Journal of Clinical Oncology, Vol 15, 2579-2588, Copyright © 1997 by American Society of Clinical Oncology
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
U Keilholz, SH Goey, CJ Punt, TM Proebstle, R Salzmann, C Scheibenbogen, D Schadendorf, D Lienard, A Enk, R Dummer, B Hantich, AM Geueke and AM Eggermont
Department of Medicine V, University of Heidelberg, Germany. ulrich_keilholz@krzmail.krz.uni-heidelberg.de
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/m2 subcutaneously on days 1 through 5 and a
high-dose intravenous decrescendo regimen of IL-2 on days 3 through 8 (18
mIU/ m2/6 hours, 18 mIU/m2/12 hours, 18 mIU/m2/24 hours, and 4.5 mIU/m2/24
hours x 3) without (arm A) or with (arm B) CDDP 100 mg/m2 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.
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