title: U.S. Food and Drug Administration Approval: peginterferon-alfa-2b for the adjuvant treatment of patients with melanoma.
abstract: On March 29, 2011, the U.S. Food and Drug Administration approved peginterferon alfa-2b (PEG-IFN) (Sylatron™; Schering Corporation, Kenilworth, NJ) for the adjuvant treatment of melanoma patients with microscopic or gross nodal involvement following definitive surgical resection including complete lymphadenectomy. The approval was based on a single, open-label, multicenter trial enrolling 1,256 patients. After surgical resection, patients were randomized (1:1) to either PEG-IFN or observation for 5 years. PEG-IFN, 6 μg/kg per week, was administered s.c. for eight doses, followed by 3 μg/kg per week for up to 252 weeks. Stratification factors included microscopic or gross nodal involvement, number of positive nodes, Breslow thickness, ulceration, sex, and study center. Patients were assessed for recurrence by the investigators based on physical examination every 3 months for 2 years and every 6 months thereafter. The relapse-free survival (RFS) interval, the primary efficacy endpoint, was significantly longer in PEG-IFN-treated patients. The median RFS times were 34.8 months and 25.5 months, respectively. There was no statistically significant difference in the overall survival time. The most common (>60%) grade 1-4 adverse reactions were fatigue, increased alanine aminotransferase (ALT) and aspartate aminotransferase (AST), pyrexia, headache, anorexia, myalgia, nausea, chills, and injection site reactions. The most common serious adverse reactions were fatigue, increased ALT and AST, and pyrexia. Thirty-three percent of patients receiving PEG-IFN discontinued treatment as a result of adverse reactions. Five deaths were reported within 30 days of the last treatment dose, two resulting from cardiovascular disease considered as possibly related to treatment.
authors.affiliation: Division of Biological Oncology Products, Food and Drug Administration, 10903 New Hampshire Avenue, Building 22, Room 5222, Silver Spring, Maryland 20993, USA. Thomas.Herndon@fda.hhs.gov
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Herndon
authors.forename: Suzanne G
authors.initials: SG
authors.lastname: Demko
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Jiang
authors.forename: Kun
authors.initials: K
authors.lastname: He
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Gootenberg
authors.forename: Martin H
authors.initials: MH
authors.lastname: Cohen
authors.forename: Patricia
authors.initials: P
authors.lastname: Keegan
authors.forename: Richard
authors.initials: R
authors.lastname: Pazdur
mesh_terms: D017024:Chemotherapy, Adjuvant; D017277:Drug Approval; D005260:Female; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000601:surgery; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000009:adverse effects; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000601:surgery; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; C417083:peginterferon alfa-2b