Sequential chemoimmunotherapy in the treatment of metastatic melanoma

A phase II study that alternates the sequence of chemotherapy (carmustine [BCNU], cisplatin [CDDP], and dacarbazine [DTIC]) and biologic therapy (interleukin-2 [IL-2] and interferon alfa-2 alpha [alpha IFN]) was performed to establish a safe and efficacious way to sequence these forms of treatment for metastatic melanoma.

Patients who had measurable metastatic melanoma, a Karnofsky performance status of greater than or equal to 70, and no clinically significant cardiac or pulmonary dysfunction were eligible for entry onto this trial. Responses to treatment were assessed after a treatment cycle by two tumor evaluations at least 4 weeks apart.

Forty-two consecutive patients with metastatic melanoma were treated with this sequential chemoimmunotherapy. Transient thrombocytopenia and neutropenia were observed frequently, but neither hemorrhage nor infection occurred in any of the patients. Of the 42 patients, 10 achieved a complete response (24%), 14 achieved a partial response (33%), two achieved a minor response (5%), eight had stable disease (19%), and eight (19%) had progressive disease. The median time to disease progression for all patients was 7 months. The median survival for all patients entered onto the trial was 11.5 months. A vitiligo-like depigmentation was induced in many patients by this treatment.

Cytotoxic chemotherapy can be administered safely immediately before or immediately after IL-2 and alpha IFN. Sequential chemoimmunotherapy administered as previously described yields a response rate of more than 55%. The overall survival curve suggests that a proportion of patients may achieve a long-term benefit from this treatment. Also, cutaneous depigmentation induced by this treatment suggests that immune modulation may contribute to the antimelanoma effect of this treatment.