Systemic therapy of malignant melanoma

The present status of medical treatment of malignant melanoma is briefly reviewed, both with regard to adjuvant therapy for individuals with high-risk melanoma and a high probability of harbouring subclinical micrometastases, as well as to therapy for establised disseminated (macrometastatic) disease. At present, disseminated, macrometastatic melanoma is incurable in the majority of cases. Single agent chemotherapy has modest effects and results in disease remission in a minority of patients, usually of short duration, Combination chemotherapy, or the combination of chemotherapeutic drugs and cytokines, results in increased response rates and occasionally remissions of prolonged duration. So far, no regimen has demonstrated improved survival compared to single agent therapy in disseminated melanoma. New insights into the mechanisms of resistance to chemotherapeutic drugs may lead to development of predictive tests that can identify individuals with tumors sensitive to a specific agent, as well as to the development of strategies to circumvent drug resistance. It has recently been shown that adjuvant therapy of high-risk melanoma with large doses of interferon-alpha ab significantly prolongs relapse-free and overall survival, at the price of considerable toxicity. Ongoing studies aim to define the optimum dose and duration of adjuvant interferon therapy. Recent advances in molecular biology and immunology may lead to the development of new treatment modalities, such as improved vaccines and other biologic therapies, which may benefit patients with malignant melanoma.