Adjuvant interferon in high-risk melanoma: The AIM HIGH Study-United Kingdom Coordinating Committee on cancer research randomized study of adjuvant low-dose extended-duration interferon Alfa-2a in high-risk resected malignant melanoma

PURPOSE: To evaluate low-dose extended duration interferon alfa-2a as adjuvant therapy in patients with thick (> or = 4 mm) primary cutaneous melanoma and/or locoregional metastases. PATIENTS AND METHODS: In this randomized controlled trial involving 674 patients, the effect of interferon alfa-2a (3 megaunits three times per week for 2 years or until recurrence) on overall survival (OS) and recurrence-free survival (RFS) was compared with that of no further treatment in radically resected stage IIB and stage III cutaneous malignant melanoma. RESULTS: The OS and RFS rates at 5 years were 44% (SE, 2.6) and 32% (SE, 2.1), respectively. There was no significant difference in OS or RFS between the interferon-treated and control arms (odds ratio [OR], 0.94; 95% CI, 0.75 to 1.18; P =.6; and OR, 0.91; 95% CI, 0.75 to 1.10; P =.3; respectively). Male sex (P =.003) and regional lymph node involvement (P =.0009), but not age (P =.7), were statistically significant adverse features for OS. Subgroup analysis by disease stage, age, and sex did not show any clear differences between interferon-treated and control groups in either OS or RFS. Interferon-related toxicities were modest: grade 3 (and in only one case, grade 4) fatigue or mood disturbance was seen in 7% and 4% respectively, of patients. However, there were 50 withdrawals (15%) from interferon treatment due to toxicity. CONCLUSION: The results from this study, taken in isolation, do not indicate that extended-duration low-dose interferon is significantly better than observation alone in the initial treatment of completely resected high-risk malignant melanoma.