Chemotherapy and Biologic Agents

Dacarbazine, platinum analogues, nitrosoureas, and tubular toxins have all shown some response, but the response is almost universally short and partial. Patients with skin, subcutaneous, lymph node, and occasionally lung are more likely to have a response. These patients are also the group most likely to benefit from aggressive surgical resections. Some of the agents are now available as outpatient regimens.

No combination chemotherapy has been proven more advantageous than to DTIC alone. DTIC has a 20% response rate but, as with other chemotherapeutic regimens, this has not been durable. One combination known as the "Dartmouth Regimen" or CBDT (carmustine (BCNU), cisplatin, DTIC, and tamoxifen) had some initial favorable results and is favored by many oncologists. Phase II and Phase III studies are ongoing to determine if there is an advantage of CBDT to DTIC alone.

Interleukin-2 does not have direct antitumor effects. Interleukin-2 directly affects T lymphocytes, causing their proliferation. Because of the importance of T lymphocytes in animal models of melanoma rejection, interleukin-2 is widely used in melanoma research for the proliferation of antimelanoma lymphocytes. The use of IL-2 has spread into human trials, and this cytokine is a part of many ongoing immunotherapy trials. Interleukin-2 therapy alone has a 7% complete response rate that is sustained in 3/4 of patients, but use of interleukin-2 is limited by severe systemic toxicity. Biologic agents such as tumor vaccines and cytokines are now being combined. These clinical trials are ongoing and results are too preliminary to make recommendations for therapy.

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