Purpose: Metastatic melanoma and current treatments are reviewed.

Summary: Despite the many advances in cancer treatment that have occurred over the last several decades, the prognosis for patients with advanced melanoma remains poor. The 5-year survival rate for patients with distant metastases is less than 10%. For these patients, surgery and radiation therapy are primarily used to palliate symptoms. Most patients with advanced melanoma receive systemic therapy. Single-agent cytotoxic chemotherapy with dacarbazine is the standard of care in community practice, although the response rate is generally low and few patients attain complete remission. Temozolomide is an orally active congener of dacarbazine that is at least as effective as dacarbazine when used as single-agent cytotoxic therapy. Low-dose extended temozolomide regimens may provide greater antitumor efficacy. Combinations of dacarbazine or temozolomide with other cytotoxic therapies have not markedly improved patient survival. Newer agents (e.g., lomeguatrib and decitabine) have been developed to overcome mechanisms of drug resistance. Biotherapy using high-dose interleukin-2 has been shown to induce durable responses lasting 5 years or more in some patients, although the overall response rate is not substantially better than that with dacarbazine. Interferon alpha is also used for the treatment of metastatic melanoma, despite lack of approval by the FDA for this indication. Some evidence suggests that combining chemotherapy and biotherapy agents (biochemotherapy) increases the rate of treatment response but does not significantly extend overall survival.

Conclusion: New strategies are needed to improve treatment response rates and duration of overall survival in patients with metastatic melanoma.