title: Phase III trial comparing adjuvant treatment with pegylated interferon Alfa-2b versus observation: prognostic significance of autoantibodies--EORTC 18991.
abstract: OBJECTIVE
  Conflicting data have been reported concerning the prognostic value of autoimmune antibodies in patients with melanoma treated with adjuvant interferon alfa-2b (IFN). We evaluated the prognostic significance of autoantibodies in the European Organisation for Research and Treatment of Cancer 18991 trial, comparing long-term administration of pegylated IFN (PEG-IFN) with observation.
  
  
  METHODS
  Anticardiolipin, antithyroglobulin, and antinuclear antibodies were determined by enzyme-linked immunosorbent assays in 296 patients before random assignment and every 6 months after random assignment for up to 5 years. Prognostic impact of autoantibodies on recurrence-free survival (RFS) was assessed using the following three Cox models: a model that considered autoantibody appearance as a time-independent variable (model 1); a model that considered a patient to be autoantibody positive from the first positive test (model 2); and a model in which the most recent autoantibody test was used to define the status of the patient (model 3).
  
  
  RESULTS
  Patients who were autoantibody negative at baseline were analyzed (n = 220). Occurrence of autoantibodies during follow-up was higher in the PEG-IFN-treated patients (18% in the observation arm v 52% in the PEG-IFN arm). Autoantibody appearance was of prognostic importance by using model 1 (hazard ratio [HR] = 0.56; 95% CI, 0.36 to 0.87; P = .01). However, when guarantee-time bias was taken into account using model 2 (HR = 1.19; 95% CI, 0.75 to 1.88; P = .46) or method 3 (HR = 1.14; 95% CI, 0.71 to 1.83; P = .59), significance was lost. Results were similar when treatment groups were analyzed separately.
  
  
  CONCLUSIONS
  Appearance of autoimmune antibodies is neither a prognostic nor a predictive factor for improved outcome in patients with melanoma treated with PEG-IFN.
authors.affiliation: Department of Surgery, Division Surgical Oncology, Erasmus University Medical Center-Daniel den Hoed Cancer Center, Rotterdam, the Netherlands.
authors.forename: Marna G
authors.initials: MG
authors.lastname: Bouwhuis
authors.forename: Stefan
authors.initials: S
authors.lastname: Suciu
authors.forename: Alessandro
authors.initials: A
authors.lastname: Testori
authors.forename: Wim H
authors.initials: WH
authors.lastname: Kruit
authors.forename: François
authors.initials: F
authors.lastname: Salès
authors.forename: Poulam
authors.initials: P
authors.lastname: Patel
authors.forename: Cornelis J
authors.initials: CJ
authors.lastname: Punt
authors.forename: Mario
authors.initials: M
authors.lastname: Santinami
authors.forename: Alain
authors.initials: A
authors.lastname: Spatz
authors.forename: Timo L M
authors.initials: TL
authors.lastname: Ten Hagen
authors.forename: Alexander M M
authors.initials: AM
authors.lastname: Eggermont
mesh_terms: D000368:Aged; D017153:Antibodies, Anticardiolipin / Q000097:blood; D000974:Antibodies, Antinuclear / Q000097:blood; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001323:Autoantibodies / Q000097:blood*; D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007279:Injections, Subcutaneous; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000627:therapeutic use*; D053208:Kaplan-Meier Estimate; D008197:Lymph Node Excision; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality / Q000556:secondary / Q000601:surgery; D008875:Middle Aged; D009367:Neoplasm Staging; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000627:therapeutic use*; D016016:Proportional Hazards Models; D011994:Recombinant Proteins; D018570:Risk Assessment; D012307:Risk Factors; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000601:surgery; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D017153:Antibodies, Anticardiolipin; D000974:Antibodies, Antinuclear; D000970:Antineoplastic Agents; D001323:Autoantibodies; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; C006606:anti-thyroglobulin; D011092:Polyethylene Glycols; C417083:peginterferon alfa-2b