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

• Published in: Journal of clinical oncology Vol. 22; no. 1; pp. 53 - 61
• Main Authors: HANCOCK, B. W, WHEATLEY, K, BURROWS, L, GORE, M, HARRIS, S, IVES, N, HARRISON, G, HORSMAN, J. M, MIDDLETON, M. R, THATCHER, N, LORIGAN, P. C, MARSDEN, J. R
• Format: Journal Article
• Language: English
• Published: Baltimore, MD American Society of Clinical Oncology 01.01.2004; Lippincott Williams & Wilkins
• Subjects: Adolescent; Adult; Affect - drug effects; Age Factors; Aged; Aged, 80 and over; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - adverse effects; Antineoplastic Agents - therapeutic use; Biological and medical sciences; Dermatology; Disease-Free Survival; Dose-Response Relationship, Drug; Drug Administration Schedule; Fatigue - chemically induced; Female; Humans; Interferon-alpha - administration & dosage; Interferon-alpha - adverse effects; Interferon-alpha - therapeutic use; Male; Medical sciences; Melanoma - drug therapy; Melanoma - pathology; Melanoma - surgery; Middle Aged; Risk Factors; Skin Neoplasms - drug therapy; Skin Neoplasms - pathology; Skin Neoplasms - surgery; Treatment Outcome; Tumors; Tumors of the skin and soft tissue. Premalignant lesions; United Kingdom; Europe; High risk; Randomization; Cancerology; Alpha interferon; Low dose; Malignant melanoma; Adjuvant; Research; Malignant tumor
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/JCO.2004.03.185

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. 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. 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. 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.