Chemotherapy and biologic therapies for melanoma: do they work?

The incidence of melanoma is increasing, and the therapeutic options for unresectable disease are limited, resulting in an increase in the death rate. Melanoma is usually resistant to standard chemotherapy, and the response rate for any single agent or combination of agents is 15% to 25%. High-dose interleukin-2 results in prolonged responses in a minority of patients, and biochemotherapy (combinations of chemotherapy, interferon, and interleukin-2) is associated with an improved response rate, but no clear effect on overall survival. A number of promising new agents have entered clinical trials in recent years, including monoclonal antibodies and small molecule inhibitors that target either the malignant melanocytes or negative regulators of the immune system. These drugs appear to benefit subsets of patients, and identification of predictors of response is the subject of intense research. This contribution summarizes the risks and benefits of older regimens and discusses the newer, targeted therapies.