchers measured how long it took for PSA levels to double in individual patients - a short doubling time indicates that the cancer is progressing quickly.

The average doubling time is about 15 months, but in patients who drank pomegranate juice, this increased to an average of 54 months.

Some patients continued to show suppressed PSA levels after more than three years, even though they were receiving no treatment apart from drinking pomegranate juice, said Pantuck.

The researchers added that the effect may be so large that it may help older men outlive the disease.

'There are many substances in pomegranate juice that may be prompting this response,' said Pantuck.

'We are hoping we may be able to prevent or delay the need for other therapies usually used in this population such as hormone treatment or chemotherapy, both of which bring with them harmful side effects,' added Pantuck.

Pomegranates have been linked to many health benefits. It contains a cocktail of chemicals including isoflavones, which are believed to play a role in cancer cell death.

Previous research, conducted through tests on mice, has indicated that pomegranate juice could have a beneficial effect on prostate cancer.

Early estrogen exposure leads to later prostate cancer risk

Thu, 01 Jun 2006 12:52:37 PST

( from http://www.rxpgnews.com ) A study in the June 1 issue of Cancer Research presents the first evidence that exposure to low doses of environmental estrogens during development of the prostate gland in the male fetus may result in a predisposition to prostate cancer later in life.

The study, done in an animal model, also demonstrates how the predisposition may arise, and a way to identify those at risk.

Man-made compounds that can mimic the hormone action of estrogens (xenoestrogens) are widespread in the environment. One of these agents is bisphenol A (BPA), used in the manufacture of plastics and epoxy resins. The United States alone produces over 1.6 million pounds of BPA annually. BPA, which can also leach from plastics when heated, turns up in human blood and in placental and fetal tissues in even higher concentrations.

In this study, a research team led by Dr. Gail Prins of the University of Illinois at Chicago and Dr. Shuk-Mei Ho of the University of Cincinnati exposed rats to low doses of estradiol, a natural estrogen, or to BPA during the developmental period corresponding to the second and third trimester of human pregnancy. They found that this early exposure predisposed male rats to precancerous lesions of the prostate in old age.

"Most remarkably, early BPA exposure sensitized the prostate to precancerous lesions brought on by exposure of the adult animal to elevated estradiol," said Prins, professor of urology at UIC and senior author of the study. "This is highly relevant to people, because relative estradiol levels increase in aging men as a result of their increased body fat and declining testosterone levels."

The doses of estradiol and BPA used in the study were similar to levels found in human serum; in the circulation of some pregnant women; and in the fetus. Transfer of BPA from mother to fetus has been reported, and levels in male fetuses have been shown to be higher than those of female fetuses.

The researchers were able to demonstrate that early estrogen or BPA exposure permanently changed the methylation, or tagging, of specific stretches of DNA in the neonate's prostate cells, a phenomenon referred to as epigenetic reprogramming. In epigenetic reprogramming, gene expression is altered without changing DNA sequences or content. Several of the epigenetically altered sites turned out to be in important genes that regulate cellular functions.

The researchers conclude that exposure to environmental estrogens, such as BPA, or natural estrogens affect the pattern of gene expression in the prostate during development, and in so doing promote prostate disease with aging.

One of the altered genes, phosphodiesterase 4 (PDE4D4), was examined in greater detail. The researchers found that the methylation of PDE4D4 can permanently change its pattern of expression in the prostate. This gene should normally shut down in adult life, but after early exposure to estradiol or BPA, the exposed animals' prostates continued to express it at high levels. Similar high levels due to methylation of the gene were found in prostate cancer cells but not in normal cell lines.

Because the methylation marks of epigenetic reprogramming were found before any disease was observed, the methylation may be useful as a way to identify men at higher prostate disease risk, Prins said, which may have resulted from early exposure to endocrine disruptors.

"These findings are true for an animal model, and application to human prostate disease will await future studies," the authors concluded. Ho is first author of the study and professor and chairman of environmental health at the University of Cincinnati.

JHDM2A enzyme induced H3K9 demethylation offers new look at male hormone regulation

Sun, 07 May 2006 15:14:37 PST

( from http://www.rxpgnews.com ) For the second time in less than a year, University of North Carolina at Chapel Hill scientists have purified a novel protein and have shown it can alter gene activity by reversing a molecular modification previously thought permanent.

The findings, published in the journal Cell, also show that the new protein plays a role in gene activation mediated by androgen receptor, a protein that responds to androgen hormones. In this regard, the novel protein may figure in the development of prostate cancer.

Androgens, particularly testosterone and dihydrotestosterone, determine male secondary sex characteristics and stimulate prostate cell growth. Lowering androgen levels usually can make prostate cancers shrink or grow more slowly.

In the study, the researchers said the new protein called JHDM2A, like the protein they reported on in the journal Nature in December 2005, is able to remove a methyl group from histone H3, one of four histone proteins bound to all genes.

"Human genes are so tightly compact within the nucleus that if the DNA of a single cell were unwound and stretched, it would be a line of about two meters in length. Histones are necessary to package the DNA so that it fits inside a cell's nucleus," said senior author Dr. Yi Zhang, professor of biochemistry and biophysics at UNC's School of Medicine and the university's first Howard Hughes Medical Institute investigator.

Zhang also is a member of the UNC Lineberger Comprehensive Cancer Center.

Because histones are so intimately associated with DNA, even slight chemical alterations of these proteins can have profound effects on nearby genes. Depending on their precise location and how many methyl groups are added, the presence of alterations can either turn on or turn off a gene.

In the study, Zhang learned that the JHDM2A specifically removes methyl-groups from lysine 9 of histone H3.

"The important thing is that H3K9 demethylation has been linked to transcription silencing, turning genes off. So that led us to pay attention to this protein's role in reversing whatever function K9 methylation might have," Zhang said.

In their experiments, the researchers learned that consistent with reversing a marker of gene silencing (H3K9 methylation), the protein functions as a co-activator in this case, a co-activator for the androgen receptor target genes.

Using human tissue cultures, including prostate cells, Zhang and his colleagues found that over-expression of JHDM2A greatly reduced H3K9 methylation level and led to upregulation, or switching on, of androgen receptor target genes. In contrast, when methylation was increased, the gene was silenced switched off.

It remains unclear for how many different human genes JHDM2A is a primary regulator. According to Zhang, the new findings indicate that the protein will provide another tool to enlist in studies of gene expression regulation.

"Given the androgen receptor link, we're now trying to identify the downstream target genes, as well as its role in prostate cancer," he said.

"Theoretically, this protein is a very important tool for gene expression studies. Practically, it provides a potential target for prostate cancer because of its enzymatic activity. And it is enzymatic activity that's the favorite target of drug development."

What is the appropriate age to stop prostate cancer screening?

Wed, 03 May 2006 00:45:37 PST

( from http://www.rxpgnews.com ) Screening for prostate cancer in older men has been problematic. While this form of cancer can be fatal, it often progresses so slowly that men are more likely to die from some other disease. Aggressive treatments such as radical prostatectomy or radiation therapy may eradicate the cancer but have negative effects on quality of life. More conservative treatments may preserve quality of life, but may not be appropriate for those cases where the disease is progressing more quickly. In the face of these uncertainties, what is the appropriate age to stop screening?

Although guidelines suggest that men 75 years or older may not benefit from screening, surveys continue to show high rates of screening in this population. Since most screening and treatment trials for prostate cancer have systematically excluded older men, there are no well-characterized data about survival and quality-of-life issues.

In a population-based cohort study published in the May issue of The American Journal of Medicine, researchers followed 465 men aged 75 to 84 who had been diagnosed with clinically localized prostate cancer in 1994 or 1995. Of those patients, 175 received aggressive treatment (surgery or radiation therapy) and 290 received hormone therapy or no treatment. The authors evaluated health-related quality of life (HRQOL) outcomes and survival 2 years after the original diagnosis. Survival was also evaluated 7 years after diagnosis.

Writing in the article, Richard M. Hoffman, MD, MPH, of the Medicine Service, New Mexico VA Health Care System and the University of New Mexico Cancer Research and Treatment Center, concludes, "Aggressive treatment minimally reduced the risk of dying from prostate cancer; disease specific survival, however, was relatively high in both groups because most deaths were from other causes. However, by 24 months following diagnosis, men who received aggressive treatment had suffered more urinary and bowel dysfunction and were more bothered by sexual dysfunction. General health and physical function were higher for aggressively treated men but this was likely due to residual selection bias. Our results reinforce concerns that men 75 years and older may not benefit from prostate cancer screening because they may suffer adverse outcomes from aggressive treatment of localized disease."

High cholesterol may contribute to prostate cancer

Wed, 12 Apr 2006 18:10:37 PST

( from http://www.rxpgnews.com ) High cholesterol may contribute to the development of prostate cancer although further studies are needed to confirm the results, say scientists.

Prostate cancer strikes about one in six US men. The risk factors for prostate cancer are age, ethnic background and family history.

But researchers led by Francesca Bravi from the Mario Negri Institute for Pharmacological Research in Milan, Italy, found some evidence of the link between cholesterol and prostate cancer, reported the online edition of New Scientist.

Bravi and colleagues reviewed the medical files of nearly 3,000 men under the age of 75 from four different regions of Italy. This included 1,294 men who had prostate cancer and 1,451 men without the disease.

They asked the participants if they had a history of high cholesterol and found that 22 percent of the men with prostate cancer suffered from high cholesterol, compared with 16 percent of the men who did not have these lethal tumours.

After adjusting for other factors such as family history of prostate cancer and smoking, the team found that those with the disease were 50 percent more likely to have high cholesterol than their counterparts who kept their cholesterol levels under control.

However, Bravi said while it was likely that high cholesterol may contribute to the development of prostate cancer, the study did not firmly establish the causative link.

He noted that the body uses cholesterol to make hormones known as androgens, which influence prostate tissue. A surplus of cholesterol may lead to unbalanced production of the hormone.

While cutting levels of cholesterol is known to be good for heart health, the researchers observe that it is too soon to corroborate that the same applies to prostate health. "Further studies are needed to confirm the results of our investigation before any dietary recommendations can be given," Bravi said.

Human infections documented with a native rodent retrovirus

Fri, 31 Mar 2006 12:50:37 PST

( from http://www.rxpgnews.com ) Howard Hughes Medical Institute researchers and their colleagues have discovered a new retrovirus in humans that is closely related to a cancer-causing virus found in mice. Their findings describe the first documented cases of human infection with a retrovirus that is native to rodents.

The researchers discovered the virus in patients with a rare type of prostate cancer. The patients in the study have a genetic mutation that compromised some of their natural defenses against viral infection. Thus, the researchers said their discovery raises the possibility that increased susceptibility to viral infection may play a role in development of some cancers. However, they emphasized that their findings by no means implicate the virus, dubbed XMRV, in causing prostate cancer. The virus may well have flourished as a result of the failure of the defense mechanism; and other factors such as chronic inflammation may play a more direct role in the cancer.

The discovery of the new virus was made by an interdisciplinary research team led by Robert Silverman of Cleveland Clinic and HHMI investigators Joseph DeRisi and Don Ganem, both at the University of California at San Francisco. The search for the new virus began when Silverman and his colleagues provided samples of a rare familial prostate cancer in which the viral-defense gene, RNASEL, had been mutated in a specific way. This mutation compromised the function of the enzyme produced by RNASEL, which normally shreds viral genetic material. Infected cells carrying the shredded viral genetic material are usually targeted for destruction by the immune system. While some scientists believe that such vulnerability to viral infection is connected to prostate cancer in these rare cases, others have presented evidence contesting that theory.

To screen for viruses in the prostate tissue samples, DeRisi and Ganem used the Virochip, which was invented by DeRisi and his colleagues. The Virochip consists of a microarray of some 20,000 characteristic gene sequences called oligonucleotides representing a vast array of known viruses. The oligonucleotides are deposited as tiny spots on a small glass chip.

To detect viruses from tissue samples, the researchers isolated genetic material from each sample and tagged the genetic material with a fluorescent tracer. They then applied the fluorescently tagged genetic material to the microarray chip. Since genes tended to adhere to those with a complementary genetic sequence, any viral gene sequences in the sample would attach themselves to corresponding viral sequences on the chip. The telltale fluorescence on spots on the chip signaled the presence of viral genetic material in the sample.

Although the Virochip contains only sequences from known viruses, DeRisi said it can also detect new viruses because they invariably contain sequences that have been conserved in their evolution from related viruses.

The initial screen of the RNASEL-mutant prostate cancers revealed the presence of a genetic sequence that closely resembled that of a mouse virus called murine leukemia virus (MuLV). Murine leukemia virus is known as an endogenous virus because it normally exists as an integrated part of the mouse genome, rather than as independent, infective particle. The RNA is then reverse transcribed into DNA that is integrated into the DNA of the host cell the virus is infecting.

When the researchers isolated and sequenced the genome of the virus, they found that it was a xenotropic virus - one that can only grow in foreign cells other than mouse cells. Thus, they named the virus, Xenotropic MuLV-related virus, or XMRV.

According to DeRisi, the Virochip made it possible to analyze these samples without preconceived biases about what viruses might be present. We would never have looked for this class of virus if it wasn't for the virus chip.

Importantly, the researchers found that prostate cancers in which both copies of the RNASEL gene were crippled by mutation showed much more frequent XMRV infection than did those cancers that still had one normal copy of the RNASEL gene.

This link between the virus and RNASEL is the second finding that is important and is firmly established in this study, noted Ganem. We don't see the infection in people who don't have the RNASEL mutation, which suggests strongly RNASEL is an important part of the defense against retroviral infection. DeRisi pointed out that detailed comparison of samples of the virus between people found that - although all were XMRV - they showed tiny genetic variations. Ganem cautioned that any link between XMRV and prostate cancer is tenuous at best. First, the genetic variant we studied occurs in familial clusters that constitute only a very small sliver of prostate cancers, he said. And secondly, there are many reasons to believe that the virus might not relate to prostate cancer.

For example, he pointed out, analysis of prostate tissue by Silverman and his colleagues indicated that the virus appears only in a small percentage of connective tissue cells, called stromal cells, rather than in the tumors themselves. So, one interpretation could be that the infection is entirely incidental to prostate cancer, said Ganem. Clearly XMRV is not a classic oncogenic virus.

Nevertheless, said Ganem, an indirect link to cancer cannot be ruled out, since in cancer research these days, there is a lot of interest in the stroma as the soil in which cancer arises. He added that the chronic inflammation from infection of stromal tissues may play a role in triggering such cancers.

This initial finding raises many questions. How is the virus passed from person to person? And are people the natural reservoir of this virus, or is it some other organism?

DeRisi and Ganem said they are planning studies to explore whether XMRV is restricted to prostate cancers or whether it is more widespread in the body and in other segments of the human population.

Alterations in DNA methylation is a better indicator of prostate cancer

Tue, 28 Mar 2006 21:15:37 PST

( from http://www.rxpgnews.com ) Researchers at Mayo Clinic have narrowed the search for effective prostate cancer biomarkers (genetic variations that point to a specific disease or condition), identifying changes in the expression of genes of the whole genome closely correlated to prostate cancer development and progression. They also showed that DNA hypermethylation (DNA modification without changing sequence) plays a significant role in these processes. Results of their study were published in the Feb. 15 issue of Clinical Cancer Research.

"This is good news in an area where our ability to diagnose and predict has previously been less than stellar," said Krishna Donkena, Ph.D., Mayo Clinic urologic researcher. "Our only tool is the PSA test, which has little predictive value. These findings move us much closer to a more accurate test."

The search to identify biomarkers that can be translated into affordable and effective medical tests can be complicated. Prostate cancer causes differential expression of hundreds of different genes, each potentially an indicator of whether a man may get the disease, or already has it. They also may be used to provide information on the development of the cancer, without the need for a painful tumor biopsy.

When seeking to narrow their search to a manageable level, the researchers analyzed 32 cancerous and eight benign patient-tissue samples using genome microarrays representing 33,000 human genes. The information they gleaned from this analysis allowed them to identify 624 differentially-expressed genes between cancerous and benign tissue. They validated these findings in the original 40 tissue samples as well as in 32 additional samples (20 cancerous, 12 benign). The results showed eight genes with significant under-expression and three with significant over-expression, strongly implicating them in prostate cancer development and progression.

Over the years, research has shown that DNA methylation is commonly linked to the development and progression of cancers. This epi-genetic alteration results in silencing or seriously inhibiting gene expression, which in turn lessens the body's ability to defend against cancer. Current research has not done enough to discover ways to convert this information into a useful medical test, in large part due to the limited number of genes that have been thoroughly studied, and their insufficient sensitivity and specificity (probability of getting a true positive or true negative) for prostate cancer detection.

Dr. Donkena's team looked at 62 cancerous and 36 benign tissue samples to assess the degree of methylation in the three previously identified under-expressed genes, comparing two known methylated genes. They determined that one gene, PDLIM4, had hypermethylation that could serve as an effective sensitivity marker, accurately detecting prostate cancer 95 percent of the time. The researchers further determined that the combined measurement of a previously known gene, GSTP1, and PDLIM4 improved the detection rate to 98 percent.

Prostate cancer is the second leading cause of cancer death for men in the United States, exceeded only by lung cancer. The sooner a cancer can be diagnosed, the better treatment outcomes will be, so Dr. Donkena and her colleagues are constantly looking for ways to predict who will get prostate cancer, as well as to find better ways to diagnose early or even prevent this disabling and often fatal disease. "We hope that in addition to being a valuable diagnostic and prognostic tool, our discoveries about these genes will help us develop new treatments for prostate cancer," she said.

Prostate treatment decisions based on perception more than fact

Mon, 27 Mar 2006 16:22:37 PST

( from http://www.rxpgnews.com ) Men with prostate cancer generally make treatment decisions based on differences in the information they receive rather than their own preferences, according to a new review. Published in the May 1, 2006 issue of CANCER, a peer-reviewed journal of the American Cancer Society, the review of studies in prostate cancer decision making suggests that a lack of medical evidence and consistent, comprehensive messages about therapeutic options compel men to turn to a wide variety of popular and biased sources, which influence their decision. This approach often results in treatments that do not generally reflect patients' goals.

Despite new treatment options for prostate cancer, there is little evidence-based consensus in the oncology community about the most efficacious treatment. Newly diagnosed patients must still balance existing information about risks and benefits of available therapies with their own treatment objectives. Studies have shown that prostate cancer treatment varies not only among men in general but also by race and ethnicity, suggesting that the guidance patients receive is variable and confusing, and plays a part in their decision-making. Steven B. Zeliadt, Ph.D., M.P.H., of the Fred Hutchinson Cancer Center in Seattle and colleagues synthesized data from other studies to examine how and why men with prostate cancer make treatment decisions.

The review of current literature shows that cancer eradication or control was the foremost objective of treatment for men. Minimizing side effects ultimately played a minor role in decision making. However, studies report a gap between patient treatment objectives and the evidence supporting the efficacy of the treatment chosen. Men's concerns about controlling "the cancer" correlated directly with the aggressiveness of the treatment they chose, regardless of actual disease severity. Yet, in choosing treatment, patients did not consistently rely on scientific evidence of a therapy's efficacy to control disease or prolong life. As few as one in four patients in one study relied on evidence of a treatment efficacy for their decision.

Physicians and family, as well as race and culture may affect patients' decisions, but the degree of their respective influence varies in the literature and is often poorly measured, according to the review. Notably, physicians tended to present therapies in ways that were both confusing and dismissive of patient concerns about risks. This either biased patients' decisions or turned patients to other sources of information.

Finally, studies fail to show how and if patients actually critically analyze the quality of information they receive. It is very likely, the authors add, that patients "have significant limitations in their ability to identify biased information, as well as their ability to weigh complex information about the outcomes that are important to them."

"The perceptions of treatment efficacy related to cancer control far outweigh available supporting evidence, and most patients appear to select a prostate cancer treatment primarily based on its perceived ability to control the tumor," conclude the authors.

Older men with early prostate cancer survived longer with treatment vs. observation

Sun, 26 Feb 2006 17:30:37 PST

( from http://www.rxpgnews.com ) A new study shows older men with early stage prostate cancer survive longer if they are treated versus not being treated in favor of the "watchful waiting" approach advocated by many physicians for older men with other health problems. In addition, the study revealed a survival benefit for men treated with radiation therapy making it the first study to demonstrate a survival advantage in an older population.

The study examines survival data of more than 48,606 men between 65 and 80 years old who survived at least one year after a diagnosis of localized prostate cancer (cancer that has not spread beyond the prostate).

Since the advent of the PSA (prostate-specific antigen) blood test about 20 years ago, many more cases of prostate cancer have been diagnosed at earlier stages.

"Some prostate cancers grow so slowly that they never become life-threatening, especially in elderly men who may die of other causes before the cancer causes problems," explained Wong. "But other men develop complications and die from their cancer making the decision to treat quite difficult."

It remains unclear whether detecting early prostate tumors translates into an equivalent benefit of saving lives and whether the benefits of early detection outweigh the risks of complications from follow up diagnostic tests and cancer treatments.

The cases examined in this study were diagnosed between 1991 and 1999. The men ranged from 65 to 80 years old at diagnosis. Median age at diagnosis was 72. A total of 34,046 men received treatment with either radiation therapy (19,948) or surgery--radical prostatectomy--to remove the prostate (14,098). The remaining 14,560 men were only observed (watchful waiting).

More than half the treated men were alive by the end of the study, with a median survival of 13 years. Median survival for the group receiving observation was about 10 years.

"This large, population-based study demonstrates a survival advantage for men treated with either radical prostatectomy or radiation therapy compared to observation," Wong said. "Eligible men should be considered for both treatment options."

Cabbage, cauliflower and turmeric please!

Tue, 17 Jan 2006 01:32:37 PST

( from http://www.rxpgnews.com ) Rutgers researchers have found that the curry spice turmeric holds real potential for the treatment and prevention of prostate cancer, particularly when combined with certain vegetables.
The scientists tested turmeric, also known as curcumin, along with phenethyl isothiocyanate (PEITC), a naturally occurring substance particularly abundant in a group of vegetables that includes watercress, cabbage, winter cress, broccoli, Brussels sprouts, kale, cauliflower, kohlrabi and turnips. "The bottom line is that PEITC and curcumin, alone or in combination, demonstrate significant cancer-preventive qualities in laboratory mice, and the combination of PEITC and curcumin could be effective in treating established prostate cancers," said Ah-Ng Tony Kong, a professor of pharmaceutics at Rutgers, The State University of New Jersey.

The discovery was announced in the Jan. 15 issue of the journal Cancer Research by Kong and his colleagues at Rutgers' Ernest Mario School of Pharmacy.

Prostate cancer is the second leading cause of cancer death in men in the United States, with a half-million new cases appearing each year. The incidence and mortality of prostate cancer have not decreased in past decades despite tremendous efforts and resources devoted to treatment. This is because advanced prostate cancer cells are barely responsive even to high concentrations of chemotherapeutic agents or radiotherapy.

The authors noted that in contrast to the high incidence of prostate cancer in the United States, the incidence of this disease is very low in India. This has been attributed to the dietary consumption of large amounts of plant-based foods rich in phytochemicals nonnutritive plant chemicals that have protective or disease-preventive properties.

Consequently, scientists have been investigating intervention options based on compounds found in edible and medicinal plants. They have had some success, and a majority of patients with prostate cancer are now combining the conventional therapies with these compounds as alternative, supplementary or complementary medications.

For Kong's study, researchers used mice bred so that their immune systems would not reject foreign biological material and injected the mice with cells from human prostate cancer cell lines to grow tumors against which the compounds could be tested.

"Despite convincing data from laboratory cell cultures, we knew little about how PEITC and curcumin would perform in live animals, especially on prostate cancer," Kong said. "So we undertook this study to evaluate how effective PEITC and curcumin might be individually and in combination to prevent and possibly treat prostate cancer."

The researchers injected the mice with curcumin or PEITC, alone or in combination, three times a week for four weeks, beginning a day before the introduction of the prostate cancer cells. They found the injections significantly retarded the growth of cancerous tumors. Using PEITC and curcumin in tandem produced even stronger effects.

The group went on to evaluate the therapeutic potential of curcumin and PEITC in mice with well-established tumors, and the results showed that PEITC or curcumin alone had little effect, whereas the combination of curcumin and PEITC significantly reduced tumor growth.

Speed of PSA increase is a better prognostic marker

Sat, 12 Nov 2005 20:02:38 PST

( from http://www.rxpgnews.com ) In the largest study of its kind to date, Mayo Clinic researchers report that prostate specific antigen (PSA) kinetics, both velocity and doubling time, can be used to predict disease progression and likelihood of death after radical prostatectomy surgery, suggesting that this could be used to guide treatment decisions.

"The level of PSA in the blood has less prognostic value than we previously thought, and we don't have another serum marker to help us," says Michael Blute, M.D., Mayo Clinic urologist and lead investigator of the study. "It was important for us to find other ways to look at PSA data and translate that into information that will save lives, and I believe we have done that."

Prostate cancer is the second most common cancer in men (skin cancer is first) and the second leading cause of cancer death in American men, exceeded only by lung cancer. This year, the American Cancer Society estimates 232,000 new cases of prostate cancer will be diagnosed. While one in six men will be diagnosed with prostate cancer in his lifetime, only one in 33 will die of it. However, because it causes disability and death, finding new strategies to better target treatments is an important public health goal.

Dr. Blute and his fellow researchers reviewed the records of 2,290 patients with multiple preoperative PSA measurements, as well as 5,176 patients with only one preoperative measurement, looking at the rate at which PSA increased in the body -- thought to indicate cancer growth. This was measured as both the PSA velocity (PSAV), the rate of increase in PSA levels over time, and the PSA doubling time (PSADT), a measure of how quickly PSA levels double. The researchers found that while PSAV is simpler to calculate, PSADT may be a better indicator of untreated prostate cancer.

Over an average follow-up period of about seven years, cancer spread or recurrence, and deaths from cancer were recorded. Biochemical progression was noted in 25.5 percent of the patients, clinical progression in 6.8 percent and cancer death in 1.8 percent. PSAV and PSADT both predicted progression and death. PSAV greater than 3.4 ng/ml yearly correlated to men being 6.54 times more likely to die than those with lower PSAV. PSADT quicker than 18 months correlated to the risk of death being 6.22 times higher than for those with longer PSADT.

"This provides valuable pretreatment prognostic factors for prostate cancer," says primary author Shomik Sengupta, M.D. "We hope that our work will help in the doctor-patient discussion and result in more informed decisions relating to observation, intervention and adjuvant treatment."

The study group consisted of patients who had undergone radical prostatectomy for prostate cancer between 1990 and 1999 at Mayo Clinic. Preoperative and postoperative PSA measurements were obtained from referring physicians and/or Mayo laboratory testing.

Pomegranate Juice to Combat Prostate Cancer

Tue, 27 Sep 2005 21:11:38 PST

( from http://www.rxpgnews.com ) Earlier research at Wisconsin and elsewhere has shown that the pomegranate, a fruit native to the Middle East, is rich in anti-oxidant and anti-inflammatory activity and is effective against tumors in mouse skin. In fact, pomegranate juice has higher anti-oxidant activity than do red wine and green tea, both of which appear promising as anti-cancer agents.

The UW research team aimed to find out if the extract from pomegranates would not only kill existing cancer, but help prevent cancer from starting or progressing. Using human prostate cancer cells, the team first evaluated the fruit extract's effect, at various doses, on those cells cultured in laboratory dishes. They found a "dose-dependent" effect - in other words, the higher the dose of pomegranate extract the cells received, the more cells died.

The research team then progressed to tests in mice that had been injected with prostate cancer cells from humans and developed malignancies. The 24 mice were randomly divided into three groups. The control group received normal drinking water, while the animals in the second and third groups had their drinking water supplemented with .1 percent and .2 percent pomegranate extract respectively. The results were dramatic: the mice receiving the higher concentration of pomegranate extract showed significant slowing of their cancer progression and a decrease in the levels of prostate-specific antigen (PSA), a marker used to indicate the presence of prostate cancer in humans. "Our study - while early -- adds to growing evidence that pomegranates contain very powerful agents against cancer, particularly prostate cancer," says lead author Dr. Hasan Mukhtar, professor of dermatology in the UW Medical School. The next step in the evaluation of pomegranates for cancer prevention and treatment is to conduct tests in humans, according to Mukhtar.

Additional information from wikipedia: Pomegranates are high in polyphenols, which are compounds that may help reduce 'silent inflammation' which is at the root of diseases such as cancer, heart disease, and diabetes. The most abundant polyphenols in pomegranate are hydrolysable tannins, particularly punicalagins, which have been shown in many peer-reviewed research to be the superior antioxidant responsible for the free-radical scavenging ability of pomegranate juice.

Many food and dietary supplement makers have found the advantages of using natural spectrum pomegranate extracts over the juice (no sugar, calories, or additives) as healthy ingredients in their products. As far as pomegranate extracts go, however, it may be advisable to stick with ingredients standardized to native constituents, are absorbed into the body, and are backed by clinical research.

EphB2 mutation linked with prostate cancer risk in african-americans

Wed, 21 Sep 2005 19:09:38 PST

( from http://www.rxpgnews.com ) Researchers have identified a gene mutation that may increase the risk of prostate cancer up to three times in African-American men with a family history of the disease.

The study, by scientists at 13 research centers, found that mutations in a gene known as EphB2 occurred in 15 percent of African-American men with a strong family history of prostate cancer. The mutation was found in only 5 percent of African-American men with no family or personal history of the disease and in less than 2 percent of European-American men with no history of the disease.

Prostate cancer rates are extremely high in African-American men. Until now, no gene mutations have been identified that contribute to hereditary prostate cancer and prostate-cancer susceptibility specifically in African-American men.

Next, we must learn more about how this mutation contributes to cancer, and we must screen for the mutation in a much larger group of African-American men with prostate cancer to verify its association with the disease.

Then, says Kittles, a specialist in prostate-cancer genetics in African Americans, perhaps we can begin using this mutation to help estimate prostate-cancer risk in African-American men.

The findings are the first to come out of the African-American Hereditary Prostate Cancer (AAHPC) study network, a group of 112 African-American families nationally who have volunteered to help in research to identify genetic risk factors for prostate cancer. Families in the network have had four or more cases of prostate cancer in the family.

This as an exciting extension to our original findings implicating EphB2 as a prostate-cancer tumor-suppressor gene, says principal investigator John D. Carpten, of the Translational Genomics Research Institute.

These data now suggest that mutations in this gene might predispose African-American men to prostate cancer in a significant way.

Other evidence suggesting that EphB2 could be a prostate-cancer susceptibility gene include its location on chromosome 1. After sequencing the gene from each volunteer, the investigators found that 11 of the 72 men (15.3 percent) had a mutation designated K1019X. The same mutation was found in only 5.2 percent in a control group of 329 healthy African-American men and in only 1.7 percent of 231 European-American control samples.

The findings indicate that the K1019X mutation is found mainly in African-American men, that it is particularly prevalent in African-American men with a family history of prostate cancer, and that it increases the risk of prostate cancer in these men almost three-fold.

Given its high frequency in hereditary cases, we believe that this mutation is probably associated with hereditary prostate cancer in African-American men, Kittles says.

Committee Supports New Indication for EGFR Inhibitor Erlotinib

Wed, 14 Sep 2005 21:31:38 PST

( from http://www.rxpgnews.com ) OSI Pharmaceuticals, Inc. (Nasdaq: OSIP) and Genentech, Inc. (NYSE: DNA) announced today that the Oncologic Drug Advisory Committee (ODAC) appointed by the U.S. Food and Drug Administration (FDA) voted 10 to 3 in favor of recommending approval of Tarceva® (erlotinib) in combination with gemcitabine for the treatment of advanced pancreatic cancer in patients who have not received previous chemotherapy. Tarceva is the first drug in a Phase III trial to have shown a significant improvement in overall survival when added to gemcitabine chemotherapy in first-line pancreatic cancer. Tarceva is an oral tablet currently approved for use in non-small cell lung cancer (NSCLC) for patients whose disease has progressed after one or more courses of chemotherapy. The FDA will now review the ODAC recommendation and a decision on Tarceva approval is anticipated by November 2, 2005.

"We are pleased with the recommendation of the advisory committee and we look forward to the FDAs decision on our pancreatic cancer application," said Colin Goddard, Ph.D., Chief Executive Officer of OSI Pharmaceuticals. "Tarceva is the first new potential therapy in nine years to have shown, in a randomized clinical trial, a statistically significant improvement in survival of patients suffering from advanced pancreatic cancer, a disease with a very poor prognosis for most patients."

Pancreatic cancer has the highest one-year mortality rate of any cancer. The average life expectancy for a patient diagnosed with metastatic pancreatic cancer is three to six months, according to The Pancreatic Cancer Action Network (PanCAN), a national patient advocacy organization for the pancreatic cancer community.

"We are encouraged by the ODACs recommendation as Tarceva represents a new advance in the struggle against pancreatic cancer. There is a tremendous need for new treatment options for this difficult-to-treat cancer," stated Hal Barron, M.D., Genentechs senior vice president, development and chief medical officer.

The randomized Phase III clinical study of Tarceva, in combination with gemcitabine chemotherapy, met its primary endpoint of improving survival. This international study was a multi-center, double-blind, placebo-controlled Phase III trial evaluating Tarceva in patients with unresectable locally advanced or metastatic pancreatic cancer. The study randomized 569 patients to receive gemcitabine plus concurrent Tarceva or gemcitabine plus placebo; 521 patients were randomized to receive 100 mg/day of Tarceva or placebo, and 48 patients were randomized to receive 150 mg/day of Tarceva or placebo. The ODAC review focused on the 100 mg/day cohort.

Compared to gemcitabine plus placebo, those patients receiving gemcitabine plus Tarceva 100 mg/day demonstrated a statistically significant (23 percent) improvement in overall survival (hazard ratio = 0.81, p = 0.028), which can also be referred to as a 19 percent reduction in the risk of death. After one year, 23 percent of patients receiving Tarceva plus gemcitabine were alive compared to 17 percent of patients receiving gemcitabine plus placebo. A statistically significant improvement in progression-free survival (hazard ratio = 0.77; p = 0.006) was also demonstrated. Although no difference in tumor response was observed (8.6 percent in patients receiving Tarceva plus gemcitabine versus 7.9 percent in the gemcitabine plus placebo arm), the disease control rate (complete response + partial response + stable disease) was significantly improved (59 percent in patients receiving Tarceva plus gemcitabine versus 49 percent in the gemcitabine plus placebo arm, p = 0.036). Rash and diarrhea were the principal Tarceva-related side effects seen in the study and were generally characterized as mild-to-moderate.

Safety findings were generally consistent with previous studies of Tarceva in both monotherapy and combination settings. Rash was reported in 69 percent of patients who received Tarceva plus gemcitabine and in 30 percent of patients who received gemcitabine plus placebo. Diarrhea was reported in 48 percent of patients who received Tarceva plus gemcitabine and in 36 percent of patients who received gemcitabine plus placebo. Two percent of the patients discontinued Tarceva because of rash and two percent because of diarrhea. Possible interstitial lung disease (ILD) was experienced in 2.3 percent of patients in the Tarceva plus gemcitabine arm compared with 0.4 percent in the gemcitabine plus placebo arm. The incidence of serious ILD-like events in the Tarceva and gemcitabine arm was higher than the 0.8 percent incidence reported for both the Tarceva monotherapy and placebo arms in the Tarceva pivotal study in advanced NSCLC. The incidence of possible ILD from all clinical studies with Tarceva is 0.7 percent.

According to the World Health Organization more than 216,000 people worldwide are diagnosed each year with pancreatic cancer. The American Cancer Society predicts that in 2005 about 32,180 people in the United States will be diagnosed with pancreatic cancer and about 31,800 will die of the disease. Although pancreatic cancer accounts for 2 percent of new cancer cases in the United States, it is the fourth leading cause of all cancer deaths. Most pancreatic tumors originate in the exocrine duct cells or in the cells that produce digestive enzymes (acinar cells). Called adenocarcinomas, these tumors account for nearly 95 percent of pancreatic cancers.

Tarceva is an oral tablet currently approved for use in non-small cell lung cancer (NSCLC) for those patients whose disease has progressed after one or more courses of chemotherapy. Tarceva is a small molecule designed to target the human epidermal growth factor receptor 1 (HER1) pathway, which is one of the factors critical to cell growth in a number of different cancer types. HER1, also known as EGFR, is a component of the HER signaling pathway, which plays a role in the formation and growth of numerous cancers. Tarceva is designed to inhibit the tyrosine kinase activity of the HER1 signaling pathway inside the cell, which may block tumor cell growth. Tarceva is the only EGFR therapy to show in a Phase III trial improved survival for advanced NSCLC patients. Additional early-stage trials of Tarceva are being conducted in other solid tumors. For Tarceva full prescribing information, please call 1-877-TARCEVA or visit http://www.tarceva.com.

OSI Pharmaceuticals is committed to "shaping medicines and changing lives" by discovering, developing and commercializing high-quality and novel pharmaceutical products that extend life or improve the quality of life for cancer and diabetes patients worldwide. The company operates through two business teams, (OSI) Oncology and (OSI) Prosidion. (OSI) Oncology is focused on developing molecular targeted therapies designed to change the paradigm of cancer care. (OSI) Prosidion is committed to the generation of novel, targeted therapies for the treatment of type 2 diabetes and obesity. OSIs flagship product, Tarceva® (erlotinib), is the first drug discovered and developed by OSI to obtain FDA approval and the only EGFR inhibitor to have demonstrated the ability to improve survival in both non-small cell lung cancer and pancreatic cancer patients. OSI markets Tarceva through partnerships with Genentech, Inc. in the U.S. and with Roche throughout the rest of the world. For additional information about OSI, please visit http://www.osip.com.

In addition to Tarceva, (OSI) Oncology exclusively markets Novantrone® (mitoxantrone concentrate for injection) for its approved oncology indications and markets Gelclair® Bioadherent Oral Gel for the relief of pain associated with oral mucositis. The research and development pipeline consists of novel molecularly targeted anti-cancer agents focused on signal transduction pathways involved in cell proliferation, apoptosis and angiogenesis. The most advanced of these programs, targeting the co-inhibition of c-kit and VEGFR, has two candidates in development.

Genentech is committed to changing the way cancer is treated by establishing a broad oncology portfolio of innovative, targeted therapies with the goal of improving patients' lives. The company is the leading provider of anti-tumor therapeutics in the United States. Genentech is leading clinical development programs for Rituxan® (Rituximab), Herceptin® (Trastuzumab), Avastin® (bevacizumab) and Tarceva® (erlotinib), and markets all four products in the United States alone (Avastin and Herceptin), with Biogen Idec Inc. (Rituxan) or with OSI Pharmaceuticals (Tarceva). Genentech has licensed Rituxan, Herceptin, and Avastin, and OSI Pharmaceuticals has licensed Tarceva to Roche for sale by the Roche Group outside of the United States.

The company has a robust pipeline of potential oncology therapies with a focus on four key areas: angiogenesis, apoptosis (i.e. programmed cell death), the HER pathway and B-cell biology. Potential oncology therapies directed at the HER pathway include a therapeutic antibody currently in Phase II trials. Also in early development are a small molecule directed at the hedgehog pathway, a soluble human protein targeting apoptosis and a humanized anti-CD20 antibody for hematology/oncology indications.

PSA remains the best indicator of cancer recurrence after surgery

Tue, 13 Sep 2005 04:31:38 PST

( from http://www.rxpgnews.com ) Despite recent claims by some urologists that measuring the blood protein prostate-specific antigen (PSA) may not be effective in predicting risk of prostate cancer, a Johns Hopkins study of more than 2,000 men confirms that PSA remains the best measure of the likelihood of cancer recurrence after surgery.

Results of the study, published in the October issue of The Journal of Urology, demonstrated that men with high PSA levels prior to prostate removal surgery were significantly more likely to have advanced clinical stages of cancer, evidence of higher grade cancers in surgically removed tissue, and spread of cancer cells beyond the prostate. In addition, increasing PSA was significantly associated with increased risk of cancer recurrence after surgery, even in men with lower PSA levels prior to surgery.

The study was led by Stephen J. Freedland, M.D., clinical instructor of urology, and Alan W. Partin, M.D., Ph.D., professor and chair of urology at Johns Hopkins' Brady Urological Institute.

"In our study, PSA levels measured before prostate removal surgery were significantly associated with the risk of recurrent cancer after surgery," Freedland says. "These data support the notion that PSA remains the best available prostate cancer tumor marker. It certainly suggests that the PSA era is alive and well."

PSA is a protein produced by cells of the prostate gland. Prostate cancer can increase PSA, so the higher the PSA level, the greater the likelihood that a patient has prostate cancer. Also, higher PSA values generally reflect larger, more aggressive cancers. Freedland acknowledges that because PSA provides physicians with a measure of a patient's prostate health at a single point in time, it's "far from perfect." However, he says, "it's better than anything else we have."

"As a screening tool, PSA has done what we wanted it to do," Freedland says. "It detects advanced disease early and reduces the likelihood of metastatic disease."

For the study, Freedland and colleagues reviewed patient records for 2,312 men who had prostate removal surgery at Johns Hopkins between 1992 and 2004. All operations were performed by Patrick C. Walsh, M.D., professor and former chair of urology. The research team compared the association between preoperative PSA and the risk of cancer recurrence after surgery.

During an average follow-up of five years, 211 men (10 percent) had signs of recurrent cancer. Higher PSA levels prior to surgery were significantly associated with increased risk of cancer after surgery. Compared to men with PSA levels less than 10 nanograms per milliliter, men with PSA values between 10 and 19.9 nanograms per milliliter were more than three times more likely to develop cancer after surgery. Men with PSA levels of 20 nanograms per milliliter or greater were more than five times more likely to develop cancer after surgery than those with low PSA levels.

Even in men with PSA values of less than 10 nanograms per milliliter, increasing PSA was significantly associated with increased risk of cancer after surgery. For each two-point increase in PSA, the risk of cancer after surgery approximately doubled.

"From our study and others, it is clear that a single PSA value is an extremely useful measure of a patient's risk of progression after surgery," Freedland says. "However, looking at how quickly the PSA increases over time is likely to be even more informative than a single value.

Expensive robot-assisted prostate surgery has possible benefits

Mon, 29 Aug 2005 22:30:38 PST

( from http://www.rxpgnews.com ) Although minimally invasive prostate removal aided by a robot can lead to less blood loss, shorter hospital stays and fewer complications, there is no evidence that the procedure improves cure rates, according to a new technology assessment.

In addition, robotic surgery, in high demand among patients, can lose money for hospitals because of its expense and special training required, according to the new review of studies by ECRI.

ECRI is a nonprofit health services research agency that produces systematic evidence reviews on medical devices, drugs, biotechnologies, procedures and behavioral health services.

The review of 625 cases looks at two studies that compared the three procedures available to patients: traditional open surgery, laparoscopic (also known as minimally invasive) surgery and robotic-assisted laparoscopic surgery.

In the review, average blood loss was significantly lower for patients who underwent either of the two minimally invasive procedures: less than 150 ml for robotic-assisted and 382 ml for non-robotic, while the average blood loss for open radical surgery in the two studies was 418 ml and 910 ml.

Cancer cure rate, measured by presence of cancerous cells at the surface of the removed prostate, and by PSA levels following surgery, was nearly identical for all three procedures.

Hospital stay was significantly shorter with robotic-assisted prostatectomy compared to open surgery in both studies, 25.9 hours versus 52.8 hours in one study.

One study reported significant difference in catheterization time: 7 days for robotic-assisted patients, 7.9 days for non-robotic laparoscopy patients and 15.8 days for open surgery patients.

Open prostatectomy had a significantly higher overall complication rate of 15 percent, while non-robotic laparoscopic prostatectomy had a rate of 10 percent and robotic-assisted had a complication rate of 5 percent.

Prostate cancer patients' biggest concerns -- after cure -- are the possible side effects of surgery, including urinary incontinence and sexual impotency. Data on these side effects from robotically assisted prostatectomy were sketchy at best, and no evidence was available to indicate that any surgical method emerged as better than another for these side effects.

So far, patient demand, not evidence, is the driving force behind the rise in robotic-assisted prostatectomy, according to report co-author Diane Robertson, director of Health Technology Assessment Services for ECRI.

Robertson says that the concept of minimally invasive surgery is highly attractive to patients, with many willing to travel for the robotic procedure, but she cautions that patients should choose based on surgeon experience and evidence on efficacy rather than just picking the latest technology.

"If you have to choose between someone who hasn't performed many robotic surgeries and a person who has performed many open procedures -- take the open procedure," says Peter G. Schulam, M.D., Ph.D., a urology professor at the David Geffen School of Medicine at UCLA.

Schulam routinely performs non-robotic laparoscopy, the more technically difficult of the minimally invasive surgeries.

Michael Esposito, M.D., a surgeon in Hackensack, N.J., who has performed about 425 robot-assisted surgeries, explains, "Robotics is a modification tool that further refines laparoscopy." Esposito says that robotics offers a three-dimensional view with much greater clarity, made possible with a binocular telescope held by one of the robotic arms.

Robotics allows surgeons to work seated at a console a few feet away from the operating table, pushing a joystick and pressing foot controls to remotely manipulate the three robotic arms at the bedside.

One arm positions a high-resolution camera, while the other two arms control the surgical instruments. "Robotic [hands] are wristed instrument that can open, close, flex and rotate 170 degrees," Esposito says. "They're so small and meticulous that you can scale movements and do extremely fine work."

Robotics is meant to eliminate hand tremors, but some surgeons find the lack of contact with instruments disconcerting. Esposito says that, once experienced with robotics, "your vision becomes a surrogate for tactile feedback."

Schulam says that both forms of minimally invasive surgery lead to shorter recovery and less pain "because there's no stretching of muscle, and possibly, less blood loss." Also, "patients prefer the five smaller holes over a larger midline incision."

Cost was the one area in which the older open surgery was the clear winner: Open radical prostatectomy costs $487 less a case than non-robotic laparoscopy and $1,726 less than robot-assisted prostatectomy.

According to the review, "Shorter operative time and decreased hospital stays associated with the robotic procedure did not make up for the cost of the additional equipment expenditure." Estimated costs of the robotic system to a provider run about $1.2 million a year, with maintenance costs of $120,000 a year and one-time costs of $1,500 a case.

"Hospitals have to consider whether they can use the system for more than one type of procedure to make it worth the capital equipment investment, if the institute can use it for many applications," says Robertson. She adds that many operating rooms are not big enough to accommodate the robotic system.

Predicting prostate cancer outcome with activated Stat5 protein

Mon, 15 Aug 2005 17:46:38 PST

( from http://www.rxpgnews.com ) Researchers from Lombardi Comprehensive Cancer Center at Georgetown University found that testing for an activated Stat5 protein in prostate tumor tissue effectively predicts which men have a form of prostate cancer that may become more aggressive and life threatening.

In the August 15 issue of Clinical Cancer Research, the researchers report that "Stat5" protein in the nucleus of prostate cancer cells was a significant predictor of which patients would develop a worrisome recurrence years after their prostate cancer was initially treated. Stat5 is a protein that, when activated, signals cancer cells to continually grow and survive. The study investigated prostate cancer biopsies or prostate cancer tissues obtained from surgery from 357 prostate cancer patients, and matched active Stat5 levels with outcome.

Given further validation, the findings offer hope that a "biomarker" can be developed to help oncologists and urologists to identify patients that are more likely to have a recurring and/or eventually life-threatening prostate cancer. Specifically, these patients with potentially aggressive prostate cancer should be actively treated and closely monitored in contrast to men with less aggressive prostate cancer who may safely choose "watchful waiting," especially if they are elderly, the researchers say.

Sorting out the few aggressive prostate tumors from the many that are indolent is a problem that has plagued the treatment of prostate cancer, said Marja Nevalainen, M.D., Ph.D., assistant professor in the Department of Oncology at Lombardi Comprehensive Cancer Center and principal investigator of the study.

"Most patients diagnosed with prostate cancer have slow-growing tumors that don't need aggressive therapy, but doctors do not have a way to identify the few men whose cancer is potentially dangerous. The result is that many patients are over-treated," she said.

"If future studies with Stat5 continue to show that it can help in predicting disease outcome, then we can test tumor biopsy samples for Stat5 and tailor treatment accordingly," Nevalainen said.

In the study, Georgetown researchers found that patients with "mid-grade" tumors who had high levels of activated Stat5 in their prostate cancer cells were 1.7 times more likely to experience disease progression compared to patients without activated Stat5. That corresponds to a 15-year, progression-free survival of 46 percent versus 62 percent, respectively.

"Mid-grade tumors are the most difficult to predict for the clinical outcome, said Nevalainen, "therefore, the most immediate use of Stat5 in prostate cancer as a marker would be for identification of the subgroup of mid-grade prostate cancers that are likely to progress early to androgen-independence and metastatic disease" said Nevalainen. "We feel that patients in this group who test positive for activated Stat5 should not remain treated with watchful waiting only, but should be actively and extensively treated."

When biopsy samples from all the patients in the study were analyzed and Stat5 readings were compared to their outcome, those with activated Stat5 had a progression-free survival rate of 44 percent, compared to 65 percent in patients whose cancer was free of activated Stat5.

These findings are the latest in a series of studies led by Nevalainen highlighting the role of Stat5 in prostate cancer development.

Among Nevalainen's earlier findings:

* Stat5 protein is particularly plentiful in the most aggressive prostate cancers, which have often spread by the time they are diagnosed.
* Stat5 can be experimentally inhibited - active Stat5 protein can be stopped before it reaches the DNA of the cell and triggers growth. This research has led to work to develop a pharmacological agent for human use. "There are only few treatment options available for advanced prostate cancer now, and we hope that we can develop a drug that might offer hope for patients with aggressive prostate cancer in the future," she said.

PSA velocity shown to be associated with tumor stage

Fri, 29 Jul 2005 00:46:38 PST

( from http://www.rxpgnews.com ) Men who have a higher rate of increase in their PSA value in the year prior to their prostate cancer diagnosis have a significantly higher risk of death following radiation therapy, according to a study in this issue of JAMA.

Information obtained from serial PSA values in the form of a PSA velocity (i.e., the change in PSA level during the year prior to diagnosis) has been shown to be significantly associated with tumor stage, grade, time to prostate cancer-specific death following radical prostatectomy, according to background information in the article.

Anthony V. D'Amico, M.D., Ph.D., of Brigham and Women's Hospital and the Dana Farber Cancer Institute, Boston, and colleagues evaluated whether a PSA velocity greater than 2.0 ng/mL during the year prior to diagnosis was significantly associated with prostate cancer-specific death following radiation therapy (RT). The study, conducted between January 1989 and December 2002, included 358 men treated with RT for localized prostate cancer. One-hundred twenty-five men were classified as having low-risk prostate cancer (clinical tumor category T1c or T2a and PSA level less than 10.0 ng/mL and Gleason score 6 or less; 233 men had higher-risk disease, stratified by the PSA velocity.

The researchers found that a PSA velocity greater than 2.0 ng/mL per year was significantly associated (12 times increased risk) with a shorter time to prostate cancer-specific death and all-cause death (2.1 times the risk) when compared with men whose PSA velocity was 2.0 ng/mL per year or less. Men presenting with low-risk disease and a PSA velocity greater than 2.0 ng/mL per year had a 7-year estimate of prostate cancer-specific death rate of 19 percent compared with 0 percent for men whose PSA velocity was 2.0 ng/mL per year or less. The corresponding values for men with higher-risk disease were 24 percent and 4 percent, respectively.

"Such men [higher PSA velocity] who are planning to undergo RT and are in good health could be considered for RT combined with androgen suppression therapy because this approach improves survival in men with higher-risk disease," the authors conclude.

Predicting risk of death after radical prostatectomy

Thu, 28 Jul 2005 23:16:38 PST

( from http://www.rxpgnews.com ) Clinical factors including the time to biochemical recurrence following surgery can help predict the risk of prostate cancer death for patients following a radical prostatectomy, according to a study in the July 27 issue of JAMA.

Radical prostatectomy (removal of the prostate) is one of the most common treatments for prostate cancer and generally provides excellent cancer control, according to background information in the article. However, approximately 35 percent of patients will develop a prostate-specific antigen (PSA) recurrence ("biochemical recurrence") within 10 years after surgery. Due to the sensitivity of PSA to detect disease recurrence early, many patients have a long interval between biochemical recurrence and the development of local recurrence or distant metastasis.

Given the protracted natural history, the researchers had previously identified clinical variables to help stratify patients for risk of metastasis: time from surgery to biochemical recurrence, pathological Gleason score (a grading system for prostate tumors), and PSA doubling time (PSADT; the time it takes for the PSA value to double). Previous research has confirmed that a short PDADT is a risk factor for clinical progression and prostate cancer-specific death.

Stephen J. Freedland, M.D., of The Brady Urological Institute, Johns Hopkins Medicine, Baltimore, and colleagues conducted a study to 1) identify clinical factors that are associated with increased risk for prostate cancer-specific death following radical prostatectomy, and 2) to identify men who are at high risk and may benefit from aggressive treatment and as well as to identify those men who are at low risk and can be safely observed. The study included 379 men who had undergone radical prostatectomy between 1982 and 2000 and who had a biochemical recurrence. The average follow-up after surgery was 10.3 years.

The researchers found that PSA doubling time (less than 3.0 vs. 3.0-8.9 vs. 9.0-14.9 vs. 15.0 or more months), pathological Gleason score (7 or less vs. 8-10), and time from surgery to biochemical recurrence (3 or less vs. greater than 3 years) were all significant risk factors for time to prostate-specific death. Using these 3 variables, tables were constructed to estimate the risk of prostate cancer-specific survival at year 15 after biochemical recurrence.

Patients with a PSADT less than 3 months had a median survival of 6 years. Patients with a PSADT less than 3 months, biochemical recurrence 3 years or less after surgery, and a pathological Gleason score of 8-10 had a median survival of 3 years. Patients with a PSADT of 15 or more months and a biochemical recurrence more than 3 years after surgery had a 100 percent prostate cancer-specific survival.

"Using the current data, patients at high risk of death due to prostate cancer can be identified. These patients should be offered aggressive combined multimodality treatment using hormonal and cytotoxic chemotherapy, particularly in light of recent data suggesting that chemotherapy can modestly, but significantly, prolong survival in patients with hormone refractory disease," the authors write.

Normal life after radiation for prostate cancer

Fri, 15 Jul 2005 23:59:38 PST

( from http://www.rxpgnews.com ) Men receiving radiation therapy to combat early-stage prostate cancer are still able to achieve an erection and face a low rate of incontinence one year following treatment, according to a new study published in the July 15, 2005 issue of the International Journal of Radiation Oncology*Biology*Physics, the official journal of ASTRO, the American Society for Therapeutic Radiology and Oncology.

Researchers enrolled 98 men from 24 institutions and set out to gauge the health-related quality of life in patients receiving low-dose rate prostate brachytherapy, a form of internal radiation therapy in which tiny radioactive seeds are implanted directly into the prostate gland to battle the cancer.

Patients were given three separate health-related quality of life questionnaires a total of five times before, during and after undergoing radiation therapy to allow researchers to evaluate what effect their treatment was having on them. The two most important side effects studied were sexual and urinary function.

The study reports that one year after receiving treatment, 78 percent of the men were able to achieve an erection, both with and without assistance. However, nearly 50 percent of the men did experience some loss of sexual function, such as reduced desire, activity and satisfaction as well as fatigue.

Although the overall rate of incontinence was low at 1 percent, some men did have difficulty urinating at the one-year mark. Typically, incontinence increases at the beginning of treatment and is completely gone one year after treatment.

"This is the first multi-institutional study of its kind," said Steven J. Feigenberg, M.D., lead author of the study and a radiation oncologist at Fox Chance Cancer Center in Philadelphia. "This study has provided us with valuable data that will help radiation oncologists better address possible side effects patients may have after receiving seed implants for prostate cancer."

Continuum of prostate cancer risk at all values of PSA - Study

Fri, 08 Jul 2005 13:28:38 PST

( from http://www.rxpgnews.com ) A new study indicates there is no specific PSA value that has both high sensitivity and high specificity for monitoring healthy men for prostate cancer, but rather there is a continuum of prostate cancer risk at all values of PSA, according to a study in the July 6 issue of JAMA.

One of the most common cancer screening activities in the United States is the measurement of prostate-specific antigen (PSA) levels for the early detection of prostate cancer, according to background information in the article. In 2001, approximately 75 percent of men in the United States aged 50 years and older reported that they had previously undergone PSA screening and 54 percent have reported regular PSA screening. In general, prostate biopsy has not been recommended unless PSA levels exceed a threshold value, generally 4.0 ng/mL, with slightly lower values recommended recently by some researchers. Prostate cancer screening with PSA has been controversial, as no studies have proven that this strategy reduces death from prostate cancer.

Ian M. Thompson, M.D., of the University of Texas Health Science Center at San Antonio, and colleagues conducted a study to determine the effectiveness of PSA testing by estimating the receiver operating characteristic (ROC) curve (a measure of diagnostic accuracy) for PSA. The researchers analyzed data from the Prostate Cancer Prevention Trial, a randomized, prospective study conducted from 1993 to 2003 at 221 U.S. centers. Participants were 18,882 healthy men aged 55 years or older without prostate cancer and with PSA levels less than or equal to 3.0 ng/mL and normal digital rectal examination results, followed up for 7 years with annual PSA measurement and digital rectal examination. If PSA level exceeded 4.0 ng/mL or rectal examination result was abnormal, a prostate biopsy was recommended. After 7 years of study participation, an end-of-study prostate biopsy was recommended in all cancer-free men.

For this analysis, the authors included 8,575 men in the placebo group of the trial who had at least 1 PSA measurement and digital rectal exam in the same year. Of these men, 5,587 (65.2 percent) had at least 1 biopsy, and of these, 1,225 (21.9 percent) were diagnosed with prostate cancer.

The researchers found that for detecting any prostate cancer, PSA cutoff values of 1.1, 2.1, 3.1, and 4.1 ng/mL yielded sensitivities of 83.4 percent, 52.6 percent, 32.2 percent, and 20.5 percent, and specificities of 38.9 percent, 72.5 percent, 86.7 percent, and 93.8 percent, respectively.

"... a clear-cut decision rule for prostate biopsy based on PSA values would be challenging to derive from these data. On one hand, the commonly used cutoff value of 4.1 ng/mL would have a 6.2 percent false-positive rate (1-specificity) but would detect only 20.5 percent of cancer cases (sensitivity). To improve cancer detection, the cutoff could be lowered to 1.1 ng/mL, thus detecting 83.4 percent of cancer cases, but would subject 61.1 percent of men without cancer to prostate biopsy. The recently recommended cutoff of 2.6 ng/mL would detect only 40.5 percent of cancer cases. ...there is no single cutoff that would simultaneously yield both high sensitivity and high specificity," the authors write.

"The delay in diagnosis of high-grade tumors until PSA levels exceed current threshold 'normal' values could also explain why there is a 35 percent risk of subsequent treatment after radical prostatectomy, presumably due to disease recurrence. However, lowering the threshold would have 2 consequences: increased biopsy rates and the possibility of increased detection and treatment of biologically inconsequential cancers. Currently, men in the United States have a 17.3 percent lifetime risk of prostate cancer diagnosis, while the lifetime risk of prostate cancer death is 3 percent," the researchers write.

"The implications of this analysis are substantial. Prior to clinical use of biomarkers or other tests for cancer screening, properly designed validation studies are essential. A multi-step process for validation is currently used by the Early Detection Research Network of the National Cancer Institute. While prostate cancer is not unique, it has a variable natural history, ranging from markedly aggressive to indolent. Consideration should be given to the development of biomarkers that incorporate disease prognosis. Finally, it will be a challenge to the medical community to change the long-held notion that there is a 'normal' PSA level. Patients and health care professionals must be re-educated that there is a continuum of risk and no clearly defined PSA cutpoint at which to recommend biopsy. It will be the patient, in concert with his health care professional, who will ultimately have to weigh the sensitivity-specificity tradeoffs in combination with the uncertain natural history of the disease to determine whether further evaluation with a prostate biopsy is appropriate," the authors conclude.

Hyperthermia Therapy as a New Approach to Treat Prostate Cancer

Tue, 21 Jun 2005 21:40:38 PST

( from http://www.rxpgnews.com ) BSD Medical Corp. (AMEX:BSM) has announced the conclusion of a highly successful conference of the 2005 annual European Society of Hyperthermic Oncology (ESHO) held in Graz, Austria, in which major breakthroughs in therapies tied to BSD's cancer treatment equipment were reported. Of the 74 presentations made at the conference, some of the highlights are being reported in several follow-up press releases.

Dr. Sergio Maluta of the Department of Radiology at the University Hospital in Verona, Italy reported the results of a 119-patient clinical study involving locally-advanced prostate cancer (stages T3-T4, which are spread beyond the prostate capsule) in which the BSD-2000 deep regional hyperthermia system was used in combination with radiation therapy to minimize side effects.

Side effects from radiating the prostate are a serious concern because of radiation exposure of the rectum, bladder and other organs. The study used hyperthermia therapy to increase the effectiveness of radiation without increasing the toxicity of the combined treatments.

Of the 119 men treated from 1998 through 2004, 15 were lost at follow-up, but of the remaining 104 patients followed, 99 were still alive and 96 were disease-free. Of the 104 patients tracked, 3 died because of other diseases and only 2 died because of the progression of their cancer. Overall 3-year actuarial survival was 95%, compared to a typical five-year overall survival rate of 60-73% using conventional radiation therapy alone. Precedents for this study were prior research performed at Mosk University, the University of Arizona, Duke University and Northwestern University.

Prostate-specific Membrane Antigen Emerging as an Important Therapeutic Target to Deal with Prostate Cancer

Tue, 21 Jun 2005 10:49:38 PST

( from http://www.rxpgnews.com ) Seattle Genetics, Inc. (Nasdaq:SGEN) and PSMA Development Company LLC (PDC), a joint venture between Progenics Pharmaceuticals, Inc. (Nasdaq:PGNX) and Cytogen Corporation (Nasdaq:CYTO), announced today that Seattle Genetics has licensed its proprietary antibody-drug conjugate (ADC) technology to PDC.

The license provides PDC with rights to utilize the ADC technology to link cell-killing drug payloads to PDC's fully human monoclonal antibodies that target prostate-specific membrane antigen (PSMA), which is highly expressed on both primary and metastatic prostate cancer cells.

"PSMA is emerging as an important therapeutic target because of its strong expression on prostate cancer and tumor vasculature and its limited presence on normal tissues, making it ideal for use as an ADC therapy," commented Clay B. Siegall, Ph.D., President and Chief Executive Officer of Seattle Genetics. "Our industry-leading ADC technology can link synthetic, cell-killing auristatin payloads to the PSMA-targeted antibodies developed by PDC, resulting in compounds that are designed to be more potent and effective in treating prostate cancer."

PSMA is a protein abundantly expressed on the surface of prostate cancer cells, with an increased expression in high-grade cancers, metastatic disease and hormone-refractory prostate cancer. PSMA is also present at high levels on the newly formed blood vessels, or neovasculature, needed for the growth and survival of many solid tumors. In contrast to other prostate-related antigens such as prostate-specific antigen (PSA), prostatic acid phosphatase (PAP) and prostate secretory protein, PSMA is a membrane glycoprotein that is not secreted. This unique expression pattern makes PSMA an excellent antigenic target for monoclonal antibody diagnostic and therapeutic options.

"We are encouraged by preclinical data demonstrating that PSMA can be effectively targeted by antibodies developed through PDC in combination with Seattle Genetics' ADC technology," said Michael D. Becker, Cytogen's President and Chief Executive Officer. "In addition to major ADC collaborations and licenses, Seattle Genetics has itself demonstrated the potential of this technology by advancing multiple ADC compounds into development. As we continue to advance PSMA programs through preclinical development and initiate clinical trials for our first fully human monoclonal antibody, we are building important clinical momentum which will set the stage for additional drugs coming from our unique PSMA technologies."

Under the terms of the multi-year agreement, PDC will pay Seattle Genetics a $2.0 million upfront fee for access to the technology for use with antibodies targeting the PSMA antigen. PDC has also agreed to make progress-dependent milestone payments and pay royalties on net sales of resulting ADC products. PDC is responsible for research, product development, manufacturing and commercialization of all products under the collaboration. Seattle Genetics will receive material supply and annual maintenance fees as well as research support payments for any assistance provided to PDC in developing ADC products.

About ADCs

ADCs utilize the targeting ability of monoclonal antibodies to deliver potent, cell-killing payloads to specific cells. Seattle Genetics has developed improved ADC technology employing synthetic, highly potent drugs that can be attached to antibodies through proprietary linker systems. The linkers are stable in the bloodstream and release the drug payload once inside target cells. ADCs can increase the therapeutic potential of the many antibodies with targeting ability but limited or no inherent cell-killing activity.

About Prostate Cancer

Prostate cancer is the most common type of cancer found in American men, other than skin cancer. The American Cancer Society estimates that there will be about 232,090 new cases of prostate cancer in the United States in the year 2005 and that about 30,350 men will die of this disease. Prostate cancer is the second leading cause of cancer death in men, exceeded only by lung cancer.

Delaying radiation for prostate cancer does not affect outcome

Tue, 14 Jun 2005 06:08:38 PST

( from http://www.rxpgnews.com ) For men diagnosed with prostate cancer, there is no risk of recurrence if external beam radiation therapy (EBRT) is delayed by several months. A study published in the July 15, 2005 issue of CANCER, a peer-reviewed journal of the American Cancer Society, finds delays of EBRT had no harmful impact on clinical outcome or biochemical marker levels in low-, intermediate- and high-risk patients.

Prostate cancer is generally a slow-developing malignancy that affects older men. However, treatment is still important for survival and includes surgery and radiation. The forms of available radiotherapy include external beam radiation 3D conformal radiation therapy (3DCRT), intensity modulated radiation therapy, or brachytherapy. Treatment delays of several months are quite common for men diagnosed with prostate cancer and can cause patients concern and anxiety.

While radiation treatment delays in other cancers are associated with increased mortality, little is known about the effect of delaying treatment on the outcome of prostate cancer. Stephen F. Andrews, D.O. and colleagues from the Fox Chase Cancer Center in Philadelphia reviewed the data from almost 1500 men treated for locally confined prostate cancer to investigate the effect of 3DCRT delay on outcome.

The investigators found that there was no difference in overall survival, disease specific survival, the incidence of distant metastases, and treatment failure for men who delayed 3DCRT more than nine months. Moreover, there was no difference in outcome for men with low-, intermediate-, and high-risk tumors who delayed treatment less than or more 3 months.

For men with locally confined prostate cancer, "patients and physicians can use this information to alleviate concerns and anxiety regarding delaying treatment in order to make a well-informed treatment decision," conclude the authors.

Groundbreaking discovery of the ETS-Related Gene (ERG)

Sun, 12 Jun 2005 06:07:38 PST

( from http://www.rxpgnews.com ) Researchers led by Dr. Shiv Srivastava from the Center for Prostate Disease Research (CPDR), Uniformed Services University of the Health Sciences (USU), report the groundbreaking discovery of the ETS-Related Gene (ERG) as one of the frequent proto-oncogene overexpressions in prostate cancer cells. This discovery provides a very promising addition to a select group of genes, whose expression is frequently altered in prostate cancer cells and could provide novel molecular targets for diagnosis, prognosis or therapy of prostate cancer in the future.

The report by Dr. Gyorgy Petrovics et al showing ERG expression alterations in a large fraction of prostate cancer cells is published in the latest issue (May 26, 2005) of leading cancer research journal Oncogene. Using laser capture microdissected prostate epithelial cells from malignant and benign prostate tissues and GeneChips, researchers identified ERG as the first proto-oncogene that is commonly overexpressed in early-phase prostate cancer.

The cancer-causing genes known as oncogenes and tumor suppressor genes have long been known to be major factors in the development of cancer cells, and mutation or altered expression of these genes has been identified in diverse human cancers. However, for prostate cancer, which is the most common non-skin cancer and the second leading cause of cancer-related deaths among men in the U.S., the identification of oncogenes and tumor suppressor genes that are altered in most prostate cancer cells have eluded scientists thus far.

Dr. Charles Bieberich, a leading prostate cancer researcher at the University of Maryland, Baltimore Campus, who is studying the regulation and function of a prostate tissue-specific tumor suppressor, the NKX3.1 homeobox gene, stated: "I find it very exciting that overexpression of a proto-oncogene transcription factor like ERG is associated with prostate cancer at such a high frequency." Dr. Beiberich's group also studies interactions of NKX3.1 with a prostate tissue-derived ETS factor (PDEF). "These novel observations warrant further studies looking into the functional effects of ERG overexpression in model systems of prostate cancer. It is likely that additional prostate cancer-relevant gene alterations also will be discovered by the microgenomics approach used in this study."

CPDR researchers went on to assess the cancer association of ERG change in combination with other prostate cancer marker genes. They found that when they combined ERG with two other genes, DD3 and AMACR, which are described by other laboratories as commonly overexpressed in prostate cancer, the three-gene panel exhibited cancer association in 98% of the prostate cancer patients tested. This result shows promise for prostate cancer diagnosis. Intriguing correlations of ERG overexpression features also have been noted for PSA recurrence-free survival of prostate cancer patients after radical prostatectomy.

Due to the previously established oncogenic functions of ERG, CPDR researchers also propose to explore ERG as a potential therapeutic target in prostate cancer treatment.

"This is a significant new finding, but it will take time to translate this into clinically useful products. The most likely first potential clinical application could be improved detection of prostate cancer by providing a novel and functionally relevant biomarker. However, the exploration of the therapeutic potential of ERG is equally important," said Dr. Robert Vessella from the University of Washington, Seattle, who is one of the pioneers in developing new diagnostic and prognostic cellular and molecular markers for prostate cancer. Dr. Vessella is one of the primary leaders of a research effort at the University of Washington that is defining mechanisms of prostate cancer metastasis.

Pros and Cons of All Possible Treatments of Prostate Cancer

Mon, 30 May 2005 21:17:38 PST

( from http://www.rxpgnews.com ) Prostate cancer continues to be a leading priority among medical researchers. For this reason, a special panel briefing dedicated to prostate cancer treatments and outcomes will be held during the 100th Annual Scientific Meeting of the American Urological Association (AUA) on May 25, 2005 in the Henry B. Gonzalez Convention Center in San Antonio. J. Brantley Thrasher, M.D., a spokesperson for the AUA and chair of urologic surgery at the University of Kansas Medical Center, will moderate the briefing, which will feature research on best treatments for high-grade prostate cancer.

Featured research includes:

Five-year Urinary and Sexual Outcomes After Radical Prostatectomy: Results from the Prostate Cancer Outcomes Study ( 672 ): Results have never been obtained of comprehensive, unbiased studies of outcomes following prostatectomy. Researchers followed prostatectomy patients for five years after their procedure to examine changes in urinary and sexual function. Problems with urinary control and sexual performance were found common up to five years after surgery, but functional outcomes were stable over the population.

A Cost and Revenue Analysis for Retropubic, Perineal and Robotic Prostatectomy at a Large Community Hospital ( 24 ): With the frequency of prostatectomies performed each year, it is important for hospital administrators to know which form of prostatectomy is most financially beneficial to their institution. Hospital records and financial data from 2003-2004 were analyzed to determine the cost and revenue for each type of prostate cancer treatment ( retropubic, perineal and laparoscopic-robotic assisted ). Cost was determined by factors such as length of stay, type of procedure and length of time to perform a procedure. Revenue was determined by cost and insurance type. Combining all those factors, retropubic prostatectomy was found to have the greatest cost advantage due to the lower hospital costs.

Variations Among High-Volume Surgeons in Rate of Complications After Radical Prostatectomy: Further Evidence that Technique Matters ( 188 ): Practice might make perfect for surgeons when it comes to performing prostatecomies. It has been shown that a strong correlation exists between surgeon, hospital volume and degree of success following prostatectomy, but the differences in outcomes among surgeons has not been measured. Surgical technique and post-op care among surgeons was evaluated to determine their importance in the outcomes following surgery. Surgeons that performed well in post-operative care, for example, tended to perform well in other areas confirming the theory that variations in technique and post-operative care play an important role in the outcome following the prostatectomy.

Technique of Radical Prostatectomy: A Head to Head Comparison of Retropubic, Perineal and Laparoscopic Access -Data on Perioperative Morbidity ( 684 ): Prostatectomies can be performed several ways, including perineal ( inserted through the perineum ), retropubic ( incision in the abdomen and reaching behind the pubic bone ) and laparscopic ( tube inserted in abdomen to perform minor surgeries ). Techniques were evaluated based on safety and efficacy, blood loss and operation time. Comparison found all three techniques effective in treating prostate cancer with very similar surgical margin rates.

Comparison of Radical Prostatectomy, Radiotherapy and Hormonal Therapy for Screen-Detected Prostate Cancer ( 1459 ): The purpose of screening for prostate cancer is to detect early warning signs so action can be taken against the disease when it reaches a certain level of seriousness. When detected early, patients have more flexibility in choosing treatment, weighing the effectiveness of a treatment against the detrements it brings to the quality of life. It is controversial as to what form of treatment is most preferred among patients, so researchers updated and evaluated results on prostate cancer patients who chose their own treatment and by doing so have stopped the progression of the disease. Radical prostatectomy was found to have the lowest progression rate following procedure with brachytherapy close behind.

Adjuvant Radiotherapy for Pathologic T3 Prostate Cancer: Results of a Randomized, Prospective Clinical Trial with Metastasis-Free Survival Endpoint ( 1665 ): Patients commonly use as an additional treatment following radical prostatectomy. The effect of radiotherapy combined with prostatectomy has never been measured to determine the rate of cancer-free survival. After close examination, radiotherapy was found to be effective in preventing relapses and normalizing PSA levels, but it did not have an effect on the growth of new cancers.

Radical Prostatectomy for Clinically Advanced Prostate Cancer in the PSA Era: 15-year Outcomes ( 826 ): Historically, patients with locally advanced prostate cancer have been told that they cannot undergo a prostatectomy for treatment. New research reports that this belief may be outdated. Eighty-percent of patients who underwent prostatectomies 15 years ago were reported as having remained cancer-free, proving that prostatectomies can be performed on patients with advanced prostate cancer. Not only did patients remain cancer-free for 15 years, but the prostatectomy did not cause adverse effects any worse than those experienced by prostatectomy patients with lesser grade cancer.

Quality of Life After Radical Prostatectomy or External Beam Radiotherapy for Localized Prostate Cancer ( 1017 ): External beam radiotherapy is the most common form of radiotherapy, where patients lie on their backs and X-rays are pointed at certain points of the body. This non-invasive treatment was compared to the surgical prostatectomy treatment to determine the quality of life following each. Both had similar results with prostatectomy patients experiencing lower quality of life only in the month immediately following surgery. Patients experienced declines in sexual function following both prcedures.

It is critically important to understand the pros and cons of all possible treatments of prostate cancer, said J. Brantley Thrasher, MD, who moderated the panel. This research presents a variety of findings for the many courses of action available.

QUADRAMET® with Docetaxel Demonstrate Good Palliative Effect in Prostate Cancer

Tue, 17 May 2005 09:06:38 PST

( from http://www.rxpgnews.com ) Cytogen Corporation (Nasdaq: CYTO - News), a product-driven biopharmaceutical company, today announced the publication of data from a phase II study of QUADRAMET® (samarium Sm-153 lexidronam injection), the Company's flagship product, in combination with docetaxel (Taxotere®, Aventis Pharmaceuticals, a member of the sanofi- aventis Group) for the treatment of patients with hormone refractory prostate cancer.

The published abstract is part of the proceedings at the 2005 American Society of Clinical Oncology (ASCO) Annual Meeting being held May 13- 17, 2005, at the Orange County Convention Center in Orlando, FL. The lead investigator was Anders Widmark, M.D., Ph.D., Professor, Department of Oncology, Umea University, Sweden.

"Two years ago at this meeting we published data from a pilot study showing the feasibility of combining taxane-based chemotherapy with QUADRAMET," said Dr. Widmark. "The additional data from this phase II study demonstrate good palliative effect lasting five months after the first treatment cycle in response to this combination therapy, which was well tolerated and simple to administer."

Study Details

The phase II study, known as the TAXSAM1 trial, was designed to evaluate the toxicity and efficacy of QUADRAMET in combination with docetaxel in 30 patients with progressive hormone refractory prostate cancer. Docetaxel was administered over a 30-minute infusion at a dose of 30 mg/m2. Eighteen to twenty-four hours prior to the fourth administration of docetaxel, the standard palliative dose of 1.0 mCi/kg of QUADRAMET was injected. Patients received a second cycle at PSA and/or clinical progression.

Results were reported for the first 20 patients in the study. Following the first cycle of therapy, grade 3 neutropenia was seen in two patients (at week two and four, respectively after QUADRAMET administration) and one patient had grade 4 neutropenia at week two after QUADRAMET. One patient had grade 2 thrombocytopenia four weeks after QUADRAMET. Upon progression, 14 patients received a second treatment cycle. The median interval between the beginning of the first and second treatment cycles was six months.

"Researchers at several leading cancer centers have recently initiated clinical studies to evaluate the combination of QUADRAMET and docetaxel for the treatment of patients with hormone refractory prostate cancer," said William Goeckeler, Ph.D., Senior Vice President of Operations at Cytogen. "These results from Dr. Widmark and his colleagues validate the growing interest in the role of QUADRAMET in combination with chemotherapy for the treatment of prostate and other tumors that have spread to bone."

About Prostate Cancer

According to the American Cancer Society, this year approximately 232,090 new cases of prostate cancer will be diagnosed in the United States and approximately 30,350 men will die of this disease. There is an unmet medical need for treating the disease, particularly for hormone refractory prostate cancer for which therapeutic options are limited.

About QUADRAMET

QUADRAMET is an oncology product that pairs the targeting ability of a small molecule, bone-seeking phosphonate (EDTMP) with the therapeutic potential of radiation (samarium Sm-153). Skeletal invasion by prostate, breast, multiple myeloma, and other cancers often creates an imbalance between the normal process of bone destruction and formation. QUADRAMET selectively targets such sites of imbalance, thereby delivering radioactivity to areas of the skeleton that have been invaded by metastatic tumor.

QUADRAMET has many characteristics which the Company believes are advantageous for the treatment of metastatic bone disease, including early onset of pain relief, predictable and reversible bone marrow toxicity or myelosuppression, ease of administration, and length of pain relief, lasting, on average, four months with a single injection. QUADRAMET is administered as an intravenous injection on an outpatient basis, and exhibits selective uptake in bone with little or no detectable accumulation in soft tissue.

Toremifene May Reduce Cancer Risk in Men with Precancerous Prostate Cells

Tue, 17 May 2005 01:53:38 PST

( from http://www.rxpgnews.com ) In a multicenter phase IIb study, the hormone drug toremifene (Acopodene) reduced the risk of prostate cancer development by nearly half in men with prostatic intraepithelial neoplasia (PIN), a precancerous condition that can progress to prostate cancer.

"This is the first time that a drug has shown promise for lowering the incidence of prostate cancer in men with PIN," said lead author David Price, MD, Director of Urologic Oncology and Clinical Research at Regional Urology, LLC in Shreveport, Louisiana. Toremifene, a hormonal therapy commonly used to treat women with advanced breast cancer, may work by blocking a particular estrogen receptor that has been implicated in prostate cancer development.
While PIN does not always lead to prostate cancer, prostate cancer usually develops in men with PIN. Approximately 10% of men who undergo prostate biopsies are diagnosed with PIN, and more than 30% of men with PIN will be diagnosed with prostate cancer within a year.

Currently, there is no effective treatment for PIN men with this condition receive periodic biopsies, and many live with a fear of developing cancer. Prostate cancer is the most common cancer in men in the United States more than 200,000 cases are expected to be diagnosed in 2005.

In this study, 514 men with PIN were randomly assigned to receive 20 mg, 40 mg, or 60 mg of toremifene or a placebo for one year, undergoing prostate biopsies at six and 12 months. The trial was completed in May 2004.

The cumulative incidence of prostate cancer was 31.2% in the placebo group at one year. Patients treated with 20 mg of toremifene for six months had a 22% reduction in prostate cancer, while patients who completed an entire year of treatment had a 48% reduction in prostate cancer risk (24.4% cumulative incidence). For the groups that received 40 mg and 60 mg of toremifene, the 12-month incidence of prostate cancer was also lower, but not statistically significant (18% and 25.3% risk reductions, respectively).

Toremifene was generally well tolerated, with the incidence of adverse events occurring at a similar rate in the toremifene-treated groups as the placebo group; the exception was fatigue, which occurred in 5% of patients treated with toremifene versus 3% of the placebo group.

"While these data are promising, more clinical trials are needed to determine whether toremifene should be widely prescribed to men with prostatic intraepithelial neoplasia," Dr. Price added.

New Advances in Prostate Cancer Treatment

Sun, 15 May 2005 02:22:38 PST

( from http://www.rxpgnews.com ) In a multicenter phase IIb study, the hormone drug toremifene (Acopodene) reduced the risk of prostate cancer development by nearly half in men with prostatic intraepithelial neoplasia (PIN), a precancerous condition that can progress to prostate cancer.

This is the first time that a drug has shown promise for lowering the incidence of prostate cancer in men with PIN, said lead author David Price, MD, Director of Urologic Oncology and Clinical Research at Regional Urology, LLC in Shreveport, Louisiana. Toremifene, a hormonal therapy commonly used to treat women with advanced breast cancer, may work by blocking a particular estrogen receptor that has been implicated in prostate cancer development.
While PIN does not always lead to prostate cancer, prostate cancer usually develops in men with PIN. Approximately 10% of men who undergo prostate biopsies are diagnosed with PIN, and more than 30% of men with PIN will be diagnosed with prostate cancer within a year. Currently, there is no effective treatment for PIN men with this condition receive periodic biopsies, and many live with a fear of developing cancer. Prostate cancer is the most common cancer in men in the United States more than 200,000 cases are expected to be diagnosed in 2005.

In this study, 514 men with PIN were randomly assigned to receive 20 mg, 40 mg, or 60 mg of toremifene or a placebo for one year, undergoing prostate biopsies at six and 12 months. The trial was completed in May 2004.

The cumulative incidence of prostate cancer was 31.2% in the placebo group at one year. Patients treated with 20 mg of toremifene for six months had a 22% reduction in prostate cancer, while patients who completed an entire year of treatment had a 48% reduction in prostate cancer risk (24.4% cumulative incidence). For the groups that received 40 mg and 60 mg of toremifene, the 12-month incidence of prostate cancer was also lower, but not statistically significant (18% and 25.3% risk reductions, respectively).

Toremifene was generally well tolerated, with the incidence of adverse events occurring at a similar rate in the toremifene-treated groups as the placebo group; the exception was fatigue, which occurred in 5% of patients treated with toremifene versus 3% of the placebo group.

While these data are promising, more clinical trials are needed to determine whether toremifene should be widely prescribed to men with prostatic intraepithelial neoplasia, Dr. Price added.

A Novel mTOR Inhibitor in Phase 2 as a Single Agent for Refractory Prostate cancer

Wed, 04 May 2005 22:14:38 PST

( from http://www.rxpgnews.com ) ARIAD Pharmaceuticals, Inc. (Nasdaq: ARIA) announced initiation of enrollment of patients with prostate cancer who have become refractory to standard hormone therapy in a multi-center Phase 2 clinical trial of its novel mTOR inhibitor, AP23573, as a single agent. Prostate cancer is the most common cancer diagnosis in men other than skin cancer. Progression to hormone-refractory disease is associated with a very poor prognosis, and current therapeutic options are severely limited.

This non-randomized study will evaluate the clinical benefit of AP23573 in well-characterized prostate cancer patients. Up to approximately 35 patients will be enrolled in the trial at several centers in the United States. AP23573 will be administered intravenously using a weekly dosing regimen. Patients will be followed for at least nine months after enrollment but may continue on AP23573 until disease progression occurs. Data on multiple mTOR-pathway biomarkers will be obtained to help identify patients who are most likely to benefit from treatment with AP23573.

"In addition to this new trial in prostate cancer, AP23573, which was designated as a fast-track product by the FDA for the treatment of sarcomas, is being studied in diverse solid tumors and hematologic malignancies," said Harvey J. Berger, M.D., chairman and chief executive officer at ARIAD. "Earlier this year, we established a series of drug-development goals, including launching this trial in a large potential clinical indication, and we are on track to achieve each of these key milestones."

About Prostate Cancer

It is estimated that more than 230,000 cases of prostate cancer will be diagnosed in the U.S. in 2005, and over 30,000 deaths will occur as a result of this disease. According to the American Cancer Society, one in six men will be diagnosed with prostate cancer during his lifetime. The exact cause of prostate cancer is unknown, although certain risk factors such as age, family history, race, diet and exercise have been linked to the disease. Overall, prostate cancer causes approximately 10 percent of all cancer-related deaths in men. Chemotherapy is the standard treatment for patients with hormone-refractory disease; however, its limitations are well documented in the literature as all patients eventually become resistant to chemotherapy over time.

About AP23573

The small-molecule drug, AP23573, starves cancer cells and shrinks tumors by inhibiting the critical cell-signaling protein, mTOR, which regulates the response of tumor cells to nutrients and growth factors, and controls tumor blood supply and angiogenesis through effects on Vascular Endothelial Growth Factor (VEGF) in tumor and endothelial cells. AP23573 also blocks the proliferation and migration of vascular smooth muscle cells, the primary cause of narrowing and reblockage of injured arteries, and is an analog of sirolimus, another mTOR inhibitor that has been approved for use in drug-eluting stents. AP23573 is currently in Phase 1 and 2 clinical trials in patients with solid tumors and hematologic cancers. AP23573 has been designated a fast-track product by the U.S. Food and Drug Administration for the treatment of soft tissue and bone sarcomas.

Satraplatin for its Use in Second-Line Treatment for Hormone Refractory Prostate Cancer Continues in Phase 3

Wed, 20 Apr 2005 09:29:38 PST

( from http://www.rxpgnews.com ) Spectrum Pharmaceuticals, Inc. (Nasdaq: SPPI) today announced that its co-development partner for satraplatin, GPC Biotech AG (Nasdaq: GPCB) (Frankfurt Stock Exchange: GPC), disclosed that the independent Data Monitoring Board (DMB) for the satraplatin Phase 3 SPARC registrational trial in second-line hormone refractory prostate cancer held a meeting on April 18, 2005 to review safety data from the ongoing study. The DMB reviewed the safety data from the first 262 patients who were randomized in the trial and had completed at least one cycle of treatment. After reviewing the data, the DMB reported that the design and conduct of the trial remain sound and recommended that the trial continue as planned.

As previously reported, GPC Biotech remains on schedule to complete patient enrollment in the SPARC trial by the end of 2005 and to complete the NDA (New Drug Application) filing with the U.S. FDA in the second half of 2006.

About Satraplatin

Satraplatin, an investigational drug, is a member of the platinum family of compounds. Over the past two decades, platinum-based drugs have become a critical part of modern chemotherapy treatments and are used to treat a wide
variety of cancers.

Worldwide sales of these drugs exceeded $2.2 billion in
2004. Unlike the platinum drugs currently on the market, all of which require intravenous administration, satraplatin is an orally bioavailable compound and is given as capsules that patients can take at home. An oral platinum drug could offer key advantages, including ease of administration and patient convenience, in a variety of applications.

Additionally, satraplatin is the only platinum-based compound to have shown efficacy in a randomized clinical
trial in prostate cancer. Prostate cancer is the most common cancer among men in the U.S. and Europe. The number of patients with this disease is expected to increase with the aging population. As the disease advances, patients are
often treated with hormone therapy. Once patients fail hormone therapy, becoming hormone-refractory, follow-on treatment involves a limited number of options, including chemotherapy.

For patients who then fail first-line chemotherapy, there are currently no approved second-line chemotherapy regimens. Satraplatin is in a Phase 3 registrational trial -- the SPARC trial -- as a second-line chemotherapy treatment for HRPC.

GPC Biotech has successfully completed a Special Protocol Assessment with the U.S. FDA and has
received a Scientific Advice letter from the European regulatory authority, the European Medicines Agency (EMEA). The FDA has also granted fast track designation to satraplatin for this indication.

Does Screening for Prostate Cancer with PSA Actually Save Men's Lives?

Sun, 10 Apr 2005 09:07:38 PST

( from http://www.rxpgnews.com ) Screening for prostate cancer with a PSA (prostate specific antigen) blood test, though routinely performed today in men middle-aged and older, remains a source of controversy. Questions continue about the test's overall effectiveness and its ability to actually save men's lives.

For example, elevated PSA levels don't necessarily equate with clinically significant prostate cancer. Some men faced with high test results, however, may have undergone unnecessary treatments, with debilitating side effects such as infertility, incontinence and impotence.

For others, a normal PSA has also be misleading. In these cases, undetected prostate cancer has grown and spread to other parts of the body, sometimes resulting in death.

Nevertheless, if caught early, men have a 100 percent, five-year survival rate - a surprisingly positive statistic compared to many other types of cancer. Clearly, early detection is a key to curing prostate cancer.

To put this controversy in perspective, a forum on "Controversies in the Screening and Early Detection of Prostate Cancer, will be held on Sunday, April 17, Room 204 Anaheim Convention Center at the 96th Annual Meeting of the American Association for Cancer Research.

The forum will feature two outspoken authorities in the field:

-- Otis W. Brawley, M.D., professor of Medicine, Hematology and Oncology at the Emory University School of Medicine and Professor of Epidemiology at the Emory Rollins School of Public Health, Atlanta, Ga.

-- Fritz H. Schroder, professor and chair of the Department of Urology, Erasmus University, Rotterdam, The Netherlands.

The session will be moderated by:

-- William G. Nelson V, M.D., Ph.D., professor in the departments of Oncology, Urology, Pharmacology and Molecular Sciences, Medicine, Pathology, and Radiation Oncology and Molecular Radiation Sciences, at Johns Hopkins University.

Members of the press are cordially invited to attend this session.

Advanced Prostate Cancer may be Curable

Sun, 03 Apr 2005 11:24:38 PST

( from http://www.rxpgnews.com ) New findings from Mayo Clinic indicate that cT3 prostate cancer, a disease in which the cancer has spread locally from inside the prostate to immediately outside it, is operable and has 15-year cancer survival rates of almost 80 percent.

"These patients have a better chance if they undergo surgery and are living longer than if they undergo radiation therapy," says Horst Zincke, M.D., Ph.D., Mayo Clinic urologist and senior study investigator.

Treatment of this type of prostate cancer has been controversial, as it is a stage 3 cancer in which the malignancy has spread. Due to its advanced stage, some physicians have considered it inoperable via radical prostatectomy, according to Dr. Zincke. He explains that many patients come to him for a second opinion after being told their cT3 prostate cancers could not be surgically removed.

"It's considered inoperable by some urologists and referred to radiation oncology," says Dr. Zincke. "They think surgery can't be done because the cancer is outside the prostate. Currently, only 15 percent are referred for surgery."

The problem with radiation therapy as the first line of treatment for cT3 prostate cancer, according to the Mayo Clinic researchers, is the cancer survival rate, which is 79 percent at only five years. In contrast, with radical prostatectomy, 79 percent of the patients lived at least 15 years. Says Dr. Zincke, "So, obviously surgery does a better job for these patients."

Dr. Zincke also explains that when malignant prostate tumors are high grade -- more aggressive -- they are not especially responsive to radiation therapy alone.

He believes the current trend away from surgery is a disservice to patients. "Patients are being denied surgical treatment when indeed they could have had surgery," Dr. Zincke says.

The cancer survival rates for cT3 prostate cancer with radical prostatectomy not only approach those of cT2 prostate cancer (cancer confined to the prostate), which is 90 percent at 15 years, but they are even more impressive due to the ages of the patients, says Dr. Zincke. "It's significant because the average patient is only 62 years old," he says. "So, a 15-year survival is a long time."

In addition to a favorable survival rate for the cT3 prostate cancer patients studied, the Mayo Clinic researchers also found urinary incontinence rates and complications were akin to those for cT2 prostate cancer.

Some of the patients studied with cT3 prostate cancer had additional, or adjuvant, therapy after surgery, such as hormone therapy or radiotherapy. Dr. Zincke indicates that adjuvant therapy is necessary for patients whose prostate cancer affects the lymph nodes. Surgery alone may be sufficient treatment for those without lymph node involvement. Approximately 50 percent of the cases of cT3 prostate cancer do not involve the lymph nodes.

The study also found that 25 percent of the patients were overstaged -- told that they had a cT3 prostate cancer, a more advanced form, rather than what they really had a cT2 prostate cancer in which the malignancy is confined inside the prostate.

Dr. Zincke points to following patients over 15 years post-treatment as a strength of the study. "The highest incidence of prostate cancer death is not reached until 11 years after treatment, so 15-year data is significant," he says. "In contrast, five-year data is less meaningful."

Dr. Zincke recommends that patients with cT3 prostate cancer seek a surgeon who performs at least one prostate surgery per week and has completed at least 300 prostate surgeries. He explains that currently only 3 to 4 percent of urologists are doing more than one prostate cancer surgery per week. As they seek an appropriate surgeon, he encourages patients that "if someone tells you your cT3 prostate cancer is inoperable, don't give up."

With more common use of prostate-specific antigen (PSA) testing in the United States, more prostate cancers are now caught earlier, before the cancer spreads. Thus, the frequency of cT3 prostate cancers seen at Mayo Clinic has declined to 3 percent of all prostate cancers. Canada and Europe have much higher rates of cT3 prostate cancer, as PSA testing is not conducted as frequently and more cancers are discovered later than in the United States, allowing the cancers more opportunity to spread outside the prostate.

NICE Supports High Intensity Focused Ultrasound (HIFU) for the Treatment of Localized Prostate Cancer

Sun, 03 Apr 2005 09:55:38 PST

( from http://www.rxpgnews.com ) EDAP TMS S.A. (Nasdaq: EDAP - News), today welcomed the publication of the U.K. National Institute for Clinical Excellence (NICE) recent guidelines supporting the use of High Intensity Focused Ultrasound (HIFU) for the treatment of localized prostate cancer.

More than 27,000 men in the U.K. are being diagnosed with prostate cancer every year, and 10,000 die from the disease.

HIFU with Ablatherm® significantly broadens the range of treatment options for patients with localized prostate cancer, offering an alternative therapy for the patients.

It is particularly suited to patients who are not candidates for surgery or those for whom radiotherapy treatment has failed. In contrast to surgery, it requires only a short period of hospitalization and has a low complication rate. Unlike radiation, HIFU treatment can also be safely repeated if necessary.

HIFU with Ablatherm has established strong credentials with 7,000 treatments performed to date worldwide using the Ablatherm. In the U.K., Stepping Hill Hospital, Stockport, was the first institution in the country to use HIFU with Ablatherm for the treatment of prostate cancer. It has been treating patients for more than a year, as part of a clinical pilot trial, with very encouraging outcome.

Dr. Stephen Brown, consultant urologist at Stepping Hill Hospital, Stockport, commented: "In Europe there is increasing experience with many new centers coming on line and large numbers of patients being treated. When we started a year ago we wanted to embark on a U.K. study to establish whether it is as good as the Europeans are claiming. Results so far are very encouraging. Patients seem very happy with the treatment, but it's still very early days."

Hugues de Bantel, Chief Executive Officer of EDAP TMS, added: "We very much welcome these supportive guidelines from NICE. They provide a positive springboard for our continuing efforts to educate both clinicians and patients in the U.K. about the benefits of HIFU with Ablatherm treatment options. Ablatherm is now officially recognized in the U.K."

Surgery, Not Radiotherapy Offers Better Survival Advantage for Stage 3 Prostate Cancer

Sun, 03 Apr 2005 09:38:38 PST

( from http://www.rxpgnews.com ) New findings from Mayo Clinic indicate that cT3 prostate cancer, a disease in which the cancer has spread locally from inside the prostate to immediately outside it, is operable and has 15-year cancer survival rates of almost 80 percent.

"These patients have a better chance if they undergo surgery and are living longer than if they undergo radiation therapy," says Horst Zincke, M.D., Ph.D., Mayo Clinic urologist and senior study investigator.

Treatment of this type of prostate cancer has been controversial, as it is a stage 3 cancer in which the malignancy has spread.

Due to its advanced stage, some physicians have considered it inoperable via radical prostatectomy, according to Dr. Zincke. He explains that many patients come to him for a second opinion after being told their cT3 prostate cancers could not be surgically removed.

"It's considered inoperable by some urologists and referred to radiation oncology," says Dr. Zincke. "They think surgery can't be done because the cancer is outside the prostate. Currently, only 15 percent are referred for surgery."

The problem with radiation therapy as the first line of treatment for cT3 prostate cancer, according to the Mayo Clinic researchers, is the cancer survival rate, which is 79 percent at only five years.

In contrast, with radical prostatectomy, 79 percent of the patients lived at least 15 years. Says Dr. Zincke, "So, obviously surgery does a better job for these patients."

Dr. Zincke also explains that when malignant prostate tumors are high grade -- more aggressive -- they are not especially responsive to radiation therapy alone.

He believes the current trend away from surgery is a disservice to patients. "Patients are being denied surgical treatment when indeed they could have had surgery," Dr. Zincke says.

The cancer survival rates for cT3 prostate cancer with radical prostatectomy not only approach those of cT2 prostate cancer ( cancer confined to the prostate ), which is 90 percent at 15 years, but they are even more impressive due to the ages of the patients, says Dr. Zincke.

"It's significant because the average patient is only 62 years old," he says. "So, a 15-year survival is a long time."

In addition to a favorable survival rate for the cT3 prostate cancer patients studied, the Mayo Clinic researchers also found urinary incontinence rates and complications were akin to those for cT2 prostate cancer.

Some of the patients studied with cT3 prostate cancer had additional, or adjuvant, therapy after surgery, such as hormone therapy or radiotherapy. Dr. Zincke indicates that adjuvant therapy is necessary for patients whose prostate cancer affects the lymph nodes.

Surgery alone may be sufficient treatment for those without lymph node involvement. Approximately 50 percent of the cases of cT3 prostate cancer do not involve the lymph nodes.

The study also found that 25 percent of the patients were overstaged -- told that they had a cT3 prostate cancer, a more advanced form, rather than what they really had a cT2 prostate cancer in which the malignancy is confined inside the prostate.

Dr. Zincke points to following patients over 15 years post-treatment as a strength of the study. "The highest incidence of prostate cancer death is not reached until 11 years after treatment, so 15-year data is significant," he says. "In contrast, five-year data is less meaningful."

Dr. Zincke recommends that patients with cT3 prostate cancer seek a surgeon who performs at least one prostate surgery per week and has completed at least 300 prostate surgeries. He explains that currently only 3 to 4 percent of urologists are doing more than one prostate cancer surgery per week.

As they seek an appropriate surgeon, he encourages patients that "if someone tells you your cT3 prostate cancer is inoperable, don't give up."

With more common use of prostate-specific antigen ( PSA ) testing in the United States, more prostate cancers are now caught earlier, before the cancer spreads. Thus, the frequency of cT3 prostate cancers seen at Mayo Clinic has declined to 3 percent of all prostate cancers. Canada and Europe have much higher rates of cT3 prostate cancer, as PSA testing is not conducted as frequently and more cancers are discovered later than in the United States, allowing the cancers more opportunity to spread outside the prostate.

Socio-Cultural factors play a significant role in Prostate Cancer Treatment Decisions

Mon, 28 Mar 2005 21:04:38 PST

( from http://www.rxpgnews.com ) Researchers say social and cultural factors play a significant role in patients' prostate cancer treatment decisions.

Prostate cancer is now detected earlier than ever because of the introduction of a simple blood test in 1987 called the Prostate Specific Antigen (PSA) test. However, the treatment options for prostate cancer radical prostatectomy, external beam radiation, and brachytherapy have no evidence of clear mortality benefit over expectant treatment (i.e., observation). Moreover, the treatments can lead to serious side effects, including urinary incontinence, impotence, and bowel urgency.

It is widely assumed that men make treatment decisions based on medical considerations, such as age, other existing conditions, and the grade of the tumor. Investigators led by Thomas Denberg, M.D., Ph.D. of the University of Colorado at Denver and Health Sciences Center in Denver reviewed data from 27,920 Hispanic, non-Hispanic, white, and black men without underlying conditions who were registered in the Surveillance, Epidemiology, and End Results (SEER) cancer database.

The investigators found that sociocultural and racial factors independently predicted treatment. Caucasian, black, and Hispanic patients were equally likely to receive curative treatments over "watchful waiting" but while Caucasian and Hispanic men were more likely to choose prostatectomy, black men were more likely to be treated with radiation. Independently, marriage was also an important predictor of treatment: married men in all three groups were much more likely than unmarried men to receive curative treatment over watchful waiting, and they were also more likely than their unmarried counterparts to receive prostatectomy compared with radiation.

The authors summarize, "This study confirmed the hypothesis that sociocultural factors add significant explanatory power to traditional biomedical variables in understanding treatment patterns of early-stage prostate cancer."

New Prostate Cancer Suppressor Gene Found

Wed, 23 Mar 2005 00:27:38 PST

( from http://www.rxpgnews.com ) A gene named ATBF1 may contribute to the development of prostate cancer through acquired mutations and/or loss of expression, according to research at Emory University School of Medicine and its Winship Cancer Institute. The Emory research team was led by Jin-Tang Dong, PhD, associate professor in the Winship Cancer Institute. Lead author was postdoctoral fellow Xiaodong Sun, PhD.

Although previous research has suggested that a section of chromosome 16 harbors a tumor suppressor gene in several types of human cancers, the particular gene responsible has not previously been identified. By studying the genes within the section of chromosome 16, the Emory scientists found that ATBF1 was a strong candidate for an important tumor suppressor gene because its function is frequently lost in prostate cancer through gene mutations and/or loss of expression. In addition, ATBF1 was found to inhibit cell growth in culture dishes. A tumor suppressor gene is a gene whose loss of function contributes to the development of cancer.

ATBF1 is a transcription factor (regulator of gene expression) that functions to regulate the expression of other genes. If its function is impaired by mutations or loss of expression, a cell could lose the control of cancer genes. The Myb oncogene, for example, is normally inhibited by ATBF1, but it can be activated if ATBF1 is lost.

"Sporadic cancers often are the result of multiple genetic alterations that accumulate over time," said Dr. Dong, "but only a small number of genes have been shown to undergo these frequent mutations. Because ATBF1 inhibits cell proliferation, frequent acquired mutations that inhibit the gene, such as the ones we found, could lead to a lack of growth control in prostate cancer. Because gene deletion in chromosome 16 is common in many types of cancer, including lung, head and neck, nasopharynx, stomach, breast, and ovary, ATBF1 could be involved in the development of these cancers as well."

PLCO Trial Reports Baseline Data for Prostate Cancer Screening

Fri, 18 Mar 2005 23:17:38 PST

( from http://www.rxpgnews.com ) The prostate component of the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Trial is designed to determine the impact of annual screening with prostate-specific antigen (PSA) testing and digital rectal exam on mortality from prostate cancer by comparing one group of men who receive screening with a control group of men undergoing routine medical care. In a new study, Gerald L. Andriole, M.D., of the Washington University School of Medicine in St. Louis, and colleagues report findings from the initial round of screening. The final results of the trial are still several years away.

Of the more than 38,000 men in the screening group, 7.5% had a positive digital rectal exam (suspicious for cancer), and 7.9% had a PSA level higher than 4 ng/mL.

Of the men who had positive screening tests, 74.2% underwent additional diagnostic testing, and 31.5% had a prostatic biopsy within a year. Overall, 1.4% of the men in the screening group were diagnosed with prostate cancer, most of which was clinically localized cancer.

Earlier use of Prostate Cancer Vaccines is More Effective

Fri, 18 Mar 2005 22:17:38 PST

( from http://www.rxpgnews.com ) Timing is everything when it comes to killing prostate cancer cells with specially tailored vaccines, say scientists testing the drugs in mice at the Johns Hopkins Kimmel Cancer Center.

"The window of opportunity is narrow for vaccination, designed to reinvigorate the immune system's attack on cancer cells, and it occurs right after hormonal therapy begins to wipe out the tumor and immune cells outnumber cancerous ones," according to Charles Drake, M.D., Ph.D., assistant professor of oncology and director of the research which is published in the March issue of Cancer Cell.

In the Hopkins studies with mice bred to develop prostate cancer, Drake and his collaborators at the University of Connecticut found that the animal's immune system recognizes the cancer but fails to mount an attack, probably because immune cells become tolerant of the slow-growing cancer.

"The mice get used to the cancer very slowly over time," Drake says. "But we found that if we use the vaccine to activate the immune system right after we give the mice hormone therapy to shrink their tumors, T-cells start a reaction against the cancer."

T-cells are responsible for recognizing foreign cells and marking them for destruction. Changes in proteins on the T-cell's surface give clues to whether they "see" the cancer and are targeting it. Those cells that have been ignoring the cancer need time to regroup and multiply in order to mount an attack, the scientists say.

T-cells multiplied three times as much in prostate cancer mouse models that were given vaccinations immediately after hormone therapy as opposed to those not receiving hormone therapy. "It's not immunological magic," Drake notes. "It makes sense that when hormone therapy gets rid of cancer cells and the protein antigens they carry, it's easier to re-educate the immune system to fight cancer cells when they come back in smaller numbers."

"If our findings are confirmed, we believe human vaccines stand a better chance of getting T-cells to respond after most of the tumor is destroyed by hormone therapy," says Drake. "The strategy thereafter would be to continue activating the immune system with repeated vaccines and delay the time until the patient needs more hormone therapy, other treatments or lives old enough to die from other causes."

"Most prostate cancer vaccines currently are tested on men whose cancers are growing and no longer responsive to hormone therapy," says Drake. "Fewer than 20 percent of men respond to vaccines alone." Drugs that suppress male hormones such as testosterone, which fuels prostate cancer, are one of the main treatment alternatives for early relapse and helps stall cancer growth.

No clinical trials are yet available for the earlier vaccine regimen.

Prostate cancer is the leading cause of cancer deaths in American men. The average time to relapse after beginning hormone therapy is approximately two years.

Cholesterol Helps Prostate Tumors Survive and Grow

Fri, 18 Mar 2005 15:23:38 PST

( from http://www.rxpgnews.com ) Researchers at Children's Hospital Boston have demonstrated that high blood cholesterol levels accelerate the growth of prostate tumors, showing that cholesterol helps prostate tumors survive and grow at the molecular level by altering chemical signaling patterns within tumor cells.

The findings, published in the April 1 issue of the Journal of Clinical Investigation (available online March 17), are in keeping with population studies that have linked prostate cancer with high cholesterol levels and Western diets high in cholesterol. The researchers also present evidence that cholesterol-lowering "statin" drugs, now widely used in cardiovascular disease, may inhibit cancer growth.

A team led by Michael Freeman, PhD, Program Director of the Urological Diseases Research Center at Children's, injected human prostate cancer cells into mice and observed tumor growth. When the animals' blood cholesterol was raised by diet, cholesterol accumulated in the outer membranes of the tumor cells, specifically in structures called lipid rafts. Cholesterol elevation in the rafts activated a chemical "cell-survival" pathway known as Akt, thought to be a central pathway in prostate cancer. Activation of Akt enabled the tumor cells to resist chemical cues to commit suicide through the process known as apoptosis, thereby allowing the cancer to proliferate.

Increased cholesterol levels didn't trigger new cancers in the mice, but six weeks after tumor cells were injected, the incidence of tumors was more than doubled in the mice on high-cholesterol diets, and the tumors were markedly larger in size.

"What we're looking at is progression, not initiation of a tumor," says Freeman.

In addition, test-tube studies showed that when the cholesterol-lowering drug simvastatin was used to reduce cholesterol in cell membranes, the Akt pathway was inhibited, apoptosis increased, and tumors stopped proliferating. Replenishing cell membranes with cholesterol reversed this inhibitory effect.

"Our study opens up a new paradigm in thinking about how cancer might be controlled pharmacologically by manipulating cholesterol," says Freeman. "Our data support the notion that cholesterol-lowering drugs -- which are widely used and fairly safe -- might be effective in prevention of prostate cancer, or as an adjunctive therapy."

Although there is some epidemiologic evidence linking high cholesterol levels with certain types of cancer, there has been little research at the cellular level to try to explain why this is so. More recently, epidemiologic studies have begun reporting that people taking cholesterol-lowering drugs have a significantly reduced incidence of prostate and other cancers.

Lipid rafts are structures in the outer cell membrane which Keith Solomon, PhD, a co-investigator on the study and a lipid-raft expert, likens to ice floating on water -- they are dynamic and continually aggregate and disaggregate. They have naturally high concentrations of cholesterol and are believed to be important in cell signaling. Solomon and Freeman believe that cholesterol in the lipid rafts may help sequester proteins involved in cancer pathways in close proximity with each other, facilitating biochemical reactions that promote cancer growth.

An Adoptive Transfer Gene Therapy Technique to Deal with Metastatic Prostate Cancer

Sun, 13 Mar 2005 08:51:38 PST

( from http://www.rxpgnews.com ) Chung Lee, John T. Grayhack, M.D., Professor of Urology at Northwestern University Feinberg School of Medicine, and his laboratory group described the adoptive transfer gene therapy technique in the March issue of Cancer Research.

Lee is also a researcher at The Robert H. Lurie Comprehensive Cancer Center of Northwestern University. The researchers first rendered immune cells known as CD8+ T cells insensitive to transforming growth factor beta ( TGF-beta ), a powerful, naturally occurring substance in the body that enables cancer cells to evade surveillance by the body's immune system. The immunosuppressive effect of TGF-beta in cancer progression is well established.

After inserting a mutated form of the TGF-beta receptor into CD8+ T cells, Lee and associates transplanted the tumor-specific immune cells into mice that had been given a particularly aggressive form of prostate cancer, called TRAMP-C2.

TRAMP-C2 prostate cancer cells produce large amounts of TGF-beta, and possess such potent immunosuppressive power that regular CD8+ T cells are unable to infiltrate tumor tissues, Lee explained.

The mice received a single injection of tumor-reactive TGF-beta-insensitive CD8+ T cells, tumor-specific TGF-beta-sensitive CD8+ T cells or untreated CD8+ T cells at three ( early cancer ), seven or 21 days ( advanced cancer ) after they had been injected with the prostate cancer cells.

Lee and co-researchers found that the tumor-reactive TGF-beta-insensitive CD8+ T cells infiltrated prostate cancer tumors and effectively destroyed the TRAMP-C2 cells.

Moreover, results showed that the CD8+ T cells showed five-fold more tumor-killing activity than that of TGF-beta-sensitive CD8+ T cells and 25-fold more tumor-killing activity over that of untreated CD8+ T cells.

Mice that received adoptive transfer of tumor-reactive TGF-beta-insensitive CD8+ T cells following injection of tumor cells showed no or little evidence that cancer had spread in the body.

Importantly, mice that received TGF-beta-insensitive CD8+ T cells did not develop systemic autoimmune disease, as had been the case in earlier studies by Lee and other researchers.

"To the best of our knowledge, studies to test this concept have not been attempted before," Lee said.

In summary, these CD8+ T cells were specifically reactive against tumor tissues. Second, they were insensitive to TGF-beta. The two properties endowed the CD8+T cells with the ability to infiltrate tumor tissues and function as potent effectors against tumor cells. Finally, these cells were able to persist in tumor-bearing hosts but not in those that are cancer free.

The findings of the Northwestern study provide a proof of principle that an adoptive transfer of tumor-reactive TGF-beta-insensitive CD8+ T cells may warrant consideration for the treatment of advanced tumors, Lee said.

KLF6 variant gene may increase risk of Prostate Cancer by 50%

Thu, 17 Feb 2005 21:34:38 PST

( from http://www.rxpgnews.com ) A single gene variant may increase a man's risk of prostate cancer by 50%, according to a new study led by researchers at Mount Sinai School of Medicine and published this week in Cancer Research.

In 2001, Mount Sinai researchers published a study in Science that showed that a gene, known as KLF6, fails to function properly in at least 50 to 60 percent of all prostate cancers. This was the first single gene shown to be responsible for the majority of cases of this disease, which affects approximately 200,000 men each year.

This finding led to the question as to whether or not mutations in this gene that are present from birth might increase an individuals susceptibility to prostate cancer. John Martignetti, MD, PhD, Assistant Professor of Human Genetics at Mount Sinai and colleagues addressed this question by analyzing differences in the KLF6 gene in 3,411 blood samples from men in registries of three major cancer centers (Johns Hopkins University, the Mayo Clinic and Fred Hutchinson Cancer Research Center). Blood samples were divided into three groups based on the individuals from which they were taken those with prostate cancer who had a family history of prostate cancer, those with prostate cancer and no family history of the disease, and those without prostate cancer.

About 17% of the patients with a family history of the disease and 15% of patients with no such history carried at lease one copy a single KLF6 variant, but only 11% of the controls had a copy. The significant difference in prevalence of the variant among three groups indicates that individuals with this particular gene variant face an approximately 50% increased risk for developing prostate cancer.

In the 2001 study, Dr. Martignetti, Scott Friedman, MD, Fishberg Professor of Medicine and Chief of the Division of Liver Diseases, and Goutham Narla, an MD/PhD student at Mount Sinai discovered that KLF6, functions as a tumor suppressor gene. Its role is to restrict cell growth. When KLF6 fails to function properly cell growth goes unchecked and cancer may results. It has since been discovered that KLF6 defects are implicated in a number of other human cancers, including colorectal, lung and liver.

The variant of the gene investigated in the report published this week produces a an altered version of the KLF6 protein. Rather than entering the cell nucleus to suppress cell growth as the KLF6 protein usually does, this altered version remains in the cytoplasm, where it has the opposite effect, thus increasing cell growth and potentially leading to the development of caner.

Prostate cancer is among the most prevalent cancers worldwide and is the second leading cause of male cancer-related death in the United States. Incidence is expected to double among men over age 65 in the next 25 years, according to the authors. "Our findings highlight a completely novel and previously unexplored pathway for the development of prostate cancer," said Dr. Martignetti. "Ultimately we plan to investigate the potential of this gene as a diagnostic tool, an indicator of a patients risk for prostate cancer, and as a potential target for new treatments."

Oral Phenoxodiol Gets Fast Track Designation for its use in Prostate Cancer

Thu, 27 Jan 2005 16:51:38 PST

( from http://www.rxpgnews.com ) Marshall Edwards, Inc.,today announced that the U.S. Food and Drug Administration (FDA) has granted the investigational anti-cancer drug, phenoxodiol, fast track status for its intended use in patients with hormone- refractory prostate cancer (HRPC).

The successful application for fast track status was based on data derived in a Phase Ib/IIa study, conducted in two Australian hospitals, in which men with late stage HRPC were treated with the oral dosage form of phenoxodiol as a monotherapy.

The preliminary outcome of this study was presented to the American Association of Cancer Research (AACR) conference on Basic, Translational and Clinical Advances in Prostate Cancer in November 2004.In the study, dosages of phenoxodiol ranging from 200mg to 400mg 8-hourly had a significant effect on disease progression, as evidenced by falls in PSA levels, and suppression of those levels for a period of at least 6 months. Most of the patients remain on phenoxodiol therapy for periods up to 18 months without evidence of disease progression.

Of particular relevance to the FDA is that prostatic adenocarcinoma that is refractory to both hormonal therapy and cytotoxic chemotherapy is associated with severe morbidity and a life expectancy of less than 1 year, and as such meets the criteria for a serious and life-threatening disease.

Under the FDA Modernization Act of 1997, designation as a Fast Track product means that the drug for the designated indication is eligible for accelerated marketing approval programs.

"This decision of the FDA underpins our confidence in phenoxodiol being an effective therapy for late-stage prostate cancer. The next step is to take phenoxodiol into a pivotal study where we will test its ability to halt disease progression in men with prostate cancer who have failed the standard treatment of hormone therapy and docetaxel chemotherapy," said Dr. Graham Kelly, Executive Chairman of Marshall Edwards, Inc.

Mr. Christopher Naughton, CEO of Marshall Edwards, Inc., said, "This decision represents a significant endorsement of the potential of phenoxodiol, coming just 2 months after the FDA granted fast track status for phenoxodiol for late-stage ovarian cancer. The Company now has two opportunities to pursue for the continuing development of phenoxodiol for the benefit of both prostate cancer and ovarian cancer patients."

Phenoxodiol in intravenous form was granted fast track status by the FDA in November 2004 for its intended use in patients with recurrent ovarian cancer.

Phenoxodiol is an investigational product that regulates signal transduction pathways in cancer cells resulting in the break down of the intra-cellular proteins -- XIAP (X-linked Inhibitor of Apoptosis Protein) and FLIP (Fas Ligand Inhibitory Protein) -- that block the ability of the cancer cell to undergo apoptosis via the death receptor mechanism.(1) While these proteins play a vital role in preventing unintentional cell death in healthy cells, they are over-expressed in many forms of cancer, as well as being associated with the development of resistance to anti-cancer drugs.

Phenoxodiol works selectively on tumor cells, thought to be due to its interaction with the enzyme, tumor-specific NADH oxidase, which is restricted to cancer cells. Clinical trials to date have revealed no significant drug related adverse side effects. Phenoxodiol is an investigational drug and, as such, is not approved for marketing in the United States.

Prostate cancer is one of the most common types of cancer among men in Western countries. The American Cancer Society estimates there will be 232,000 new cases of prostate cancer in the United States in 2005 and that about 30,350 men will die of this disease. Prostate cancer is strongly associated with the male sex hormone, testosterone, and most early cases of prostate cancer respond for some time to hormonal therapy that blocks the ability of testosterone to stimulate the cancer. However, the majority of cases of prostate cancer eventually become independent of testosterone, at which time they are known as hormone-refractory prostate cancer (HRPC). The cancer at this stage typically is metastatic, with a patient survival time typically in the range of 1 to 2 years.

The FDA recently approved the combination of docetaxel (Taxotere(R)) and prednisone for the treatment of HRPC. That combination produced an overall increase in survival of 10 weeks (from an average of 16.4 months to an average of 18.9 months).

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Phenoxodiol has been developed by Novogen Limited , an Australian biopharmaceutical company that is specializing in the development of therapeutics based on the diphenolic ring structure. Novogen, based in Sydney, Australia, is developing a range of therapeutics across the fields of oncology, cardiovascular disease and inflammatory diseases.

Marshall Edwards, Inc. has licensed from Novogen Limited the rights to bring phenoxodiol to the global market.

Innovative planning techniques to help men with prostate cancer avoid erectile dysfunction after radiation treatment.

Fri, 07 Jan 2005 00:58:38 PST

( from http://www.rxpgnews.com ) Researchers at the University of Michigan Comprehensive Cancer Center are using innovative planning techniques to help men with prostate cancer avoid erectile dysfunction after radiation treatment.

By using MRI scans in addition to CT scans, radiation oncologists can identify the blood vessels that control erectile function and plan treatment to target the prostate more precisely, sparing those nearby vessels. Results from an initial study with 25 patients appear in the January issue of the International Journal of Radiation Oncology Biology Physics.

Some 230,000 men were diagnosed with prostate cancer in 2004. While it's more common in older men, a growing number of men are being diagnosed in their 50s.

"As we treat younger men, erectile function is an important concern. We're often treating men in their 50s, and this is a very important issue for them. Most of the men I see are going to be cured. Once you start curing cancers at an extremely high rate, then the focus moves to quality of life," says Patrick W. McLaughlin, M.D., clinical professor of Radiation Oncology at the University of Michigan Medical School and director of Providence Hospital Radiation Oncology, with cancer centers in Southfield and Novi, both affiliated with the U-M Comprehensive Cancer Center.

Treatment for prostate cancer can involve surgery to remove the prostate or radiation therapy. During surgery, the nerves that control erectile function may be severed â which has led to new surgical techniques to avoid cutting those nerves.

But doctors are less sure what causes erectile dysfunction after radiation therapy. Erectile dysfunction among men without prostate cancer is most commonly caused by a problem in the blood vessels, and doctors do know that radiation causes obstruction of the vessels that fall within the treatment area. Using that as a starting point, the U-M team began investigating radiation-related erectile dysfunction as a blood vessel problem.

Typically, radiation oncologists rely on a CT scan to identify the prostate and plan treatment. But because of limitations in the CT scan, the images do not show the bottom of the prostate. Doctors instead estimate where the prostate ends, based on average distance from identifiable structures. The U-M study, using MRI in addition to CT scans to get a better picture of the whole prostate, found the distance between the prostate and the penile bulb ranged from 0.5 cm to 2.0 cm.

"We condemned one of the common tricks people try to use. By assuming an average distance of 1.5 cm between the prostate and the penile bulb, either you're going to treat way more than you need to or you're going to miss the prostate," McLaughlin says.

By taking the additional imaging, the U-M team was able to plan treatment to include the entire prostate but avoid the critical blood vessels below. Preliminary results suggest that avoiding the vessels prevents erectile dysfunction.

"Because we can't see any detail of this area on CT scans, we just assume if we treat below the prostate it's no big deal. But it is a big deal. There is no cancer below the prostate, but there are critical structures related to erectile function as well as urine sphincter function. Treating below the prostate may result in needless problems," McLaughlin says. "I don't have much doubt from what I've seen that this approach is likely to have huge impact."

About one in two men who undergoes radiation therapy for prostate cancer is unable to have sex five years later unless Viagra or similar medications are used.

In addition, the vessels involved in erectile function also play a role in bowel and bladder control. The researchers suspect avoiding radiation to these areas will improve other quality of life issues, such as urinary leakage and bowel problems.

In addition to McLaughlin, U-M study authors were Vrinda Narayana, Ph.D., adjunct clinical assistant professor of Radiation Oncology; Amichay Meriowitz, M.D., Sara Troyer, Peter Roberson, Ph.D., Howard Sandler, M.D., Lon Marsh, Theodore Lawrence, M.D., and Marc Kessler, Ph.D. Narayana is also affiliated with the Providence Cancer Center. Roger Gonda Jr., M.D., from Providence Hospital's Department of Radiology is also a study author.

Combining Hormones with External, Internal Radiation Helps High Risk Prostate Cancer Patients

Thu, 30 Dec 2004 17:34:38 PST

( from http://www.rxpgnews.com ) Prostate cancer patients with high risk cancers who are treated with both internal and external radiation and hormone treatment have a better chance of beating the disease than patients treated with radiation alone, according to a new study published in the January 1, 2005, issue of the International Journal of Radiation Oncology*Biology*Physics, the official journal of ASTRO, the American Society for Therapeutic Radiology and Oncology.

Since the late 1980s, doctors have been increasingly using internal radiation, also called radioactive seed implants or brachytherapy, to cure prostate cancer. For patients with higher risk prostate cancers defined as having at least two of the following three: a high Gleason score, a high PSA score and/or an advanced stage doctors have been adding hormone therapy and external beam radiation therapy to the treatment plan to try to increase survival rates. In this study, doctors studied nearly 200 men with high risk prostate cancer over eight years to see if adding external beam radiation and hormone therapy to brachytherapy did indeed increase disease-free survival rates.

Of the participating patients, 107 men were treated with external beam radiation therapy combined with seed implants. Another 69 patients received hormone therapy in addition to the seed implants and external beam radiation. After eight years, nearly 94 percent of the men who had hormone therapy in addition to the two types of radiation had no evidence of their prostate cancer, compared with 84 percent of the men who only had seed implants and external beam radiation therapy.

This is an exciting study because it shows that adding hormone treatment and external beam radiation therapy to seed implants does indeed help men with high risk prostate cancer to live longer without the cancer returning, said Gregory S. Merrick, M.D., lead author of the study and a radiation oncologist at Schiffler Cancer Center in Wheeling, W.Va.

Alternative immunotherapy for prostate cancer bone lesions

Thu, 16 Dec 2004 17:56:38 PST

( from http://www.rxpgnews.com ) Prostate cancer (PC) is the most commonly diagnosed malignancy and the second leading cause of death in American men. PC usually moves into the bone and the symptoms are treated by suppression of the production of male hormones known as androgens. However within 12-18 months of beginning this therapy, the disease usually becomes androgen-independent and no further effective therapies currently exist.

In the December 15 issue of the Journal of Clinical Investigation, Zelig Eshhar and colleagues from The Weizmann Institute of Science, Israel, report an alternative treatment approach. The authors used the "T body" approach, in which T cells genetically reprogrammed to be tumor antigenspecific were directly applied to confined but well-established PC tumors in mice. These mice were "preconditioned" prior to treatment, meaning that they were subjected to low-dose radiation or chemotherapy prior to T cell transfer in order to prevent the body from attacking the newly transferred T cells. The "T body" approach decreased tumor growth, prolonged survival, and even cured the treated mice. The authors suggest that patient preconditioning prior to the transfer of tumor-specific T cells offers great promise for immunotherapy of metastatic PC and other malignant tumors.