title: Intravenous high-dose interferon with or without maintenance treatment in melanoma at high risk of recurrence: meta-analysis of three trials.
abstract: Resected stage IIB-IIIC malignant melanoma has a poor prognosis with a high risk of relapse and death. Treatment with adjuvant interferon alfa-2b (IFN-α-2b) is associated with improved relapse-free and overall survivals (OS), but the most appropriate dose and duration of treatment are unknown. In this article, we present an individual patient data random effects meta-analysis of melanoma patients from the U.K., Greek, and Chinese randomized trials. All patients were randomized either to IFN-α-2b 15-20 MIU/m(2) IV daily 5 days per week for 4 weeks (IV) or to the same regimen followed by IFN-α-2b 9-10 MIU/m(2) administered three times per week for 48 weeks (IV and SC). Allowing for dose interruptions and reductions, an equivalent total dose of IFN-α-2b was delivered in all three studies. We assessed whether IV was noninferior to IV and SC in terms of relapse-free survival (RFS) and investigated tumor and patient characteristics that impacted on outcomes. Median follow-up of 716 stage IIB-IIIC patients was 5.4 years. Noninferiority of IV compared to IV and SC could not be conferred for RFS (hazard ratio [HR] 1.16, 95% confidence interval [CI] 0.89-1.52; noninferior P = 0.17). Stage (P < 0.0001), site (acral vs. other, P < 0.0001), and Breslow thickness (P = 0.02) were significant predictors of RFS. The HR for death was 1.13 for IV compared to IV and SC, (95% CI 0.91-1.39). Stage (P < 0.0001) and Breslow thickness (P = 0.001) were significant independent predictors of OS. The available data suggest that where adjuvant high-dose interferon is being considered there is no evidence to deviate from the year long regimen described in the Eastern Cooperative Oncology Group and Intergroup studies.
authors.affiliation: National Institute for Health Research Biomedical Research Centre, Oxford University Hospitals NHS Trust, Oxford, United Kingdom.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Malczewski
authors.affiliation: Warwick Clinical Trials Unit, University of Warwick, Coventry, United Kingdom.
authors.forename: Andrea
authors.initials: A
authors.lastname: Marshall
authors.affiliation: National Institute for Health Research Biomedical Research Centre, Oxford University Hospitals NHS Trust, Oxford, United Kingdom.
authors.forename: Miranda J
authors.initials: MJ
authors.lastname: Payne
authors.affiliation: Department of Renal Cancer and Melanoma, Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Peking University Cancer Hospital & Institute, Beijing, China.
authors.forename: Lili
authors.initials: L
authors.lastname: Mao
authors.affiliation: Hellenic Co-operative Oncology Group, Athens, Greece.
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Bafaloukos
authors.affiliation: Department of Renal Cancer and Melanoma, Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Peking University Cancer Hospital & Institute, Beijing, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Si
authors.affiliation: Hellenic Co-operative Oncology Group, Athens, Greece.
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Pectasides
authors.affiliation: Hellenic Co-operative Oncology Group, Athens, Greece.
authors.forename: George
authors.initials: G
authors.lastname: Fountzilas
authors.affiliation: Department of Renal Cancer and Melanoma, Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Peking University Cancer Hospital & Institute, Beijing, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Guo
authors.affiliation: Hellenic Co-operative Oncology Group, Athens, Greece.
authors.forename: Helen
authors.initials: H
authors.lastname: Gogas
authors.affiliation: National Institute for Health Research Biomedical Research Centre, Oxford University Hospitals NHS Trust, Oxford, United Kingdom.
authors.forename: Mark R
authors.initials: MR
authors.lastname: Middleton
mesh_terms: D061605:Administration, Intravenous; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D017024:Chemotherapy, Adjuvant; D002986:Clinical Trials as Topic; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage; D007372:Interferons / Q000008:administration & dosage*; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D016016:Proportional Hazards Models; D011994:Recombinant Proteins / Q000008:administration & dosage*
chemical_list: D000970:Antineoplastic Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D007372:Interferons
keywords: Adjuvant; interferon; melanoma; meta-analysis; survival