RxPG News : Renal Cell Carcinoma

Tailor made approach to kidney cancer

Sat, 01 Nov 2008 03:39:36 PST

( from http://www.rxpgnews.com ) A study of nearly 1,500 patients treated for kidney cancer at UCLA in the last 15 years shows that an aggressive, tailored treatment approach results in better survival rates and uncovered subsets of kidney cancer that behave differently and need to be treated accordingly.

The one-size-fits-all approach traditionally used in kidney cancer treatment should be changed based on the results of the study, the longest to date to analyze kidney cancer patients and their outcomes, said Dr. Arie Belldegrun, senior author of the study, a professor of urology and a researcher at UCLA's Jonsson Comprehensive Cancer Center.

"This is the most important work that we've done out of the kidney cancer program at UCLA," Belldegrun said. "We outline the foundation for personalized kidney cancer therapy. We have shown that not all kidney cancer patients are the same, not all localized kidney cancers are the same and not all metastatic kidney cancers are the same."

The study appears in the Nov. 1, 2008 issue of Cancer, the peer-reviewed journal of the American Cancer Society.

The study found that patients with localized kidney cancer, cancer that has not spread to other organs, could have either low, intermediate or high risk cancers based on the chance for recurrence. Patients with cancers that have already spread also fell into similarly different subsets. Some have better outcomes while others may have very aggressive cancers that may not warrant treatment.

"We showed for the first time, using an integrated staging system developed at UCLA, that we can identify which patients with localized disease fall into the low, intermediate and high risk subsets and which patients with metastasized cancers are either low, intermediate or high risk patients," Belldegrun said. "Now we can make treatment decisions based on that."

If a patient with localized cancer is identified as low risk, his five-year survival rate is expected to be 97 percent, while his 10-year survival rate is 92 percent. An intermediate risk patient with localized disease would have a five-year survival rate of 81 percent and a 10-year survival rate of 61 percent. A high risk patient has a five-year survival rate of 62 percent, with a 10-year survival of 41 percent.

"All of these patients with cancers that have not spread present to their doctors with presumably localized disease and in the past they may have been treated the same way," Belldegrun said. "They need to be treated individually according to their risk levels."

The study showed that a patient with low-risk, localized kidney cancer could be treated only with surgery and expect an excellent outcome. Such a move would spare the patient from having to undergo radiation or immunotherapy, which result in harsh side effects. However, for a patient with high-risk, localized kidney cancer, surgery would not be enough. Additional therapy such as targeted treatments or immunotherapy should be considered in order to give the patient the best possible outcome.

In metastatic patients, someone with low-risk cancer should get very aggressive treatment, Belldegrun said, because there's a good chance the therapy will help the patient. Those with high-risk, metastatic disease won't get much, if any, benefit from treatment and may want to forego surgery and the toxic therapies.

"Our paper identifies, very precisely, which patients should get which therapies," Belldegrun said.

The study represents 15 years of experience in UCLA's leading-edge kidney cancer program, an interdisciplinary approach to treating cancer that brings together medical oncologists, urologists, surgeons, clinical trials experts and scientists under one roof, a concept that was first conceptualized at UCLA. The study analyzed the first 1,492 patients treated in the program and "demonstrated that outstanding results can be achieved using this approach," Belldegrun said.

About 25 percent of the patients with metastatic kidney cancer achieved long-term responses – five to 15 year survivals – from their therapy, Belldegrun said. Less than 5 percent of metastatic kidney cancer patient typically achieve long term survivals or a cure when treated with conventional treatments.

"This is by far the best survival data in such a difficult group of patients," Belldegrun said. "This can be achieved today only in kidney cancer centers of excellence like we are operating at UCLA, where we have all the expertise at hand, the best scientists, clinicians and surgeons working together."

The results of the study come as new targeted therapies are being introduced specifically for kidney cancer. The U.S. Food & Drug Administration has recently approved three such drugs. Belldegrun said the survival rates detailed in their paper should be used as a benchmark to which these new therapies should be compared.

"While the field of kidney cancer is undergoing dramatic changes it is as yet still unclear how these changes are affecting patient outcome," the study states. "A critical assessment of the potential improvement in the new treatment era necessitates a comparison to a known benchmark. We present long-term, single institution data to provide a thorough understanding of the results that have been achieved until now using a consistent, aggressive approach for localized and metastatic disease. For future patient care, it will be important to select patients that will do best using existing therapies, and those who should be treated using the newly approved treatments."

Temsirolimus is effective for advanced renal cell carcinoma

Fri, 01 Jun 2007 03:59:37 PST

( from http://www.rxpgnews.com ) The results of a phase III, randomized clinical study involving patients with advanced renal cell carcinoma and poor prognostic features show temsirolimus improved overall survival when compared to the current treatment for this stage of disease. The study, led by Gary R. Hudes, M.D., director of the Genitourinary Malignancies Program at Fox Chase Cancer Center, is published in the May 31 issue of the New England Journal of Medicine.

A total of 626 patients with renal cell carcinoma (RCC) were enrolled in the study and received one of three treatments ? a new drug called temsirolimus, an older drug called interferon, or both the new and old drugs together. The patients who received temsirolimus alone survived longer than those who received interferon, the usual or ?standard? treatment for this disease.

This is the first study to show that a new drug can improve overall survival for patients with metastatic renal cell cancer, said Hudes.

Patients who received both drugs - temsirolimus and interferon - did not appear to live longer than those given interferon. Hudes said this finding could be explained by the lower dose of temsirolimus given to patients who received the combination treatment.

Renal cell carcinoma (RCC) is the most common type of kidney cancer. Approximately 90 percent of the 51,190 new cases of kidney cancer diagnosed this year will be RCC. Although many patients with kidney cancer are cured by surgery that removes the tumor, approximately 35 percent of patients will experience a recurrence of their cancer or will have spread (metastasis) of their cancer to other organs.

For these patients, the goal of treatment is to prevent further spread and growth of the cancer, and ideally, to reduce that amount of cancer, Hudes said. Until recently, physicians lacked effective drugs to control the disease.

In the current study, the greatest increase in median survival was observed in patients randomized to receive temsirolimus (49 percent) compared with patients treated with interferon only. Patients treated with temsirolimus and interferon combined had a 15 percent increase in median survival compared with interferon alone. The median survival for temsirolimus alone was 10.9 months compared with and 8.4 months for the temsirolimus and interferon, and 7.3 months for the interferon.

This is a modest improvement in survival but the patients in the study had the most advanced tumors, says Hudes. It would be reasonable to hypothesize that temsirolimus could provide greater benefit to patients with less extensive metastatic disease. Only a randomized, clinical trial will give us that definitive knowledge.

Temsirolimus was better tolerated than interferon. Fewer patients treated with temsirolimus had grade 3 or 4 (severe) side effects compared with those treated with interferon or the combination of interferon and temsirolimus. Asthenia, anemia, nausea, dyspnea, and rash were the most common side effects associated with temsirolimus.

Temsirolimus (formerly known as CCI-779) blocks the function of the mammalian target of rapamycin (mTOR), a key protein within cells that regulates cell proliferation, growth and survival. Temsirolimus may also block angiogenesis, a process that tumors use to create a blood supply to maintain their growth.

In November 2006, Wyeth filed an application with the U.S. Food and Drug Administration for approval to market temsirolimus (brand name Torisel) for the treatment of advanced renal cell carcinoma. A decision on approval is expected before July 2007.

Renal cancer related to deficiency in exposure to sunlight

Tue, 19 Sep 2006 14:52:37 PST

( from http://www.rxpgnews.com ) Using newly available data on worldwide cancer incidence to map cancer rates in relation to proximity to the equator, researchers at the Moores Cancer Center at University of California, San Diego (UCSD) have shown a clear association between deficiency in exposure to sunlight, specifically ultraviolet B (UVB), and kidney cancer.

UVB exposure triggers photosynthesis of vitamin D3 in the body. This form of vitamin D also is available through diet and supplements. Previous studies from this core research team have shown an association between higher levels of vitamin D3 and a lower risk of cancers of the breast, colon and ovary.

"Kidney cancer is a mysterious cancer for which no widely accepted cause or means of prevention exists, so we wanted to build on research by one of the co-authors, William Grant, and see if it might be related to deficiency of vitamin D," said study co-author Cedric Garland, Dr. P.H., professor of Family and Preventive Medicine in the UCSD School of Medicine, and member of the Moores UCSD Cancer Center.

There will be approximately 208,500 cases and 101,900 deaths from kidney cancer worldwide in 2006, including 39,000 new cases and 12,700 deaths in the United States, according to the International Agency for Research on Cancer and the American Cancer Society.

The study, published in the International Journal of Cancer's online edition dated September 15, is the research team's newest finding relating exposure to the sun as a source of vitamin D, and estimated vitamin D deficiency to higher rates of several major types of cancer.

This paper used worldwide data only recently available through a new tool called GLOBOCAN, developed by the World Health Organization's International Agency for Research on Cancer. GLOBOCAN is a database of cancer incidence, mortality and prevalence for 175 countries.

The researchers created a graph with a vertical axis for renal cancer incidence rates, and a horizontal axis for latitude. The latitudes range from -90 for the southern hemisphere, to zero for the equator, to +90 for the northern hemisphere. They then plotted incidence rates for 175 countries according to latitude. The resulting chart was a parabolic curve that looks like a smile (see accompanying images).

"The plot points created a curve roughly resembling a smile, with countries with high incidence rates at the left and right, and those with low incidence rates in the center, just a few degrees from the equator," said Garland. "Countries with the highest cancer rates were places like New Zealand and Uruguay in the southern hemisphere and Iceland and the Czech Republic in the northern hemisphere. Clustered at the bottom of the curve with lowest incidence rates were Guam, Indonesia and other equatorial countries on most continents, including many varied equatorial cultures."

In addition to UVB, the researchers analyzed cloud cover and intake of calories from animal sources for their association to kidney cancer. The scientists were able to determine the contributions of each independently. After accounting for cloud cover and intake of animal protein, UVB exposure still showed a significant independent association with incidence rates.

"Because the distinctive "smiley" parabolic curve is present for both sexes, it is unlikely that the international differences are due to occupational exposures, which usually vary according to gender, " said co-author Sharif B. Mohr, M.P.H.

In the paper, the authors discuss and account for other possible variables such as ozone, aerosols and obesity.

"This was a study of aggregates, or countries, rather than individuals. Findings that apply to aggregates may not apply to individuals," said co-author Edward D. Gorham, M.P.H., Ph.D.

"Since ecological studies may not be able to control for all relevant confounding factors, observational studies of the effect of vitamin D from sunlight, diet and supplements on the risk of kidney cancer in individuals would be desirable," Gorham added.

Sunitinib malate more effective than standard cytokine treatment in metastatic renal cell carcinoma (mRCC)

Mon, 05 Jun 2006 16:33:37 PST

( from http://www.rxpgnews.com ) According to a new study, the drug sunitinib malate is more effective than the current standard cytokine treatment given as an initial therapy for patients with advanced kidney cancer, also known as metastatic renal cell carcinoma (mRCC).

"This drug has shown more activity as a single agent against advanced kidney cancer than any other drug I've studied in the past 15 years," said the study's lead author Robert J. Motzer, MD, a medical oncologist at Memorial Sloan-Kettering Cancer Center (MSKCC). "I continue to be encouraged by its effectiveness in treating patients with this aggressive disease," said Dr. Motzer, who is a leader in the treatment of kidney cancer and conducted the earliest clinical trials on sunitinib (initially referred to as SU11248).

Interferon-alpha (IFN-Ü) is one of the standard treatments for advanced kidney cancer, however only about 15 percent of patients respond to this immunotherapy. Sunitinib targets receptors on kidney cancer cells that may play a role in tumor growth and the development of blood vessels that feed a tumor. Previous clinical trials, also led by Dr. Motzer, showed that sunitinib caused some renal cell cancers to shrink, but this study is the first to demonstrate its effectiveness as a first-line therapy compared with standard cytokine therapy with IFN-Ü.

The current randomized trial included 750 patients over the age of 60, half of whom were treated with a six-week cycle of sunitinib and half of whom were treated with a six-week cycle of the current treatment standard, IFN-Ü. The primary endpoint of the trial was a comparison of progression-free survival between sunitinib and IFN-Ü as assessed by independent third-party review. The median progression-free survival for treatment with sunitinib was 11 months, compared with 5 months following treatment with IFN-Ü. This outcome was statistically significant and met the primary question asked by investigators in the trial. In addition, 31 percent of the patients in the sunitinib arm of the study experienced substantial tumor shrinkage compared with 6 percent of the patients receiving the standard treatment.

"This drug offers new hope for the initial treatment of patients battling metastatic kidney cancer, which is otherwise resistant to chemotherapy," said Dr. Motzer.

Bayer wins positive response for cancer drug

Sun, 30 Apr 2006 19:24:37 PST

( from http://www.rxpgnews.com ) Bayer AG said Friday that the company and its US partner Onyx Pharmaceuticals Inc have received a positive response from European officials to their drug to treat kidney cancer.

The opinion of the European Committee for Medicinal Products for Human Use (CHMP) of the drug Nexavar would now be passed onto the European Commission.

A positive ruling by the commission could pave the way for a marketing authorisation for all EU nations in the second half of this year.

The announcement coincided with Bayer's annual general meeting in Cologne, where the group's chief Werner Wenning sought to secure shareholders' support for the planned 16.5 billion euros ($21 billion) takeover of rival pharmaceuticals firm Schering AG.

Describing the proposed acquisition as a milestone in the company's history, Wenning said that this move was the "right step" for the group.

The takeover, Wenning said, would propel Bayer into "the top league of pharmaceutical makers around the world".

Wenning went on to tell the company's shareholders that the acquisition would result in the health services section emerging as the key engine for growth.

Bayer's 86-euro a share offer for Berlin based Schering runs until the end of May with the takeover representing the biggest acquisition in Bayer's corporate history.

Imatinib mesylate is not likely to be effective for patients with high grade renal cell carcinoma

Thu, 22 Dec 2005 05:03:38 PST

( from http://www.rxpgnews.com ) Mayo Clinic Cancer Center investigators report that imatinib mesylate (GleevecTM), the drug used to treat patients with gastrointestinal stromal cancers (GISTs), is not likely to be effective for patients with high grade renal cell carcinoma -- the most aggressive kidney cancer. Results of the study are published in the January issue of The Journal of Urology.

"While this finding does not seem like good news for patients with kidney cancer," says Bradley Leibovich, M.D., Mayo Clinic urologist and lead investigator of the study, "it does help us to narrow down the treatment options among the new targeted therapy drugs and would seem to indicate that resources for investigating potential new kidney cancer therapies may be better utilized on other options."

The American Cancer Society reports that kidney cancer is diagnosed in over 36,000 people in the United States each year and kills more than 12,000 annually. Mayo researchers are looking for better ways to treat this and other cancers, and to alleviate the uncertainty that accompanies a cancer diagnosis by finding better ways to individualize treatment plans.

This study's purpose was to determine the frequency of KIT (a receptor kinase tyrosine) expression and mutation in aggressive kidney tumors. The goal was to be able to recommend imatinib as a viable treatment option for patients who may not be adequately treated by surgery alone. KIT is a cell-surface molecule involved in the production of blood cells, pigmentation and gametes (male and female sex cells). Mutations of KIT have been linked to several types of cancer, and KIT expression is often measured as an indicator of certain cancers. KIT expression also appears to be related to the effectiveness of imatinib for treatment of patients with GISTs, as reported in The New England Journal of Medicine in 2002.

KIT is expressed normally in kidneys and also frequently in oncocytomas and chromophobe kidney tumors, which are usually effectively cured by surgery -- not requiring additional therapy. Wanting to verify results found a 2004 study published in The Journal of Clinical Pathology, and another the same year in The Journal of Urology that reported frequent KIT expression in these tumor types, Dr. Leibovich's team investigated sarcomatoid and high-grade kidney tumors. Since these tumors are aggressive and may recur after surgical removal, treatment after surgery with new targeted drug therapies would potentially benefit patients.

Using positive immunohistochemical staining, the researchers found no evidence to support those previous findings and reported only about 4.5 percent of the tumors showed KIT expression. "Imatinib only would have had the potential to be helpful to that small percentage of patients that we found to have a KIT-positive tumor," says primary author Shomik Sengupta, M.D. "And even then it would only work if they also had specific mutations that would respond to the drug."

Drs. Leibovich and Sengupta and their fellow researchers believe the misconception that mere detection of KIT predicts tumor responsiveness was born of the successful treatment of GISTs with imatinib. They say that it is not simply KIT expression, but rather cancerous KIT mutations that result in the GISTs success as well as the failures in other tumors. "Tumors that express KIT but lack KIT mutations may not respond to imatinib, and other researchers have shown that recently for adenoid and small cell lung cancers," says Dr. Leibovich. "Because we rarely found KIT expression and no KIT mutations, we cannot justify imatinib therapy." They also cited differences in staining protocols as reasons the other studies obtained different results.

This study reviewed records of all patients undergoing partial or radical nephrectomy between 1970 and 2002. The records were obtained from the Mayo Clinic Nephrectomy Registry, which includes over 5,000 patients. A total of 194 patients with nuclear grade 4 (highly aggressive) tumors were part of the final study analysis. An additional 50 had been identified, but insufficient tissue was available for analysis.