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Interferon Alfa Therapy for Malignant Melanoma: A Systematic Review of Randomized Controlled Trials

From the Center for Evidence-Based Medicine, University of Oxford, Nuffield Department of Clinical Medicine, Oxford Radcliffe National Health Service Trust, Oxford, United Kingdom.

Address reprint requests to Marko B. Lens, MD, Centre for Evidence-Based Medicine, University of Oxford, Nuffield Department of Clinical Medicine, Oxford Radcliffe NHS Trust, Oxford OX3 9DU, United Kingdom; email: markolens{at}aol.com

PURPOSE: No standard systemic adjuvant therapy has been proven to increase overall survival in melanoma patients. The effect of interferon alfa (IFN) as a single agent or in combination has been widely explored in clinical trials. The purpose of this study was to assess the benefit of IFN therapy in malignant melanoma.

METHODS: We performed a systematic review of randomized controlled trials comparing regimens with or without IFN adjuvant therapy in melanoma patients. We assessed the effect of IFN therapy on overall survival (OS), disease-free survival (DFS), melanoma recurrences, and toxicity. The quality of each trial was systematically evaluated.

RESULTS: Nine randomized controlled trials (RCTs) of IFN therapy in melanoma patients were identified. Eight were published and one was unpublished. Eight trials comprising 3,178 patients fulfilled our inclusion criteria and were analyzed. Quality assessment scores ranged from 22 to 71, with a mean score of 55.4 (95% confidence interval, 53.8 to 57.0). For OS, only one trial reported a statistically significant benefit for IFN, but our analysis did not confirm it. Two trials reported statistically significant benefit in DFS for the patients treated with IFN, but our analysis confirmed it in only one trial. There was a wide clinical heterogeneity between included trials, making meta-analysis inappropriate.

CONCLUSION: In our review, results from included RCTs demonstrated no clear benefit of IFN therapy on OS in melanoma patients. A large RCT is required to answer whether a full regimen of IFN therapy is effective and to identify the subgroups of patients who might benefit from IFN treatment.

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