Randomised trial of interferon α-2a as adjuvant therapy in resected primary melanoma thicker than 1•5 mm without clinically detectable node metastases

Background Owing to the limited efficacy of therapy on melanoma at the stage of distant metastases, a well-tolerated adjuvant therapy is needed for patients with high-risk primary melanoma, Our hypothesis was that an adjuvant treatment with low doses of interferon a could be effective in patients with localised melanoma. Methods After resection of a primary cutaneous melanoma thicker than 1.5 mm, patients without clinically detectable node metastases were randomly assigned to receive either 3x10(6) IU interferon alpha-2a, three-times weekly for 18 months, or no treatment. The primary endpoint was the relapse-free interval. Findings 499 patients were enrolled, of whom 489 were eligible. When used as part of a sequential procedure, interferon a-2a was of significant benefit for relapse-free interval (p=0.038). A long-term analysis, after a median follow-up of 5 years, showed a significant extension of relapse-free interval (p=0.035) and a clear trend towards an increase in overall survival (p=0.059) in interferon alpha-2a-treated patients compared with controls. There were 100 relapses and 59 deaths among the 244 interferon alpha-2a-treated patients compared with 119 relapses and 76 deaths among the 245 controls. The estimated 3-year-relapse rates were 32% in the interferon alpha-2a group and 44% in controls; the 3-year death rates were 15% and 21%, respectively. Only 10% of patients experienced WHO grade 3 or 4 adverse events. Treatment was compatible with normal daily life. Interpretation Adjuvant therapy of high-risk melanoma with low doses of interferon a-2a for 18 months is safe and is beneficial when started before clinically detectable node metastases develop.