IFN-α in the Treatment of Melanoma

Among the IFNs, IFN-alpha 2 has been the most broadly evaluated clinically. At the molecular level, IFN-alpha has multiple effects in a variety of malignancies that range from antiangiogenic to potent immunoregulatory, differentiation-inducing, antiproliferative, and proapoptotic effects. A multitude of IFN-alpha 2 regimens that may be classified as low dose, intermediate dose, and high dose have been evaluated as adjuvant therapy in melanoma. A durable impact on both relapse-free and overall survival was seen only with the regimen utilizing high-dose IFN-alpha 2b tested in the Eastern Cooperative Oncology Group and intergroup trials E1684, E1690, and E1694 as adjuvant therapy for high-risk surgically resected melanoma (stage IIB or III). Adjuvant pegylated IFN-alpha 2b has also been evaluated at maximally tolerable doses compared with the observation group in the European Organization for Research and Treatment of Cancer trial 18991 and has shown relapse-free survival benefits in patients with microscopic nodal disease. The Journal of Immunology, 2012, 189: 3789-3793.