RxPG News : Pancreatic Cancer

Multimodality approach beneficial even in advanced cancers

Thu, 13 Mar 2008 05:49:50 PST

( from http://www.rxpgnews.com ) The article published in volume 14 issue 6 of World Journal of Gastroenterology reports on one patient who presented to Dr Cosimo Sperti of University of Padua, Padova, Italy, in 2001 after an exploratory laparotomy performed in another hospital for an unresectable pancreatic cystic mass that had infiltrated the portal vein. Total pancreatectomy together with resection and reconstruction of portal vein was then successfully performed. Histopathologic examination showed a solid-pseudopapillary tumor of the pancreas infiltrating the layer of the portal vein.

Thirty-two months later, multiple hepatic metastases occurred. Percutaneous biopsy confirmed hepatic localization of solid-pseudopapillary tumor of the pancreas. The patient underwent multiple chemotherapeutic regimens that have resulted in a substantially stable disease until the present time, 75 months after the initial pancreatic resection.

To better understand the impact of surgery and chemotherapy on the prognosis of this rare tumor, Dr. Cosimo Sperti reviewed 25 patients from medical English literature with infiltrating solid-pseudopapillary neoplasm of the pancreas. Treatment of metastatic disease was also analyzed.

On the basis of the present case and the published literature, Dr. Cosimo Sperti has proposed the indications of aggressive surgery, whenever possible, even in advanced tumors, and in centers with high volume of pancreatic surgery. Although standard chemo-radiotherapeutic regimens do not exist, a multimodality approach (i.e. surgery, chemotherapy and/or radiotherapy) may offer long-term survival prospects even in dealing with advanced tumors.

Gemcitabine delays progression of operable pancreatic cancer

Sat, 29 Sep 2007 13:20:37 PST

( from http://www.rxpgnews.com ) Giving pancreatic cancer patients the chemotherapy drug gemcitabine after surgery delays progression of the disease by about six months, according to new research by Japanese scientists.

The study, presented today (Thursday) at the European Cancer Conference (ECCO 14) in Barcelona, found that the drug more than doubled the average disease-free survival from 4.9 months to 11.4 months.

?We believe that a median disease-free survival of 11.4 months is an outstanding result. It means an improvement, or reduction in the risk of recurrence, of 41 percent,? said the study?s lead researcher, Dr Tomoo Kosuge, deputy director of the National Cancer Center Hospital in Tokyo, Japan. ?That is difficult to achieve in patients with pancreatic cancer.?

Pancreatic cancer has among the poorest prognoses. Most often, it has already spread by the time it is diagnosed, but in about 20 percent of patients, surgery is a viable option. However, even if it can be operated on, the cancer normally recurs and more than half of patients die within 20 months of their diagnosis. Only around 20 percent of them are still alive five years after being diagnosed.

Chemotherapy with gemcitabine is the standard treatment for advanced pancreatic cancer that cannot be operated on. As for resectable pancreatic cancer, researchers are investigating whether chemotherapy or chemoradiation might help. However, there is no universally accepted adjuvant treatment for patients whose pancreas can be removed, so mere observation after surgery is still the widely accepted approach.

In the latest study, 118 patients whose pancreatic cancer could be cut out were either given gemcitabine chemotherapy after surgery or closely monitored by doctors. Both groups were followed for more than 20 months.

The disease recurred in 72 percent of the patients getting gemcitabine, compared with 85 percent of those on observation. The overall survival, meaning survival regardless of whether the disease progressed, was better in the gemcitabine group, but those results were not statistically significant.

?In the results of our study, the lack of a significant difference in the overall survival means the observation approach was not altogether negated. We therefore propose that chemotherapy with gemcitabine, as well as observation, now be considered as optimal treatment for patients with operable pancreatic cancer,? Kosuge said.

The Japanese study bolsters the findings of a German study published earlier this year that similarly found gemcitabine delays progression of the disease after surgery.

TG2 shields pancreatic cancer cells from self-destruction

Mon, 19 Mar 2007 22:57:40 PST

( from http://www.rxpgnews.com ) An overexpressed protein protects human pancreatic cancer cells from being forced to devour themselves, removing one of the body's natural defenses against out-of-control cell growth, researchers at The University of Texas M. D. Anderson Cancer Center report in the March issue of Molecular Cancer Research.

The protein tissue transglutaminase, known by the abbreviation TG2, previously has been found by researchers at M. D. Anderson and elsewhere to be overexpressed in a variety of drug-resistant cancer cells and in cancer that has spread from its original organ (metastasized).

"In general, you rarely see overexpression of TG2 in a normal cell," says Kapil Mehta, Ph.D., professor in the M. D. Anderson Department of Experimental Therapeutics, who began 10 years ago studying TG2 as an inflammatory protein.

Mehta and colleagues in the past year have connected TG2 overexpression to drug-resistant and metastatic breast cancer, pancreatic cancer and melanoma.

Expression of TG2 is tightly regulated in a healthy cell, Mehta says, and is temporarily increased in response to certain hormones or stress factors. "However, constitutive expression of this protein in a cancer cell helps confer protection from stress-induced cell death," Mehta says. "We are developing TG2 as a pharmaceutical target and are now working with a mouse model to that end."

The mechanisms by which TG2 might promote drug-resistance and metastasis have remained elusive, the researchers note. In this paper, the M. D. Anderson team shows in lab experiments that inhibiting the protein in pancreatic cancer cells leads to a form of programmed cell suicide called autophagy, or self-digestion.

TG2 was inhibited in two separate ways. First, the researchers blocked another protein known to activate TG2. Secondly, they also directly targeted TG2 with a tiny molecule known as small interfering RNA tailored to shut down expression of the protein.

In both cases, the result was a drastic reduction of TG2 expression (up to 94 percent) and telltale signs of autophagy in the cancer cells, which became riddled with cavities called vacuoles.

When autophagy occurs, a double membrane forms around a cell organ, or organelle. This autophagosome then merges with a digestive organelle called a lysosome and everything inside is consumed, leaving the vacuole and a residue of digested material. If enough of this happens, the cell dies.

Gabriel Lopez-Berestein, M.D., professor of experimental therapeutics and study co-author, notes that the research also shows that the self-consuming cell death prevented by TG2 is independent of a prominent molecular pathway also known to regulate autophagy called the mammalian target of rapamycin.

"Targeting TG2, or its activating protein PKC, or both, presents a novel and potentially effective approach to treating patients with pancreatic cancer," Lopez-Berestein said. Research in the mouse model remains in the early stages, the researchers caution.

The researchers also show that the TG2 pathway also is separate from another, better known, form of programmed cell death called apoptosis.

Apoptosis, like autophagy, is a normal biological defense mechanism that systematically destroys defective cells by forcing them to kill themselves. In apoptosis, the cells die via damage to their nucleus and DNA, with other cellular organelles preserved. Autophagy kills by degrading those other organelles while sparing the nucleus.

Mehta's lab reported in a Cancer Research paper last September that TG2 overexpression also activates a protein called nuclear factor-kB known to play a role in regulating cell growth, metastasis and apoptosis. This pathway, Mehta explained, could make TG2 an attractive target for other forms of cancer as well.

Liverpool to trial new pancreatic cancer therapy

Thu, 15 Mar 2007 06:08:15 PST

( from http://www.rxpgnews.com ) Patients in Liverpool are to trial a new therapy for pancreatic cancer a disease which sees most sufferers die within a year of diagnosis.

One of the 10 most common cancers in the UK, it is among the most difficult to diagnose and treat and kills around 7,000 people each year. There are very few early symptoms so most patients present late and only around 15% are suitable for surgery.

The Phase III TeloVac trial has been designed by the Pancreatic Cancer Clinical Sub-Group of the UK National Cancer Research Institute and will be run by Cancer Research UKs Liverpool Cancer Trials Unit.

Funded by Cancer Research UK, the trial will test the vaccine GV1001 alongside two chemotherapy drugs gemcitabine and capecitabine on patients with locally advanced and metastatic pancreatic cancer. GV1001 is a new immunotherapeutic drug for pancreatic cancer developed by Danish-based biotech company Pharmexa.

One of the trials two principal investigators, Professor John Neoptolemos, based at the University of Liverpool and a consultant surgeon at the Royal Liverpool University Hospital, said: "The National Cancer Research Institute is very committed to this trial and is focusing a great deal of energy on recruiting patients to take part in it. This is because we firmly believe that GV1001 could play a key role in the future treatment of pancreatic cancer."

He added: "Were proud to manage this fundamental trial at the Liverpool Cancer Trials Unit and we hope other centres in the UK will participate in order to achieve maximum benefit for patients suffering from locally advanced and metastatic pancreatic cancer."

Chief Investigator Dr Gary Middleton from the Royal Surrey County Hospital, who is working alongside Professor Neoptolemos and Professor David Cunningham from the Royal Marsden Hospital, said: "We believe the future treatment of pancreatic cancer, as well as many other cancers, will include combinations of various chemotherapies together with biological and targeted therapies.

"GV1001 is a particularly attractive vaccine; the antigen that it targets is expressed on virtually all pancreatic cancer cells and the vaccine stimulates the production of all of the cells that are required for an effective immune attack upon these cancers. Adding it to the platform of chemotherapy is an exciting strategy which, if successful, would create a new standard of care in this disease."

Professor John Toy, Medical Director at Cancer Research UK, said: "New treatments are desperately needed for pancreatic cancer as survival rates are so poor. GV1001 is a new generation of agent that harnesses the bodys own immune system to fight cancer. We are delighted to be funding a trial of such an innovative treatment."

Patients with non-resectable pancreatic cancer will be randomly distributed into one of three arms of the trial:

370 patients will be treated with gemcitabine and capecitabine in a standard treatment
370 patients will be treated first with gemcitabine and capecitabine for eight weeks, following which they will be treated with GV1001
370 patients will be treated with gemcitabine and capecitabine and with GV1001 at the same time

The research team aims to find whether the patients treated with a combination of GV1001 and chemotherapy live longer than patients who only receive chemotherapy. It is not expected that GV1001 will cure patients, but that treatment will prolong their lives and that a small proportion of the patients may experience significantly longer survival.

Vitamin D May Cut Pancreatic Cancer Risk by Nearly Half

Wed, 13 Sep 2006 11:59:37 PST

( from http://www.rxpgnews.com ) Consumption of Vitamin D tablets was found to cut the risk of pancreatic cancer nearly in half, according to a study led by researchers at Northwestern and Harvard universities.

The findings point to Vitamin Ds potential to prevent the disease, and is one of the first known studies to use a large-scale epidemiological survey to examine the relationship between the nutrient and cancer of the pancreas. The study, led by Halcyon Skinner, Ph.D., of Northwestern, appears in the September issue of Cancer Epidemiology Biomarkers & Prevention.

The study examined data from two large, long-term health surveys and found that taking the U.S. Recommended Daily Allowance of Vitamin D (400 IU/day) reduced the risk of pancreatic cancer by 43 percent. By comparison, those who consumed less than 150 IUs per day experienced a 22 percent reduced risk of cancer. Increased consumption of the vitamin beyond 400 IUs per day resulted in no significant increased benefit.

Because there is no effective screening for pancreatic cancer, identifying controllable risk factors for the disease is essential for developing strategies that can prevent cancer, said Skinner. Vitamin D has shown strong potential for preventing and treating prostate cancer, and areas with greater sunlight exposure have lower incidence and mortality for prostate, breast, and colon cancers, leading us to investigate a role for Vitamin D in pancreatic cancer risk. Few studies have examined this association, and we did observe a reduced risk for pancreatic cancer with higher intake of Vitamin D.

Skinner, currently in the Department of Population Health Sciences at the University of Wisconsin School of Medicine and Public Health, and his colleagues analyzed data from two long-term studies of health and diet practices, conducted at Harvard University. They looked at data on 46,771 men aged 40 to 75 years who took part in the Health Professionals Follow-up Study, and 75,427 women aged 38 to 65 years who participated in the Nurses Health Study. Between the two studies, they identified 365 cases of pancreatic cancer. The surveys are considered valuable for their prospective design, following health trends instead of looking at purely historical information, high follow-up rates and the ability to enable researchers like Skinner to incorporate data from two independent studies.

Pancreatic cancer is a rapidly fatal disease and the fourth-leading cause of death from cancer in the United States. This year, the American Cancer Society estimates that 32,000 new cases of cancer will be diagnosed. About the same number of people will die this year from the disease. It has no known cure, and surgical treatments are not often effective. Except for cigarette smoking, no environmental factors or dietary practices have been linked to the disease.

In addition to Vitamin D, the researchers also measured the association between pancreatic cancer and the intakes of calcium and retinol (Vitamin A). Calcium and retinol intakes showed no association with pancreatic cancer risk, although retinol is an antagonist of Vitamin Ds ability to influence mineral balances and bone integrity. For that reason, further research is necessary to determine if Vitamin D ingestion from dietary sources, like eggs, liver and fatty fish or fortified dairy products, or through sun exposure might be preferable to multi-vitamin supplements, which contain retinol.

The potential benefits of vitamin D for pancreatic cancer were only recently established by other laboratory studies. Normal and cancerous pancreas tissue contain high levels of the enzyme that converts circulating 25-hydroxyvitamin D into 1,25-dihydroxyvitamin D, the vitamins active form. Other studies have shown an anti-cell proliferation effect of 1,25-dihydroxyvitamin D, potentially inhibiting tumor cells.

In concert with laboratory results suggesting anti-tumor effects of Vitamin D, our results point to a possible role for Vitamin D in the prevention and possible reduction in mortality of pancreatic cancer. Since no other environmental or dietary factor showed this risk relationship, more study of Vitamin Ds role is warranted, Skinner said.

Post operative gemcitabine combination therapy improves survival in pancreatic cancer

Mon, 05 Jun 2006 16:40:37 PST

( from http://www.rxpgnews.com ) Adding the cancer-fighting drug gemcitabine to standard therapy after surgery significantly improves survival for patients with the most common form of pancreatic cancer, according to a new multicenter study led by a University of Maryland radiation oncologist.

More than 500 patients at 128 institutions across the country, including the University of Maryland Marlene and Stewart Greenebaum Cancer Center, were enrolled in the federally funded study from 1998 to 2002.

Thirty-two percent of study participants with "pancreatic head adenocarcinoma" (cancer of the head, or wider part, of the pancreas) were still alive three years after diagnosis after having surgery and being treated with gemcitabine, another chemotherapy drug called 5-fluorouracil (5-FU) and radiation therapy. That compares to a 21 percent three-year survival rate for patients who received 5-FU and radiation treatments alone following their surgery.

"The addition of gemcitabine to the standard postoperative treatment increased patients' survival by 50 percent, which is a significant improvement. We believe these findings will provide a new standard for treating patients with this devastating disease," says the principal investigator, William F. Regine, M.D., professor and chairman of the Department of Radiation Oncology at the University of Maryland School of Medicine and chief of radiation oncology at the University of Maryland Medical Center.

Dr. Regine adds that that the study will serve as a basis for additional research that may lead to more effective treatments for pancreatic cancer. Even with the new combination therapy, the median survival for patients in the study who received gemcitabine was 20.6 months compared to 16.9 months for the patients who had the standard therapy. Median survival is the point at which half of the patients in each group are still living.

Cancer of the pancreas, a large gland just behind the stomach that produces digestive juices and insulin, is the fourth leading cause of cancer death in the United States, with 32,000 people dying of the disease each year. Only 4 percent of people are still living five years after they are diagnosed. Surgery is the treatment of choice for long-term survival, but less than 15 percent of patients are eligible because the disease is usually diagnosed at an advanced stage.

Dr. Regine says that even after having surgery, patients often experience a recurrence of the cancer in the pancreas or in the liver, and treatment options are limited.

"Since the 1990s, the standard of care for patients who have had surgery has been postoperative treatment with the chemotherapy drug 5-FU and radiation. We wanted to find out if adding gemcitabine would boost survival for these patients," Dr. Regine says. He notes that the drug has been used as a first-line treatment for patients with advanced pancreatic cancer who are not eligible for surgery. Gemcitabine interferes with the growth of cancer cells and is used to treat cancer of the breast, pancreas and lung. It belongs to a group of medicines called antimetabolites.

Although the new combination therapy increased survival for patients with pancreatic head cancer, researchers did not see any benefit for patients with cancer in other parts of the gland. Eighty-five percent of pancreatic cancers are located in the head of the pancreas. Surgery to remove this type of tumor, along with the entire pancreas head, part of the small intestine and other nearby tissue, is called the Whipple procedure.

Researchers also found that although gemcitabine lowered patients' white blood cell counts, and consequently their ability to fight infection, oncologists could manage this side effect, and most of the patients were still able to complete the chemotherapy and radiation treatments.

Treatment of pancreatic carcinoma by adenoviral mediated gene transfer of vasostatin in mice

Tue, 15 Nov 2005 15:09:38 PST

( from http://www.rxpgnews.com ) A gene responsible for the production of a protein called vasostatin may prove a promising new way of treating pancreatic cancer, suggests research published ahead of print in Gut.

Pancreatic cancer is the fifth leading cause of cancer deaths in the developed world, and is extremely difficult to treat. Only 3% of affected patients are still alive five years after diagnosis, a survival rate that has remained static for the past three decades.

Currently, the only viable treatment is surgery. Radiotherapy and chemotherapy have little impact on the disease.

The research team investigated the potential of the protein vasostatin to suppress the development of new blood vessels and pancreatic tumour cells both in test tubes and in mice with pancreatic cancer.

'Solid' tumours, such as pancreatic cancer, are heavily dependent on a rich blood supply to enable them to grow rapidly and spread throughout the body. This process is known as angiogenesis.

The protein gene was incorporated into a virus (adenovirus), so that it would be able to penetrate the cells, acting as a vector.

The test tube experiments showed that 72 hours after infection with the genetically modified virus, vasostatin was clearly active in the tissue. Tumour growth in the mice was also curbed, and when compared with mice which had not been infected with the virus, the difference between the two groups was highly significant.

The researchers then looked more closely at the pancreatic cells and the cell linings of the blood vessels (vascular endothelial cells).

They found that although vasostatin seemed to have little impact on the pancreatic cells, it blocked the formation of new blood vessels, effectively cutting off the supply of nutrients to the malignant cells. This effect was seen in both the test tube and animal experiments.

This type of gene therapy "may be a potent strategy to treat many malignant tumours, including pancreatic cancer, and represents a promising therapeutic option for malignancy with a poor prognosis," conclude the authors.

FDA Approves Tarceva for Advanced Pancreatic Cancer

Tue, 08 Nov 2005 16:28:38 PST

( from http://www.rxpgnews.com ) Tarceva (erlotinib), the only EGFR-inhibitor to have shown a survival benefit in lung cancer, will now benefit patients with advanced pancreatic cancer following FDA approval in the United States. Pancreatic cancer is one of the most aggressive forms of the disease and kills more people within the first year than any other cancer. Tarceva is the first new treatment in a decade that has shown a significant improvement in overall survival (23%) when added to chemotherapy (1).

Earlier in October, Roche submitted a Marketing Authorisation Application to the European health authorities for Tarceva to be used in combination with gemcitabine chemotherapy for the first-line treatment of patients with advanced pancreatic cancer.

"Pancreatic cancer is a devastating disease, and with Tarceva patients will receive a treatment which offers survival benefits," said William M. Burns, CEO Division Roche Pharma. "We are pleased by the decision from the FDA and are committed to work with health authorities to make Tarceva available to patients elsewhere."

Pancreatic cancer is the fifth leading cause of cancer deaths in the developed world (2) and is the tenth most frequently occurring cancer in Europe (3) with a death rate of approximately 78,000 people per year (4). Pancreatic cancer is difficult to treat, as it is often resistant to chemotherapy and radiotherapy, and tends to spread quickly to other parts of the body, leading to its high mortality and short life expectancy.

"Improvements in therapy in advanced pancreatic cancer have been very difficult to come by. As a molecularly targeted agent, erlotinib has been shown to add a survival benefit when combined with gemcitabine for patients facing pancreatic cancer," said Dr. Malcolm Moore, study chair and medical oncologist at Princess Margaret Hospital in Toronto, Canada, and Chair of the Gastrointestinal Disease Site, NCIC Clinical Trials Group. "Erlotinib represents a notable step forward for patients and healthcare providers in a disease with a very poor prognosis."

Phase III Studies Show Clear Advantages for Tarceva

Both the FDA approval and EU filing for Tarceva in pancreatic cancer are based upon the results of the pivotal Phase III randomised study (PA3)1 of 569 patients conducted by the National Cancer Institute of Canada Clinical Trials Group based at Queen's University. The double blind study evaluated Tarceva's efficacy in patients with locally advanced or metastatic pancreatic cancer.

The results of PA31 demonstrated the following:

- Treatment with Tarceva plus gemcitabine in patients with advanced pancreatic cancer resulted in significantly longer survival compared to gemcitabine alone (23%)

- 24% of patients receiving Tarceva plus gemcitabine were alive after one year, compared to 19% on gemcitabine alone

- Patients receiving Tarceva plus gemcitabine experienced significantly longer progression-free survival

- Tarceva plus gemcitabine was well tolerated by patients with no increase in haematological toxicity; Rash and diarrhoea were the principal Tarceva-related side effects seen in the study and were generally characterised as mild-to-moderate

- Tarceva plus gemcitabine reported a safety profile generally consistent with that seen in other studies both monotherapy and combination settings

The FDA has approved Tarceva plus gemcitabine chemotherapy for the treatment of locally advanced, inoperable or metastatic pancreatic cancer.

About Tarceva

Tarceva is a small molecule that targets the human epidermal growth factor receptor (HER1) pathway. HER1, also known as EGFR, is a key component of this signalling pathway, which plays a role in the formation and growth of numerous cancers. Tarceva blocks tumour cell growth by inhibiting the tyrosine kinase activity of the HER1 signalling pathway inside the cell.

Tarceva is also approved in the US and across the European Union for patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) after failure of at least one prior chemotherapy regimen.

Tarceva is currently being evaluated in an extensive clinical development programme by a global alliance among OSI Pharmaceuticals, Genentech, and Roche, focussing on earlier stages of NSCLC. Additionally, Tarceva is being studied in combination with Avastin in NSCLC. Trials are also being conducted with Tarceva in other solid tumours, such as ovarian, bronchioloalveolar (BAC), colorectal, pancreatic, head and neck and glioma (brain). Chugai is pursuing its development and regulatory approval for the Japanese market.

Xeloda Dramatically Extends Survival Rates in Pancreatic Cancer

Tue, 08 Nov 2005 15:27:38 PST

( from http://www.rxpgnews.com ) - First Xeloda data to show survival benefit in this deadly cancer

The interim analysis of one of the largest phase III studies investigating the first-line treatment of advanced pancreatic cancer shows that adding Xeloda(R) (capecitabine) to standard chemotherapy (gemcitabine) significantly extends patient survival. The study showed that after a year, 1 patient out of 4 was still alive when treated with Xeloda plus standard chemotherapy compared to 1 in 5 taking standard chemotherapy alone. These remarkable findings were unveiled for the first time at the European Cancer Conference (ECCO) in Paris today.

"These data are very exciting and give new hope for pancreatic cancer sufferers who in general have a very short life expectancy," said Professor John Neoptolemos, Surgical Oncologist, Division of Surgery and Oncology, at the Royal Liverpool University Hospital. "Since the study began in May 2002, I have more patients who are still alive on the Xeloda combination after 12 months and longer - I have never seen so many patients achieve this before," he added.

Pancreatic cancer is one of the most aggressive forms of cancer and is the fifth leading cause of all cancer deaths in the developed world. Approximately 78,000 new cases of pancreatic cancer are diagnosed per year in Europe and 30,000 new cases in the US.(1) Very few treatment options exist.

Lead investigator, Professor David Cunningham said, "This is the first time that adding another cytotoxic drug to gemcitabine has improved the outcome for patients with inoperable pancreatic cancer and the trial results are therefore an important milestone. The combination of gemcitabine and capecitabine should now be considered one of the standard options for patients with advanced pancreatic cancer."

"The encouraging Xeloda data provide further survival benefit and quality of life for patients with this deadly disease and very limited treatment options. The latest results come on top of the recent positive recommendation by the FDA for Tarceva in pancreatic cancer. In addition, Roche has initiated studies with Avastin in this disease," commented William M. Burns, CEO Roche Pharma. "We have also filed Tarceva in pancreatic cancer in the European Union and other countries world-wide."

Notes to Editors:

This randomised study, funded and designed by Cancer Research UK, compared the survival of gemcitabine with gemcitabine plus Xeloda and involved 533 previously untreated patients with locally advanced or metastatic pancreatic cancer. Patients receiving the combination therapy lived significantly longer than those with standard therapy alone (median survival 7.4 vs. 6 months, HR= 0.80) with acceptable levels of toxicity. A higher percentage of patients were alive at 12 months in the group treated with Xeloda plus gemcitabine, compared to those treated with chemotherapy alone (26% v 19%).

About Xeloda

Xeloda is licensed in more than 90 countries worldwide including the EU, USA, Japan, Australia and Canada.

Roche received marketing authorisation for Xeloda as a first-line monotherapy (by itself) in the treatment of metastatic colorectal cancer (colorectal cancer that has spread to other parts of the body) in most countries (including the EU and USA) in 2001. Xeloda has also been approved by the European Medicines Agency (EMEA) and U.S. Food and Drug Administration (FDA) for adjuvant (post-surgery) treatment of colon cancer in March and June 2005, respectively.

Xeloda is licensed in combination with Taxotere(R) (docetaxel) in women with metastatic breast cancer (breast cancer that has spread to other parts of the body) and whose disease has progressed following intravenous (i.v.) chemotherapy with anthracyclines. Xeloda monotherapy is also indicated for treatment of patients with metastatic breast cancer that is resistant to other chemotherapy drugs such as paclitaxel and anthracyclines. Xeloda is licensed for the first-line treatment of stomach cancer that has spread, in South Korea.

Red Meat Associated With Pancreatic Cancer Risk

Wed, 05 Oct 2005 04:38:38 PST

( from http://www.rxpgnews.com ) High consumption of red and processed meats--but not fat or cholesterol--is associated with an increased risk of pancreatic cancer, according to a new study.

Nearly 32,000 Americans were diagnosed with pancreatic cancer last year, and most of them will die from the disease. The 5-year survival rate is less than 5%. Identification of risk factors for the disease has become a part of prevention efforts. Some dietary studies have identified meat, dairy product, and egg consumption as potential risk factors, but the results have been mixed.

To investigate associations between intake of meat, other animal products, fat, and cholesterol and pancreatic cancer risk, Ute Nöthlings, Dr.P.H., of the Cancer Research Center of Hawaii in Honolulu, and colleagues analyzed data from the prospective Multiethnic Cohort Study. During 7 years of follow-up, 482 cases of pancreatic cancer were diagnosed among the more than 190,000 participants.

Participants in the highest quintile of processed meat intake had a 68% increased risk of pancreatic cancer compared with those in the lowest quintile. The yearly incidence rate of pancreatic cancer was 41.3 cases per 100,000 people in the highest quintile compared with 20.2 cases per 100,000 in the lowest quintile. Intakes of pork and red meat were both associated with 50% increased risks of pancreatic cancer when comparing the highest and lowest quintiles. The authors found no associations between intakes of poultry, fish, dairy products, eggs, total fat, saturated fat, or cholesterol and pancreatic cancer risk. They suggest that because fat is not likely to contribute to the mechanism underlying the findings for meat consumption, carcinogenic substances resulting from meat preparation techniques might be responsible for the increase in pancreatic cancer risk.

3D MRI Useful in Detecting Most Lethal Cancers

Wed, 07 Sep 2005 07:46:38 PST

( from http://www.rxpgnews.com ) 3D MRI can detect pancreatic cancer when it is smaller and patients have a greater likelihood of survival, a new study shows.

The study included 57 patients who had clinical symptoms of pancreatic cancer. All had contrast enhanced 3D gradient-echo MRI examinations. Radiologists correctly identified pancreatic cancer in 24 patients, said Richard Semelka, MD, professor of radiology, at the University of North Carolina, Chapel Hill, and an author of the study. Eight of the cancers found were less than two centimeters in size, Dr. Semelka said. Currently patients with pancreatic cancer are treated with complete surgical resection and the smaller the tumor, the easier it is to remove, he said.

Pancreatic cancer is usually diagnosed too late, said Dr. Semelka. About 40,000 people are diagnosed with the disease in the U.S. each year, and nearly all of them die. Pancreatic cancer is the fourth most common cause of cancer death in the U.S. The symptoms of the disease are somewhat nonspecific and can easily be misinterpreted. In addition, the disease is very aggressive so if the disease is missed or the diagnosis is delayed, the patient's chance for survival is dismal, he said.

3D MRI did indicate pancreatic cancer in three patients, but biopsy showed they did not have the disease. However, one did have a neuroendocrine tumor and one had focal pancreatitis. Three patients were lost to follow-up, said Dr. Semelka. No patient with a study interpreted as normal was subsequently found to have pancreatic cancer, he added.

We are now working with our internists to detect this disease earlier, said Dr. Semelka. We are encouraging them to refer their patients for a 3D MRI examination if a patient has severe mid-abdominal pain not explained by a back problem, sudden development of diabetes and/or sudden development of jaundice. Radiologists who are reading 3D MR images of patients with abdominal pain should also look for pancreatic cancer even if the patient didn't have the examination for that purpose, he said.

New onset of hyperglycemic diabetes in adults age 50 or older - signal of underlying pancreatic cancer

Mon, 01 Aug 2005 16:59:38 PST

( from http://www.rxpgnews.com ) ROCHESTER, Minn. -- In a groundbreaking population-based study, researchers in Mayo Clinic Cancer Center found that new onset of hyperglycemic diabetes in adults age 50 or older may be a signal of underlying pancreatic cancer. The risk of developing the cancer within three years after a new diagnosis of diabetes is eight times higher than for the average same-age individual. The findings will be published in the Aug. 1 issue of Gastroenterology.
"Pancreatic cancer is difficult to detect until it is in an advanced stage, leaving little hope for patients," says Suresh Chari, M.D., Mayo Clinic gastroenterologist and lead investigator of the study. "This study is important, because it leads us closer to finding indicators that will allow earlier detection and treatment."

Pancreatic cancer is a deadly disease nearly all patients die that claims 32,000 lives in the United States each year and has an equal number of diagnoses annually. Patients with this type of cancer seldom exhibit disease-specific symptoms until the cancer is at an advanced stage, and two major obstacles prevent physicians from making an early diagnosis. First is the lack of a high-risk group a population of individuals, other than rare genetic disorders, in whom pancreatic cancer is common; and second is a lack of a PSA-like blood test for pancreatic cancer. Dr. Chari and his team's study shows that new-onset diabetes defines a high-risk group for pancreatic cancer.

While the study showed that about 1 percent of patients who met fairly stringent criteria for diabetes developed pancreatic cancer within three years, in most patients the cancer was at an advanced stage at diagnosis. Because patients in this study had not been screened for diabetes or pancreatic cancer, Dr. Chari's team was looking at those diagnosed after the fact. "Our goal now is to identify a marker in the blood that will enable us to distinguish diabetes associated with pancreatic cancer from the far more common type 2 diabetes," said Dr. Chari, "so we are able to screen patients with new-onset diabetes to detect pancreatic cancer before it spreads."

The study population of 2,122 patients was drawn from the Rochester Epidemiology Project and included all residents age 50 or older of Rochester, Minn., between 1950 and 1995. Comparison to the general populace was made using data from the Iowa Surveillance, Epidemiology and End Results (SEER) program.

Protein responsible for unchecked cell growth found

Sun, 12 Jun 2005 05:47:38 PST

( from http://www.rxpgnews.com ) Making new strides in their ongoing effort to understand mechanisms behind the relentless growth of cancer cells, researchers at Dartmouth Medical School have found a promising key that may open doors to future treatments in pancreatic and other forms of cancer. The innovation lies in manipulating an overabundance of chemo-resistant molecules in pancreatic cancer that inactivate pathways that would normally suppress cell growth.

Published in the June 10 issue of the Journal of Biological Chemistry, the study was led by Dr. Murray Korc, a pioneer in early research on growth factor receptors in pancreatic cancer, and chair of the department of medicine at Dartmouth Medical School (DMS) and Dartmouth-Hitchcock Medical Center, and a member of the Norris Cotton Cancer Center. His team's research has focused on suppressing pancreatic tumor growth by determining the mechanisms that enable the cells to grow so quickly.

"Pancreatic cancer is an incredibly resilient and aggressive disease," said Korc. "It grows quickly without causing symptoms, is resistant to chemotherapy, has a strong tendency to metastasize, and patients are often beyond surgery when it is diagnosed."

This study builds on the team's prior research on a molecule called Smad7, found in half of all human pancreatic cancers. Smad7 lies in pathways that normally play an important role in regulating cell growth and often prevents cells when proliferating too quickly. But Smad7 interferes with these pathways that are normally regulated by TGF-beta molecules, so they cannot regulate the growth of cells, and these cells continue to grow unchecked until they eventually become tumors.

"Previously, we found that Smad7 blocks the ability of TGF-beta to inhibit the growth of these cancer cells," said study co-author Dr. Nichole Boyer Arnold, a postdoctoral fellow at DMS and a member of the Norris Cotton Cancer Center. "In this study, we discovered that Smad7 is able to do this by suppressing the function of the retinoblastoma (RB) protein." The RB protein is crucial to empowering TGF-beta to control cell growth.

DMS researchers also found that pancreatic cancer cells generate TGF-Ò molecules at a much faster rate than normal. "It's a devilish mechanism," explains Korc. "Smad7 not only prevents TGF-beta molecules from slowing the cancer down, but enables them to multiply at a high rate, and thus gives the cancer another growth benefit. In addition, TGF-beta molecules are still able to stimulate blood vessel formation and enhance the growth of adjoining cells, which further increases the cancer's ability to metastasize."

Korc likens the process to a scorpion that not only has a newfound immunity to his own poison, but every time he stings himself, he gets bigger and more powerful.

"Now that we know how Smad7 is able to inactivate TGF-beta growth suppressive effects by preventing RB from functioning properly, we can focus our research on the RB protein," said Korc. They hope to find a way to disrupt Smad7's ability to affect the RB protein in human pancreatic cancers. Of the 31,000 people in the US that get pancreatic cancer this year, 30,300 will die from it, according to Korc, and most patients die within six months, which is why these advances in new therapies are so important.

He notes that even if his lab is able to overcome these problems in RB, it will not lead to a "cure" for pancreatic cancer. Pancreatic patients are under attack from so many different directions that the answer will not lie in one particular aspect of therapy. The authors hope that their work will add to a growing arsenal of treatments that, when combined in a form of therapy individualized to each patient, will have an impact on this devastating disease.

Disease progression model of pancreatic cancer developed

Sat, 21 May 2005 00:02:38 PST

( from http://www.rxpgnews.com ) Building on previous work, researchers at the University of Pennsylvania School of Medicine have developed an animal model of pancreatic cancer that closely mimics disease progression in humans. From this, they hope to develop new treatments for this deadly disease. Advanced pancreatic cancer is among the most lethal of cancers, with a one-year survival rate after chemotherapy of only 17 to 28 percent of patients, according to the National Cancer Institute.

Sunil R. Hingorani, MD, PhD, and David A. Tuveson, MD, PhD, both in the Departments of Medicine and Cancer Biology, and colleagues, engineered mice to express two mutant genes commonly associated with pancreatic cancer: Kras, an oncogene, and p53, a well-studied tumor suppressor. The investigators linked physiological, cellular, and genomic changes due to mutations in Kras and p53 in the mice to changes similar to that observed in pancreatic cancer patients. They report their findings in the May issue of Cancer Cell.

The disease that develops in the Kras and p53 mutant mouse model demonstrates distinct similarities to human pancreatic cancer at multiple levels. "In terms of clinical presentation, metastatic burden, and histological changes in tissue, this model appears to closely mimic the human disease," says Hingorani.

Clinical symptoms in the mutant mice mirrored those displayed in pancreatic cancer patients, such as abdominal swelling and muscle loss. Similarly, the progression of pancreatic cancer metastases paralleled that seen in the human disease. "In this model, pancreatic cancer metastasizes to the liver, lungs, diaphragm, and adrenal glands, all the same places that human pancreatic cancer metastasizes," says Tuveson.

The frequency of metastases to these various organ sites was also highly similar to that seen in humans. In human patients, 60 to 80 percent develop metastases to the liver; and 50 to 60 percent develop metastases to the lungs. In the genetically modified animals, 63 percent displayed liver metastases, and 45 percent displayed lung metastasesfurther emphasizing the accuracy of this model in mimicking human pancreatic cancer.

To understand the progression of pancreatic cancer, Hingorani and colleagues studied cell lines derived from primary tumor and metastasized cells. From this, the researchers established the occurrence of genomic instability in the mouse model. Genomic instabilitycontinuous formation of mutated chromosomesleads to widespread genetic changes throughout the affected cells. Genomic instability is seen in many human epithelial cancers, including pancreatic cancer, and is thought to be a driving force in the transition from local tumor growth to metastases of cancers. According to Hingorani, "This model may prove useful to understanding human pancreatic and other epithelial cancers because the key event of genomic instability that has been very difficult to model in the mouse appears to be recapitulated here."

In the pancreatic tumors and metastases from the mouse model, the investigators characterized other molecules implicated in pancreatic cancer. Often, the expression of molecules such as growth factors and their receptors will offer possible targets for treatment. The researchers were surprised to discover a high degree of heterogeneity in expression among these key molecules across the specimens. After ruling out the likelihood that this variability resulted from additional acquired mutations in known key tumor suppressor pathways, Hingorani suggests, "there may actually be unique genetic routes to pancreatic cancer, such that not all pancreatic cancers are equivalent."

The development of the first animal model for pancreatic cancer that fully imitates the progression of the human condition will likely open many new doors in understanding this debilitating disease. "With a model that can generate the full spectrum of disease, from preinvasive to invasive and metastastic lesions, we can begin to tease out the events that are linked to the progression of pancreatic cancer," explains Hingorani. "In trying to understand what events are required to create and support invasive and metastatic disease, we hope to translate our findings into better therapies," states Hingorani.

Processed Meats Linked to Pancreatic Cancer

Thu, 21 Apr 2005 17:48:38 PST

( from http://www.rxpgnews.com ) Heavy consumption of hot dogs, sausages and luncheon meats, along with other forms of processed meat, was associated with the greatest risk of pancreatic cancer in a large multiethnic study reported today at the 96th Annual Meeting of the American Association for Cancer Research.

The results suggest that carcinogenic substances related to meat preparation, rather than their inherent fat or cholesterol content, might be responsible for the association, said Ute Nöthlings, DrPH, MSE, the studys lead investigator from the Cancer Research Center at the University of Hawaii in Honolulu.

Meat consumption has been linked to pancreatic cancer in several case-control studies in the past, but the results have been inconsistent and data from prospective studies has been lacking.

For this study, researchers from the Cancer Research Center and USC examined the relationship of diet to pancreatic cancer among 190,545 men and women of African-American, Japanese-American, Caucasian, Latino and Native Hawaiian origin who were part of the Multiethnic Cohort Study in Hawaii and Los Angeles. An average follow-up of seven years yielded 482 incident cases of pancreatic cancer.

The researchers found that the heavy consumption of processed meats resulted in the highest risk for pancreatic cancer, after adjusting for age, smoking status, history of diabetes, familial history of pancreatic cancer and ethnicity. Those who consumed the greatest amount of processed meats had a 67 percent increase in risk over those participants with the lowest intake of this food category. A diet rich in pork and red meat also increased pancreatic cancer risk by about 50 percent, compared to their counterparts who ate less meat.

Consumption of poultry, fish, dairy products and eggs showed no link to pancreatic cancer risk, nor did overall intake of total fat, saturated fat, or cholesterol.

An analysis of fat and saturated fat intakes showed a significant increase in risk for fats from meat, but not from dairy products, indicating that fat and saturated fat are not likely to contribute to the underlying carcinogenic mechanism, said Nöthlings.

In particular, the scientists suggest that chemical reactions that occur during the preparation of processed meats might be responsible for the association. Such reactions can yield carcinogens including heterocyclic amines or polycyclic aromatic hydrocarbons.

Our study is the largest of its kind to demonstrate a link between high consumption of processed meats over long periods of time and pancreatic cancer, said Nöthlings. The sample size allowed us to obtain statistically significant risk-estimates that support this hypothesis.

No Association Between Dietary Patterns and Pancreatic Cancer

Wed, 06 Apr 2005 17:07:38 PST

( from http://www.rxpgnews.com ) Researchers from the Harvard School of Public Health (HSPH), assessing dietary patterns among men and women and risk of pancreatic cancer, found no association with two wide-ranging dietary patterns and the risk of pancreatic cancer.

Dominique Michaud, assistant professor of epidemiology at HSPH and lead author of the study and colleagues, assessed the dietary patterns of nearly 125,000 participants who were enrolled in the Brigham and Women's Hospital-based Nurses' Health Study (NHS) and the HSPH based Health Professionals Follow-up Study (HPFS). Analyzing detailed food frequency questionnaires sent to the participants every four years between 1984 (for NHS participants) and 1986 (for HPFS participants) and up to 2000, they identified two dietary patterns; the western diet, consisting of high consumption of red meat, processed meat, French fries, processed grains, sweets, desserts and sugared beverages and the prudent diet, consisting of high consumption of fruits, vegetables, fish, poultry, legumes and whole grains. During the span of the study 366 cases of pancreatic cancer were documented (185 men and 181 women).

The researchers found no strong association between the two dietary patterns and the risk of pancreatic cancer among the study participants, even when looking at lifestyle factors such as smoking and body mass index. Participants who were the strongest adherents to the prudent diet also had healthier lifestyle behaviors, such as not smoking, exercising more, taking multivitamins and drinking less alcohol compared to the participants in the study who were the strongest adherents of the western diet.

Although we did not find any associations with two major dietary patterns, individual dietary components are still likely to play a role in the risk of pancreatic cancer, said Dominique Michaud. We have previously shown that a high glycemic load and dietary sugar are related to an elevated risk of pancreatic cancer among women. More research needs to be done to examine individual dietary factors. Prevention is a priority in such a highly fatal disease. Both smoking and obesity increase pancreatic cancer risk and should be considered for prevention.