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

Purpose: A pegylated interferon, peginterferon alfa-2a (PEG-IFNα-2a; 40 kd), has the potential for improved tumor response and survival with lower toxicity than IFNα. This open-label, randomized study evaluated the safety, tolerability, and efficacy of subcutaneous PEG-IFNα-2a in patients with metastatic malignant melanoma (stage IV American Joint Committee on Cancer staging system). Patients and Methods: PEG-IFNα-2a was administered subcutaneously at 180 (n = 48), 360 (n = 53), or 450 μg (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-μg group (CR, 2%; PR, 4%), 8% in the 360-μg group (CR, 2%; PR, 6%), and 12% in the 450-μg group (CR, 6%; PR, 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-IFNα-2a was generally well tolerated, with few withdrawals because of adverse events (6%, 19%, and 16% in the 180-, 360-, and 450-μg groups, respectively). The most common adverse events were fatigue, pyrexia, and nausea. Conclusion: PEG-IFNα-2a at doses up to 450 μg once weekly has shown good tolerability and similar efficacy to conventional IFNα and monochemotherapy in stage IV metastatic melanoma.