RANDOMIZED TRIAL OF INTERFERON ALPHA-2A AS ADJUVANT THERAPY IN RESECTED PRIMARY MELANOMA THICKER THAN 1-CENTER-DOT-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 nee ded for patients with high-risk primary melanoma, Our hypothesis was t hat an adjuvant treatment with low doses of interferon a could be effe ctive in patients with localised melanoma. Methods After resection of a primary cutaneous melanoma thicker than 1.5 mm, patients without cli nically detectable node metastases were randomly assigned to receive e ither 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 signifi cant 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 increa se in overall survival (p=0.059) in interferon alpha-2a-treated patien ts compared with controls. There were 100 relapses and 59 deaths among the 244 interferon alpha-2a-treated patients compared with 119 relaps es 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; t he 3-year death rates were 15% and 21%, respectively. Only 10% of pati ents experienced WHO grade 3 or 4 adverse events. Treatment was compat ible with normal daily life. Interpretation Adjuvant therapy of high-r isk melanoma with low doses of interferon a-2a for 18 months is safe a nd is beneficial when started before clinically detectable node metast ases develop.