Adjuvant treatment with pegylated interferon α-2a versus low-dose interferon α-2a in patients with high-risk melanoma: a randomized phase III DeCOG trial

Pegylated-interferon (IFN)-alpha did not improve the outcome over low-dose IFN-alpha in the adjuvant treatment of intermediate and high-risk melanoma patients. A higher percentage of patients under pegylated-IFN-alpha discontinued treatment due to toxicity.Adjuvant treatment with interferon (IFN)-alpha-2a improved disease-free survival (DFS) and showed a trend for improving overall survival (OS) in melanoma. This trial was designed to examine whether PEG-IFN is superior to IFN with regard to distant metastasis-free survival (DMFS), DFS and OS. In this multicenter, open-label, prospective randomized phase III trial, patients with resected cutaneous melanoma stage IIA(T3a)-IIIB (AJCC 2002) were randomized to receive PEG-IFN (180 mu g subcutaneously 1x/week;24 months) or IFN alpha-2a (3MIU subcutaneously 3x/week;24 months). Randomization was stratified for stage, number of metastatic nodes, age and previous IFN treatment. The primary end point was DMFS;secondary end points were OS, DFS, quality of life (QoL) and tolerability. A total of 909 patients were enrolled (451 PEG-IFN versus 458 IFN). Neither 5-year DMFS [PEG-IFN 61.0% versus IFN 67.3%;hazard ratio (HR) 1.16, P = 0.21] nor 5-year OS (PEG-IFN 73.2% versus IFN 75.2%;HR 1.05, P = 0.70) nor 5-year DFS (PEG-IFN 57.3% versus IFN 60.9%;HR 1.09, P = 0.40) showed significant differences. Subgroup analyses in patients +/- ulcerated primaries and of different tumor stages did not find differences in DMFS, OS or DFS between the treatment groups. One hundred and eighteen patients (26.2%) in the PEG-IFN and 61 patients (13.3%) in the IFN population did not receive the full dosage and length of treatment due to adverse events (P < 0.001). Leukopenia and elevation of liver enzymes were more common in the PEG-IFN arm (56% versus 23.5% LCP;19.1% versus 9.4% AST;33.0% versus 16.5% ALT). QoL was identical for nearly all domains. PEG-IFN did not improve the outcome over IFN. A higher percentage of patients under PEG-IFN discontinued treatment due to toxicity. NCT00204529.