Interferon alfa-2a and interleukin-2 with or without cisplatin in metastatic melanoma: A randomized trial of the European Organization for Research and Treatment of Cancer Melanoma Cooperative Group

Purpose: The combination of interferon alfa-2a (IFN alpha) and high-dose interleukin-2 (IL-2) is active in metastatic melanoma. The addition of cisplatin (CDDP) has resulted in response rates greater than 50%, This study was performed to determine whether the addition of CDDP to a cytokine treatment regimen with IFN alpha and high-dose IL-2 influences survival of patients with metastatic melanoma. Patients and Methods: Patients with advanced metastatic melanoma were randomly assigned to receive treatment with IFN alpha 10 x 10(6) U/m(2) subcutaneously on days 1 through 5 and a high-dose intravenous decrescendo regimen of IL-2 on days 3 through 8 (18 mIU/m(2)/6 hours, 18 mIU/m(2)/12 hours, 18 mIU/m(2)/24 hours, and 4.5 mIU/m(2)/24 hours x 3) without (arm A) or with (arm B) CDDP 100 mg/m(2) on day 1. Treatment cycles were repeated every 28 days to a maximum of four cycles. Results: One hundred thirty-eight patients with advanced metastatic melanoma, of whom 87% had visceral metastases, were accrued for the trial, Both regimens were feasible in a multicenter setting, The objective response rate was 18% without and 33% with CDDP (P = .04). The progression-free survival was 53 days without and 92 days with CDDP (P = .02, Wilcoxon; P = .09, log-rank). There was no statistically significant difference in survival between treatment arms, with a median overall survival duration for all patients of 9 months. Conclusion: The addition of CDDP to cytokine treatment with IFN alpha and IL-2 does not influence survival of patients with advanced metastatic melanoma, despite a significant increase in response rate and progression-free survival. (C) 1997 by American Society of Clinical Oncology.