title: 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.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Medicine V, University of Heidelberg, Germany. ulrich_keilholz@krzmail.krz.uni-heidelberg.de
authors.forename: U
authors.initials: U
authors.lastname: Keilholz
authors.forename: S H
authors.initials: SH
authors.lastname: Goey
authors.forename: C J
authors.initials: CJ
authors.lastname: Punt
authors.forename: T M
authors.initials: TM
authors.lastname: Proebstle
authors.forename: R
authors.initials: R
authors.lastname: Salzmann
authors.forename: C
authors.initials: C
authors.lastname: Scheibenbogen
authors.forename: D
authors.initials: D
authors.lastname: Schadendorf
authors.forename: D
authors.initials: D
authors.lastname: Liénard
authors.forename: A
authors.initials: A
authors.lastname: Enk
authors.forename: R
authors.initials: R
authors.lastname: Dummer
authors.forename: B
authors.initials: B
authors.lastname: Hantich
authors.forename: A M
authors.initials: AM
authors.lastname: Geueke
authors.forename: A M
authors.initials: AM
authors.lastname: Eggermont
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002945:Cisplatin / Q000008:administration & dosage; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005060:Europe; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage; D008207:Lymphatic Metastasis; D008545:Melanoma / Q000188:drug therapy* / Q000556:secondary*; D011994:Recombinant Proteins; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000469:parasitology*; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D002945:Cisplatin