Interaction of Chemotherapy and Biological Response Modifiers in the Treatment of Melanoma

Abstract

Metastatic melanoma is one of the most drug-resistant human neoplasms. While single-agent cytotoxic drugs generally produce response rates of less than 20%, combination chemotherapy regimens lead to response rates of 20–40%. Durable complete remissions, however, are rare. Biologic response modifiers (biologics) have also shown modest activity when used alone. Interferon-α (IFN-α) and interleukin-2 (IL-2), the most commonly applied biologics in melanoma, produce response rates of approximately 10–20%, with only 3–5% of the patients treated exhibiting durable responses. It remains uncertain whether the combination of IFN-α plus IL-2 is superior to IL-2 alone. Although cytotoxic agents and biologies have limited activity when used alone, the combination of cisplatin-based regimens with IFN-α and IL-2 has shown promising preliminary results, with overall response rates in the 50–60% range. Approximately 10% of these patients have exhibited durable responses. The toxicity of the biochemotherapy regimens is severe, however, and their impact on survival remains to be established in ongoing controlled trials. This chapter focuses on the clinical results of the biochemotherapy regimens and addresses the possible mechanisms of enhanced activity when cytotoxic agents and biologics are combined to overcomed drug-resistant melanoma.