High-dose chemotherapy and autologous stem cell support for patients with malignant melanoma

High-dose chemotherapy (HDC) with autologous stem cell support has led to improved response rates, and in some cases, improved survival in a variety of different malignancies. Since alkylating agents are the most active class of compounds in malignant melanoma, attempts have been made to dose-intensify therapy using autologous bone marrow for hematologic support. Numerous phase I/II studies of different alkylating agents, either alone or in combination, have been reported. These results are characterized by high overall response rates, compared to lower-dose therapy, but few complete responses and disappointingly short remission durations. Some studies indicate that tumors in the skin or lymph nodes are more responsive to this approach than visceral or bone metastases. A single trial of HDC in the high-risk, surgical adjuvant setting showed that time to progression was more than doubled, although the result was not statistically significant because of the low power of the trial. More encouraging results may come from the combination of the cytoreductive capacity of HDC combined with immune augmentation from IL-2, interferon or similar cytokines, especially when combined with peripheral blood progenitor cells which induce faster recovery of the immune system.