Pegylated interferon alpha-2b as adjuvant treatment of Stage III malignant melanoma: an evidence-based review

INTRODUCTION: Stage III melanoma, also referred to as regional metastatic melanoma, has five-year survival rates ranging between 40% and 78%. In order to reduce the likelihood of recurrence in this high-risk population, patients undergo resection of primary tumors and all involved nodal basins. Systemic therapy is being pursued in an effort to improve outcome data, but the best strategy has yet to be defined. Interferon alpha-2b remains to date the most promising approach available. Toxicities and intensive intravenous administration, unfortunately, are major concerns. An alternative is the use of interferon in its pegylated subcutaneous form. The aim of this research was to review the evidence for the use of pegylated interferon alpha-2b in Stage III malignant melanoma. EVIDENCE REVIEW: ECOG 1684 was the pivotal trial that first demonstrated a statistically significant benefit in relapse-free and overall survival for adjuvant interferon alpha-2b in high-risk melanoma. Other larger studies, such as ECOG 1690, confirmed a relapse-free survival benefit but did not achieve statistical significance for overall survival. The first study of the pegylated form of interferon alpha-2b in Stage III melanoma, EORTC 18991, is reviewed here. This trial showed a statistically significant improvement in relapse-free survival but not overall survival. Encouraging data of potential equivalent efficacy, easier administration, and fewer Grade 3 and 4 adverse reactions compared with high-dose intravenous interferon raises the question of its potential role in Stage III melanoma in the adjuvant setting.