title: Randomized phase III trial of treatment with high-dose interleukin-2 either alone or in combination with interferon alfa-2a in patients with advanced melanoma.
abstract: OBJECTIVE
  To compare the response rate, survival, and toxicity of treatment with high-dose intravenous (IV) bolus interleukin-2 (IL-2) plus interferon alfa-2a (IFN-alpha) with high-dose IL-2 alone in patients with advanced melanoma in a randomized phase III trial design.
  
  
  METHODS
  Eighty-five patients with advanced melanoma were randomly assigned to receive IL-2 6 X 10(6) U/m2 per dose every 8 hours as tolerated for a maximum of 14 doses on days 1 through 5 and 15 through 19, or IL-2 4.5 X 10(6) U/m2 per dose, plus IFN-alpha 3 X 10(6) U/m2 using an identical schedule. A planned interim analysis was performed after 85 patients were entered, which forms the basis for this report.
  
  
  RESULTS
  Partial response (PR) occurred in two of 44 patients (5%; 95% confidence interval, 1% to 15%) receiving IL-2 alone, compared with four of 41 patients (10%; 95% confidence interval, 3% to 23%) receiving IL-2/IFN-alpha (P = .30). There were no complete responses (CRs). The median duration of response was 11.5 months (range, 2.0 to 15.7+). There was no significant difference in the median survival duration for patients receiving IL-2 alone (10.2 months) compared with patients receiving IL-2/IFN-alpha (9.7 months). The median and mean number of doses of IL-2 were equivalent in both groups, as was toxicity. There were three treatment-related deaths, two in the IL-2-alone arm and one in the IL-2/IFN-alpha arm. The trial was terminated after the first interim analysis based on predefined early-stopping rules, which included termination if the response rate in the IL-2/IFN-alpha arm was less than 25%.
  
  
  CONCLUSIONS
  Using the preparation, dose, and schedule of IL-2 in our trial, IFN-alpha failed to enhance significantly the response rate to high-dose IL-2 in the treatment of patients with advanced melanoma.
authors.affiliation: Extramural IL-2 Working Group (Albert Einstein Cancer Center/Montefiore Medical Center, Bronx, NY 10467.
authors.forename: J A
authors.initials: JA
authors.lastname: Sparano
authors.forename: R I
authors.initials: RI
authors.lastname: Fisher
authors.forename: M
authors.initials: M
authors.lastname: Sunderland
authors.forename: K
authors.initials: K
authors.lastname: Margolin
authors.forename: M L
authors.initials: ML
authors.lastname: Ernest
authors.forename: M
authors.initials: M
authors.lastname: Sznol
authors.forename: M B
authors.initials: MB
authors.lastname: Atkins
authors.forename: J P
authors.initials: JP
authors.lastname: Dutcher
authors.forename: K C
authors.initials: KC
authors.lastname: Micetich
authors.forename: G R
authors.initials: GR
authors.lastname: Weiss
mesh_terms: D000328:Adult; D000368:Aged; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000627:therapeutic use*; D007376:Interleukin-2 / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008545:Melanoma / Q000628:therapy*; D008875:Middle Aged; D011994:Recombinant Proteins; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000077190:Interferon alpha-2; D016898:Interferon-alpha; D007376:Interleukin-2; D011994:Recombinant Proteins