Randomized dose-escalation study evaluating peginterferon alfa-2a in patients with metastatic malignant melanoma

Purpose A pegylated interferon, peginterferon alfa-2a (PEG-IFN alpha-2a; 40 kd), has the potential for improved tumor response and survival with lower toxicity than IFN alpha. This open-label, randomized study evaluated the safety, tolerability, and efficacy of subcutaneous PEG-IFN alpha-2a in patients with metastatic malignant melanoma (stage IV American Joint Committee on Cancer staging system). Patients and Methods PEG-IFN alpha-2a was administered subcutaneously at 180 (n = 48), 360 (n = 53), or 450 mu g (n = 49) once weekly for 24 weeks, with maintenance therapy for responders. Efficacy was assessed by the proportion of patients with complete response (CR) or partial response (PR). Results The major response rate (CR or PR) was 6% in the 180-mu g group (CR, 2%; PR, 4%), 8% in the 360-mu g group (CR, 2%, PR, 6%), and 12% in the 450-mu g group (CR, 6%; PB, 6%). The times to achieve a major response, duration of major response, rate of disease progression, and 12-month survival were similar between groups, although overall median survival was significantly different among the three groups (P = .0136). More patients required dose adjustment for safety reasons in the higher dose groups, but PEG-IFN alpha-2a was generally well tolerated, with few withdrawals because of adverse events (6%, 19%, and 16% in the 180-, 360-, and 450-mu g groups, respectively). The most common adverse events were fatigue, pyrexia, and nausea. Conclusion PEG-IFN alpha-2a at doses up to 450 mu g once weekly has shown good tolerability and similar efficacy to conventional IFN alpha and monochemotherapy in stage IV metastatic melanoma.