Does pegylated interferon alpha-2b confer additional benefit in the adjuvant treatment of high-risk melanoma?

High-dose interferon (IFN)alpha-2b has shown benefits in the adjuvant treatment of melanoma, but relapse-free and overall survival remain poor, despite the use of chemotherapy, vaccines, and combinations of these modalities. Questions remain in relation to the relative importance of dose, route and duration of immunotherapy needed to prevent relapse and improve survival. Our understanding of STAT signaling, the role of dendritic and T cells and of circulating cytokine profiles in this benefit of IFN therapy have yet to be deployed clinically. The EORTC 18991 trial analyzed whether pegylated IFNalpha-2b delivered for up to 5 years could improve tolerability and efficacy of IFN. The study demonstrated an improvement in a subset of patients with microscopic disease, but not in those with gross nodal involvement. The potential role of this agent needs to be examined in relation to the long-term control of relapse. Assessment of the molecular, immunological, and antiangiogenic effects of the various forms of pegylated IFN will be critical to identification of the best future applications for these modalities.