Study shows combination improves survival of metastatic melanoma patients

Two chemotherapy drugs combined with an agent that prevents the growth of blood vessels significantly delayed the spread of tumors in patients with metastatic melanoma, according to study findings presented at the 2007 American Association of Clinical Oncology (ASCO) Annual Meeting.

In this phase II clinical trial of 53 patients, tumor growth was delayed by almost six months, whereas, typically, these cancers begin spreading again eight weeks after chemotherapy treatment, researchers say.

The researchers from Mayo Clinic and the North Central Cancer Treatment Group (NCCTG), caution that while the findings are promising, they are preliminary.

"This is the most effective treatment we have ever tested at Mayo Clinic for this type of cancer, but the results need to be validated," says Svetomir Markovic, M.D., Ph.D., a Mayo Clinic oncologist and the study's principal investigator. "It is important for the public to know there is hope for patients with melanoma."

The study was presented today by Domingo Perez, M.D., the lead author of the study who is a former oncology fellow at Mayo Clinic and is now in private practice in Minneapolis.

"The clinical benefit may seem small, but in the world of melanoma where there is very little progress, this is certainly a strong indication that the combination of chemotherapy with an antiangiogenic agent may be a valid treatment strategy for these patients. But the only way to know this for certain is a head to head comparison with the standard course of treatment," Dr. Perez says.

Melanoma that has metastasized (spread) to other parts of the body is one of the most difficult cancers to treat. Though rare, it is also the most deadliest of skin cancers because it does not respond well to chemotherapy. About one melanoma patient dies every hour (8,000 every year) in the United States, and 60,000 new cases are diagnosed annually, Dr. Markovic says.

People who have been diagnosed with metastatic melanoma generally live between six and 12 months after diagnosis. Despite years of research, there are no long-term effective treatments and no cure.

In this study, researchers combined two chemotherapy drugs - paclitaxel (Taxol) and carboplatin - with bevacizumab, a drug that prevents the formation of new blood vessels and is used to treat cancer in combination with chemotherapy drugs.

The combination of paclitaxel (Taxol) and carboplatin has been beneficial in treating different cancers, such as metastatic lung cancer and ovarian cancer, Dr. Perez says.

Bevacizumab blocks the vascular endothelial growth factor (VEGF), a substance naturally produced in the body that stimulates the formation of new blood vessels, a process known as angiogenesis. This process is essential for tissue repair, such as wound healing, and for the overall the health of the body.

VEGF is also important for tumor growth, which depends to a large extent on the formation of new blood vessels to satisfy the increasing oxygen and nutritional needs of the growing tumor. Furthermore, there is evidence that overproduction of VEGF in response to chemotherapy may allow tumors to become more aggressive and resistant to the effects of chemotherapy by different mechanisms. Thus, it was thought that blocking VEGF with a drug like bevacizumab could facilitate the antitumor effects of chemotherapy in patients with metastatic melanoma.

Bevacizumab is a monoclonal antibody that binds VEGF and blocks its interaction with cellular receptors. This action prevents new blood vessels from forming and allows the chemotherapy to work.

Fifty-three patients were treated with carboplatin, weekly treatments of paclitaxel (Taxol) and biweekly bevacizumab. Researchers found that the treatment was well tolerated and prevented the tumor from spreading from eight to nearly 24 weeks.

The number of new melanoma cases has continued to rise at a rate of about 5 percent to 10 percent each year since the 1970s, Dr. Markovic says. Why" One cause, he says, is depletion of the ozone layer, but also, more cases are coming to light due to greater public awareness.

"The increase in incidence is a big worry, particularly when we still do not have an effective treatment. That's why this step, however small, is important," Dr. Markovic says.

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