Phase II Pilot Study of Intravenous High-Dose Interferon With or Without Maintenance Treatment in Melanoma at High Risk of Recurrence

High-dose interferon alfa-2b (HDI) has emerged as a potentially effective adjuvant therapy in patients with resected melanoma at high risk of recurrence. Evidence suggests it may be the early, very-high-dose part of the regimen that is critical. This pilot study sought to provide an early indication of whether the same effects can be achieved with the intravenous component of HDI alone and inform the feasibility and design of a phase III trial. Patients with stage 2B, 2C, 3B, and 3C melanoma were randomly assigned to receive interferon alfa-2b (IFN-α-2b) 20 MIU/m(2) intravenously (IV) daily 5 days per week for 4 weeks (arm A) versus the same regimen followed by IFN-α-2b 10 MIU/m(2) administered subcutaneously three times per week for 48 weeks (arm B) and observed for relapse-free survival (RFS) and overall survival. Between 2003 and 2009, 194 patients were enrolled (arm A, 96; arm B, 98). After median follow-up of 39.5 months, RFS was 22.7 months (95% CI, 14.1 to 38.1 months) in arm A versus 33.3 months (95% CI, 18.2 to not reached) in arm B (P = .28). The proportions of patients free of relapse at 2 years were 50% and 54.1% (P = .569; hazard ratio, 0.89), respectively. Overall survival favored arm B (median, 41.5 months v not reached; P = .05). Clinical outcomes were better in patients who had the longer regimen. Our results do not support either the use of a month of IV HDI alone in place of the year-long regimen or the initiation of a larger trial on this question.