Management of pegylated interferon alpha toxicity in adjuvant therapy of melanoma

Introduction: Both native IFN alpha 2b and pegylated IFN alpha 2b (PegIFN alpha 2b) are approved for the adjuvant treatment of high-risk melanoma. Areas covered: This review compares the toxicity profiles of high-dose IFN alpha 2b (HDI) and PegIFN alpha 2b, and provides recommendations on the management of common PegIFN alpha 2b-related toxicities, based on available clinical data and published literature. Expert opinion: The toxicity profile of PegIFN alpha 2b at the approved dose (6 mu g/kg/week for 8 weeks then 3 mu g/kg/week for up to 5 years) is qualitatively similar to HDI in melanoma. The most common adverse events (AEs) are fatigue, anorexia, hepatotoxicity, flu-like symptoms, injection site reactions and depression. However, fatigue and flu-like symptoms appear less severe with PegIFN alpha 2b, and toxicity seems to occur earlier, whereas with HDI toxicity may increase with time. Most AEs can be managed effectively by dose modification and aggressive symptom control. Dosing to tolerance using a three-step dose reduction schedule to maintain an ECOG performance status of 0 - 1 may enable patients experiencing toxicity to remain on treatment; this can be applied readily in clinical practice. PegIFN alpha 2b is therefore a valuable alternative option for adjuvant treatment in melanoma, with a toxicity profile similar to that of HDI overall but a more convenient administration schedule.