title: Interferon alfa-2b adjuvant therapy of high-risk resected cutaneous melanoma: the Eastern Cooperative Oncology Group Trial EST 1684.
abstract: OBJECTIVE
  Interferon alfa-2b (IFN alpha-2b) exhibits antitumor activity in metastatic melanoma and on this basis has been evaluated as an adjuvant therapy following surgery for deep primary (T4) or regionally metastatic (N1) melanoma.
  
  
  METHODS
  A randomized controlled study of IFN alpha-2b (Schering-Plough, Kenilworth, NJ) administered at maximum-tolerated doses of 20 MU/m2/d intravenously (i.v.) for 1 month and 10 MU/m2 three times per week subcutaneously (SC) for 48 weeks versus observation, was conducted by the Eastern Cooperative Oncology Group (ECOG) in 287 patients.
  
  
  RESULTS
  A significant prolongation of relapse-free survival (P = .0023, one-sided) and prolongation of overall survival (P = .0237, one-sided) was observed with IFN alpha-2b therapy in this trial, which is now mature with a median follow-up time of 6.9 years. The impact of treatment on relapse rate is most pronounced early during the treatment interval. The overall benefit of treatment in this trial was analyzed stratified by tumor burden and the presence or absence of microscopic nonpalpable and palpable regional lymph node metastasis. The benefit of therapy with IFN alpha-2b was greatest among node-positive strata. Toxicity of IFN alpha-2b required dose modification in the majority of patients, but treatment at > or = 80% of the scheduled dose was feasible in the majority of patients through the IV phase of treatment, and for more than 3 months of SC maintenance therapy. Discontinuation of treatment due to toxicity was infrequent after the fourth month of therapy.
  
  
  CONCLUSIONS
  IFN alpha-2b prolongs the relapse-free interval and overall survival of high-risk resected melanoma patients. The increment in median disease-free survival (from 1 to 1.7 years) and overall survival (from 2.8 to 3.8 years) that results from this therapy is associated with a 42% improvement in the fraction of patients who are continuously disease-free after treatment with IFN (from 26% to 37%) in comparison to observation. IFN alpha-2b is the first agent to show a significant benefit in relapse-free and overall survival of high-risk melanoma patients in a randomized controlled trial.
authors.affiliation: Division of Medical Oncology, University of Pittsburgh, PA 15213-2582, USA.
authors.forename: J M
authors.initials: JM
authors.lastname: Kirkwood
authors.forename: M H
authors.initials: MH
authors.lastname: Strawderman
authors.forename: M S
authors.initials: MS
authors.lastname: Ernstoff
authors.forename: T J
authors.initials: TJ
authors.lastname: Smith
authors.forename: E C
authors.initials: EC
authors.lastname: Borden
authors.forename: R H
authors.initials: RH
authors.lastname: Blum
mesh_terms: D056486:Chemical and Drug Induced Liver Injury; D003131:Combined Modality Therapy; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000009:adverse effects / Q000627:therapeutic use*; D008207:Lymphatic Metastasis; D008297:Male; D008545:Melanoma / Q000401:mortality / Q000556:secondary / Q000628:therapy*; D008875:Middle Aged; D015999:Multivariate Analysis; D009364:Neoplasm Recurrence, Local; D009422:Nervous System Diseases / Q000139:chemically induced; D016016:Proportional Hazards Models; D011994:Recombinant Proteins; D012878:Skin Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D016019:Survival Analysis; D015996:Survival Rate
chemical_list: D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins