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

J. A. Sparano, R. I. Fisher, M. Sunderland, K. Margolin, M. L. Ernest, M. Sznol, M. B. Atkins, J. P. Dutcher, K. C. Micetich, G. R. Weiss, J. H. Doroshow, F. R. Aronson, L. V. Rubinstein, J. W. Mier

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Purpose: 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-α) with high-dose IL-2 alone in patients with advanced melanoma in a randomized phase III trial design. Patients and Methods: Eighty-five patients with advanced melanoma were randomly assigned to receive IL-2 6 x 106 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 106 U/m2 per dose, plus IFN-α 3 x 106 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- α (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-α (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-α 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-α arm was less than 25%. Conclusion: Using the preparation, dose, and schedule of IL-2 in our trial, IFN-α failed to enhance significantly the response rate to high- dose IL-2 in the treatment of patients with advanced melanoma.

Original languageEnglish (US)
Pages (from-to)1969-1977
Number of pages9
JournalJournal of Clinical Oncology
Issue number10
Publication statusPublished - Jan 1 1993


ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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