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

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 × 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 × 10⁶ U/m² per dose, plus IFN-α 3 × 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.