Skin cancer is the most common form of cancer with more than 600,000 new cases diagnosed each year with basal cell and squamous cell being the most common. The third type, melanoma, is more rare but is the most aggressive. According to the American Cancer Society, there were more than 68,000 new cases of melanoma reported in 2009. The incidences of melanoma have increased over the last 30 years. For those using indoor tanning methods, the chances of developing this disease are further increased.
The National Cancer Institute defines a number of risk factors for developing melanoma, including: Unusual moles; excessive exposure to natural sunlight or artificial ultraviolet light; family or personal history of the disease; having a fair complexion; and being older than 20 years of age.
Although surgery is the most effective way to treat melanoma, many patients present with advanced or metastatic disease. Newer options for these patients include the use of immunological therapies like interferon, interleukin-2 and, more recently, the anti-CTL4 antibody, as well as Ipilimumab. In select cases, Imatinib has also shown efficacy. Newer classes of agents that target the Braf gene are also in development.
Chemotherapy does not always work as well for melanoma as it does for some other types of cancer, but it may relieve symptoms or help people with advanced disease live longer. Several drugs and combinations of drugs can be used to treat advanced melanoma.
The most commonly used chemotherapies for the disease are dacarbazine used either alone or in combination with other chemotherapy drugs such as carmustine and cisplatin. The combination of these three drugs, together with tamoxifen is called the "Dartmouth regimen." Temozolomide works similarly to dacarbazine, but it can be given in pill form. Paclitaxel is administered either alone or combined with drugs such as cisplatin or carboplatin. Additional drugs with activity include alkylating agents (Melphalan), vinca alkaloids (Vinblastine) and Bleomycin.
The graph below is excerpted from a clinical trial that compared empiric chemotherapy with assay-directed chemotherapy in patients with advanced melanoma. The data illustrates a statistically significant survival advantage for patients receiving assay-directed therapy. Despite melanoma’s drug refractory nature, novel drug combinations have the potential to provide durable responses in some patients.
Invitro Drug Sensitivity Predicts Response and Survival after Individualized Sensitivity-Directed Chemotherapy in Metastatic Melanoma: AMulticenter Phase II Trial of the Dermatologic Cooperative Oncology Group