foodconsumer.org: Fighting Back: New Drug for Melanoma Fighting Back: New Drug for Melanoma ================================================================================ Laura King on 08/26/2010 18:33:00 Fighting Back: New Drug for Metastatic Melanoma Melanoma is the most serious type of cancer of the skin. The National Cancer Institute (NCI) estimates more than 68,000 people will be newly diagnosed and almost 9,000 will die from melanoma this year. Melanoma has become increasingly more common every year. In the last 30 years, the percentage of people who develop melanoma has more than doubled. The NCI describes Melanoma: "a form of cancer that begins in melanocytes (cells that make the pigment melanin). It may begin in a mole (skin melanoma), but can also begin in other pigmented tissues, such as in the eye or in the intestines." When diagnosed early, melanoma can be successfully treated with chemotherapy or surgery. However, once it metastasizes to other areas of the body, chemotherapy is limited to Decarbazine and Interleukin-2, the only two drugs currently approved by the FDA for metastatic melanoma. The prognosis for patients diagnosed with metastatic melanoma is grim, most surviving nine months or less, as these two drugs are not effective with the majority of patients. In a study, led by Keith T. Flaherty, MD, Director of Developmental Therapeutics, Cancer Center, Massachusetts General Hospital and former University of Pennsylvania Oncologist, a genetically targeted drug has been discovered that shrank tumors in 80% of patients with metastatic melanoma. Based on "the identification of somatic mutations in the gene encoding the serine–threonine protein kinase B-RAF (BRAF) in the majority of melanomas offers an opportunity to test oncogene-targeted therapy for this disease" researchers reported in the New England Journal of Medicine this week, revealing that 40-60% of melanoma patients have this BRAF gene mutation, as well as 8% of all cancers. "This type of treatment gets to the root of what caused the cancer," says Flaherty, "and provides hope for patients who until now had few, if any effective treatment options." "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, Abramson Cancer Center, University of Pennsylvania, who administered this drug as part of the drug trials. Earlier this summer, researchers reported that ipilimumab, an immune-stimulating drug being developed by Bristol-Myers Squibb and Medarex Inc., extended survival for patients whose melanoma had metastasized from the skin to internal organs, making this the second breakthrough against a disease for which there had been no advancement in treatment for 20 years. The drug called PLX4032, developed by Plexxikon Inc., and Roche Pharmaceuticals, targets BRAF, a pathalogically overactive mutated protein blocking the mutation. With limited side-effects, the pill form was well tolerated in patients and pain was significantly reduced within 24 hours of starting the medication. Skeptics doubted that the BRAF gene was a good target for melanoma, due to the complexities of the disease that switches molecular signals and pathways making treatment difficult. Flaherty acknowledges that focusing on BRAF was a gamble following the realization that Nexavar an anti-BRAF drug approved to treat kidney cancer was not successful against melanoma. "It was scary and disappointing," recalled Flaherty, when the first group of patients did not respond to PLX4032, even at high doses. After interrupting the study and reformulating PLX4032 to make it easier for patients to absorb, results quickly turned around and success was realized. "I have never seen a drug response like this," said Schuchter. To ensure the drug was hitting the designated target, 39 of the first group of 55 patients did not have the BRAF gene mutation. Cancer continued to progress in all of the 39 non-BRAF patients. The second group of 32 patients, all with the BRAF mutation revealed an 81% success rate, shrinking tumors in 24 and complete disappearance in 2 patients. "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. A larger study, currently in process, will determine if these results will provide a longer overall survival period. Sixteen patients are continuing to benefit from ongoing therapy. An average progression-free survival thus far has shown to be about eight months, additional time to strategize and determine how to prevent resistance. Hoping to get FDA approval based on Phase II trials and the lack of melanoma treatments, Faherty suggests that perhaps the drug will be available by next summer. Melanoma patients are not the only ones who stand to benefit from the BRAF breakthrough. "The hope is that this is a bigger foot in the door for cancer therapy because of the prevalence of BRAF mutations," Flaherty said. ABC's of Melanoma - signs and symptoms - new or existing mole or skin lesion A - Asymmetry—The shape of one half does not match the other. B - Border—The edges are often ragged, notched, blurred, or irregular in outline; the pigment may spread into the surrounding skin C - Color—The color is uneven. Shades of black, brown, and tan may be present. Areas of white, grey, red, pink, or blue also may be seen. D - Diameter—There is a change in size, usually an increase. Melanomas are usually larger than the eraser of a pencil (1/4 inch or 5 millimeters). (pictures of the above are available on the NCI website) Skin self-exam is important in finding skin growths that may be melanoma. Melanomas usually do not cause pain and can hide in places like your scalp where they are covered by hair which makes a skin examination by a health care professional an important part of routine checkups. Some risk factors cited on the NCI website are: a high number of moles (more than 50); fair skin, family history of melanoma; weakened immune system; severe, blistering sunburns and Ultraviolet (UV) radiation including artificual UV radiation sources such as sunlamps and tanning beds. Prevention is always better than having to find the cure. Doctors recommend the following steps to help prevent and reduce the risk of melanoma caused by UV radiation: * Avoid exposure to the midday sun (from 10 a.m. to 4 p.m.) whenever possible. When your shadow is shorter than you are, remember to protect yourself from the sun. * If you must be outside, wear long sleeves, long pants, and a hat with a wide brim. * Protect yourself from UV radiation that can penetrate light clothing, windshields, and windows. * Protect yourself from UV radiation reflected by sand, water, snow, and ice. * Help protect your skin by using a lotion, cream, or gel that contains sunscreen. Many doctors believe sunscreens may help prevent melanoma, especially sunscreens that reflect, absorb, and/or scatter both types of ultraviolet radiation. These sunscreen products will be labeled with “broad-spectrum coverage.” Sunscreens are rated in strength according to a sun protection factor(SPF). The higher the SPF, the more sunburn protection is provided. Sunscreens with an SPF value of 2 to 11 provide minimal protection against sunburns. Sunscreens with an SPF of 12 to 29 provide moderate protection. Those with an SPF of 30 or higher provide the most protection against sunburn. *Wear sunglasses that have UV-absorbing lenses. The label should specify that the lenses block at least 99 percent of UVA and UVB radiation. Sunglasses can protect both the eyes and the skin around the eyes.