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Randomized Dose-Escalation Study Evaluating Peginterferon Alfa-2a in Patients With Metastatic Malignant Melanoma

From the Department of Dermatology, University Hospital of Zürich, Zürich, Switzerland; Department of Dermatology, Eberhard-Karls University, Tübingen, Germany; Department of Medicine, University of Washington, Seattle, WA; Department of Surgical Oncology, Daniel den Hoed Cancer Centre, University Hospital Rotterdam, Rotterdam, The Netherlands; and Departments of Biostatistics and Medical Science, Hoffmann-LaRoche Inc, Nutley, NJ.

Address reprint requests to Reinhard Dummer, MD, Dermatologische Klinik, Universitätsspital Zürich, Gloriastrasse 31, 8091 Zürich, Switzerland; e-mail: reinhard.dummer{at}usz.ch

PURPOSE: A pegylated interferon, peginterferon alfa-2a (PEG-IFN-2a; 40 kd), has the potential for improved tumor response and survival with lower toxicity than IFN. This open-label, randomized study evaluated the safety, tolerability, and efficacy of subcutaneous PEG-IFN-2a in patients with metastatic malignant melanoma (stage IV American Joint Committee on Cancer staging system).

PATIENTS AND METHODS: PEG-IFN-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-IFN-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-IFN-2a at doses up to 450 µg once weekly has shown good tolerability and similar efficacy to conventional IFN and monochemotherapy in stage IV metastatic melanoma.

Supported in part by the Swiss National Science Foundation (Grant No. 3100A0-103671-1 to R.D.) and by the Gottfried und Julia Bangerter-Rhyner Stiftung (R.D.).

Presented in part at the European Cancer Conference, Copenhagen, Denmark, September 19-25, 2003, the 39th Annual Meeting of the American Society of Clinical Oncology, May 31-June 3, 2003, Chicago, IL; and 9th World Congress on Cancers of the Skin, Seville, Spain, May 7-11, 2003.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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