Intravenous high-dose interferon with or without maintenance treatment in melanoma at high risk of recurrence: meta-analysis of three trials

Journal article

Resected stage IIB–IIIC malignant melanoma has a poor prognosis with a high risk of relapse and death. Treatment with adjuvant interferon alfa-2b (IFN-α-2b) is associated with improved relapse-free and overall survivals (OS), but the most appropriate dose and duration of treatment are unknown. In this article, we present an individual patient data random effects meta-analysis of melanoma patients from the U.K., Greek, and Chinese randomized trials. All patients were randomized either to IFN-α-2b 15–20 MIU/m2 IV daily 5 days per week for 4 weeks (IV) or to the same regimen followed by IFN-α-2b 9–10 MIU/m2 administered three times per week for 48 weeks (IV and SC). Allowing for dose interruptions and reductions, an equivalent total dose of IFN-α-2b was delivered in all three studies. We assessed whether IV was noninferior to IV and SC in terms of relapse-free survival (RFS) and investigated tumor and patient characteristics that impacted on outcomes. Median follow-up of 716 stage IIB–IIIC patients was 5.4 years. Noninferiority of IV compared to IV and SC could not be conferred for RFS (hazard ratio [HR] 1.16, 95% confidence interval [CI] 0.89–1.52; noninferior P = 0.17). Stage (P < 0.0001), site (acral vs. other, P < 0.0001), and Breslow thickness (P = 0.02) were significant predictors of RFS. The HR for death was 1.13 for IV compared to IV and SC, (95% CI 0.91–1.39). Stage (P < 0.0001) and Breslow thickness (P = 0.001) were significant independent predictors of OS. The available data suggest that where adjuvant high-dose interferon is being considered there is no evidence to deviate from the year long regimen described in the Eastern Cooperative Oncology Group and Intergroup studies.

Authors: Malczewski, A; Marshall, A; Payne, M; Mao, L; Bafaloukos, D

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: John Wiley and Sons Ltd
• Journal: Cancer Medicine
• Volume: 5
• Issue: 1
• Pages: 17–23
• Publication date: 2015-01-01
• DOI: 10.1002/cam4.563
• ISSN: 2045-7634
• Keywords: interferon; adjuvant; meta-analysis; melanoma; survival