Background: Several randomised trials have compared interferon-α with control as adjuvant therapy for high-risk malignant melanoma. The results of the individual trials have been either inconclusive or even apparently conflicting, To assess all the available evidence we performed a meta-analysis of these trials. Methods: Standard methods for quantitative meta-analysis based on published data were used. Endpoints evaluated were recurrence-free survival and overall survival. A subgroup analysis by dose of interferon-α was performed. Findings: Twelve trials, comprising 14 comparisons of interferon-α with control, with results available were identified. Recurrence-free survival was improved with interferon-α: hazard ratio 0.83, 95% confidence interval 0.77 to 0.90, p = 0.000003. The benefit on overall survival was less clear (0.93, 0.85 to 1.02, p = 0.1) and the confidence interval is compatible both with no benefit and with a moderate, but clinically worthwhile, benefit. There was some evidence of a dose response relationship with a significant trend for the benefit of interferon-α to increase with increasing dose for recurrence-free survival (test for trend: p = 0.02) but not for overall survival (trend: p = 0.8). Interpretation: This meta-analysis provides the most reliable synthesis of the data currently available, Adjuvant interferon-α produces clear reductions in recurrence of high-risk melanoma, with some evidence of an effect of dose of interferon-α, but it is unclear whether this translates into a worthwhile survival benefit or not. Additional and more mature data are needed to resolve these issues and an individual patient data meta-analysis should be performed.

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Keywords Interferon-α, Melanoma, Meta-analysis, Randomised controlled trials
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Journal Cancer Treatment Reviews
Wheatley, K, Ives, N, Hancock, B, Gore, M, Eggermont, A.M.M, & Suciu, S. (2003). Does adjuvant interferon-α for high-risk melanoma provide a worthwhile benefit? A meta-analysis of the randomised trials. Cancer Treatment Reviews (Vol. 29, pp. 241–252). doi:10.1016/S0305-7372(03)00074-4