There are a number of agents that have been reported to have activity in therapy of malignant melanoma. All are relatively well tolerated and have response rates of 15 to 20%.
- Dacarbazine (DTIC) is the only chemotherapy treatment for melanoma approved by the Food and Drug Administration and the most commonly prescribed. It is typically administered intravenously. Studies have shown dacarbazine causes tumor shrinkage in 15-20% of patients for an average of six months before the tumor resumes growth. To date, dacarbazine has not been shown to significantly prolong overall survival.
- Carmustine (BCNU) is a drug that belongs to a group of drugs known as nitrosoureas
- Iomustine (CCNU) Cisplatin is one group of drugs known as alkylating agents
- Temozolomide (brand name Temodar) is an oral drug for the treatment of advanced metastatic melanoma. Clinical trials have shown Temozolomide is as effective as dacarbazine and easier to administer with fewer side effects
In an attempt to improve the therapeutic outcome in patients with metastatic melanoma, a number of combination regimens have been tried. The most widely used of these is known as the "Dartmouth Regimen" and consists of quadruple drug therapy with DTIC, Cisplatin, BCNU and tamoxifen. In a large randomized trial that included 240 patients, it was reported that the combination chemotherapy regimen described above as the "Dartmouth Regimen" was no better than therapy with a single agent DTIC in terms of tumor response or survival.
Alpha interferon has direct activity in inhibiting the growth of melanoma cells and also has immunological effects. The response rate in melanoma is 15-20%.
Interleukin-2 (IL-2) has been extensively studied over the past several years at many centers and is approved by the Federal Drug Administration for therapy in patients with metastatic melanoma. Use of IL-2 offers the potential for a durable response in a small percentage of patients. Responses are strongly associated with the site of metastasis showing a significantly higher response rate than patients with metastases to other sites.
Tumor vaccines are being widely used as adjuvant therapy of melanoma. Vaccines have potential for preventing recurrence and prolonging survival when a patient has been rendered clinically tumor-free by standard means, such as surgery, but is known to be at high risk for recurrence. Preliminary results in this circumstance have been promising, but definitive studies have not yet been completed.
Because of these promising results in patients clinically tumor-free, and the low toxicity of vaccines, patients with metastatic disease are also seeking vaccine treatment. It must be recognized that the circumstances in the therapy of metastatic disease are different from adjuvant therapy. With adjuvant therapy, the tumor burden is minimal and there is potential for the immune response to overcome this minimal tumor burden. In patients with demonstrated metastases which cannot be treated with surgery or other standard means, the tumor burden is much greater and it is too much to expect successful therapy in a large percentage of patients with vaccines currently available. It is simply asking too much of the immune response to be able to overcome a substantial tumor burden. The response rate to tumor vaccines in patients with metastatic disease is in the range of 10-20%.
Because chemotherapeutic and biologic agents have activity in therapy of melanoma, combinations have been tried in an effort to provide clinical benefit to patients in terms of improved responses and longer survival.
Recently, a number of new agents have entered clinical trials. Once of the most promising is a monoclonal antibody called anti-CTLA-4. This antibody had the effects of "taking the brakes off" the immune system thereby causing enhancement of the patient's immune responses to the tumor. There are two anti-CTLA-4 monoclonal antibodies undergoing advanced testing currently and they may be approved by the Federal Drug Administration soon, which would make them available outside of clinical trials.