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 ( 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. J Clin Oncol 22:53-61. © 2004 by American Society of Clinical Oncology