Targeted Gene Therapy May Offer Hope Against Melanoma

A new targeted gene therapy for advanced skin cancer is effective in majority.

Aug. 26, 2010— -- Gene targeting drug therapy may offer hope for those with difficult-to-treat advanced-stage skin cancer according to preliminary data published Wednesday in the New England Journal of Medicine.

While skin cancer is highly treatable when caught early, once it spreads to other parts of the body (metastasizes), current treatments are limited and are effective in only a fraction of patients. The chance of survival for patients with metastatic melanoma is usually nine months or less.

The new treatment targets a mutation of the protein BRAF, which causes it to become overactive and cancer-producing in over half of all melanomas. Treatment with the drug was able to shrink tumors and slow the progression of the disease for 81 percent of patients who carry that mutation.

"This type of treatment gets to the root of what caused the cancer," says lead author Dr. Keith Flaherty, and provides hope for patients who until now had few, if any effective treatment options. Flaherty is director of Developmental Therapeutics at the Massachusetts General Hospital Cancer Center

Though it is too early to tell what effect this treatment could have on the life expectancy of such patients, doctors are calling this drug a potentially life-saving breakthrough.

"This therapy results in dramatic responses for patients -- it's phenomenal. I've been taking care of patients with advanced melanoma for 25 years and this is one of the most important breakthroughs we've seen," says Dr. Lynn Schuchter, professor of medicine at the Abramson Cancer Center at the University of Pennsylvania. She administered this drug as part of the drug trials.

How Gene Targeting Works

There are currently only two FDA-approved drugs for metastatic melanoma: interleukin-2 and dacarbazine, both of which provide limited results at best.

Interleukin-2 works in very few cases and dacarbazine, a form of chemotherapy, has not been shown to improve survival, notes Dr. Kelly McMasters, professor of medicine at the University of Louisville Department of Surgery.

Genetically targeted treatment, however, attacks the problem in an entirely different way. Instead of acting broadly on the immune system or cell growth, scientists identify the specific genetic mutation that may have caused the cancer in the first place and find a way to suppress the actions of that mutation.

BRAF, the protein affected by Flaherty's treatment, is pathologically overactive in 8 percent of cancers and over half of all melanomas so the treatment works by blocking this overactivity.

Preliminary Data Promising

The treatment is in the form of a pill and has limited negative side effects, including skin rash and the formation of new, non-cancerous lesions.

Schuchter says that patients tolerated the treatment well and even reported that the pain associated with their condition was significantly reduced within 24 hours of starting the medication.

Only those patients that have the BRAF mutation are able to benefit from this treatment however, and a majority, but not all of patients with the mutation see results.

Another drawback is that the drug tends to lose its effectiveness.

"Ultimately, resistance to the drug develops. It's the same idea as when bacteria develop a resistance to certain antibiotics, the same thing can happen with cancer and cancer therapy," says Schuchter.

So far, the research shows an average progression-free survival in patients of about eight months. Though the results of the therapy don't seem to be permanent, it buys time to strategize second-line therapies and figure out how to prevent this resistance, says Flaherty.

Phase II trails have been conducted for this drug and a head-to-head phase III trial between the drug and dacarbazine is in the works, he adds.

Given the lack of effective melanoma treatments, he hopes this drug will get FDA approval based on the results from the current phase II trail and made available to patients by next summer.

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