title: Adjuvant low-dose interferon {alpha}2a with or without dacarbazine compared with surgery alone: a prospective-randomized phase III DeCOG trial in melanoma patients with regional lymph node metastasis.
abstract: BACKGROUND
  More than half of patients with melanoma that has spread to regional lymph nodes develop recurrent disease within the first 3 years after surgery. The aim of the study was to improve disease-free survival (DFS) and overall survival (OS) with interferon (IFN) alpha2a with or without dacarbazine (DTIC) compared with observation alone.
  
  
  METHODS
  A total of 444 patients from 42 centers of the German Dermatologic Cooperative Oncology Group who had received a complete lymph node dissection for pathologically proven regional node involvement were randomized to receive either 3 MU s.c. of IFNalpha2a three times a week for 2 years (Arm A) or combined treatment with same doses of IFNalpha2a plus DTIC 850 mg/m(2) every 4-8 weeks for 2 years (Arm B) or to observation alone (Arm C). Treatment was discontinued at first sign of relapse.
  
  
  RESULTS
  A total of 441 patients were eligible for intention-to-treat analysis. Kaplan-Meier 4-year OS rate of those who had received IFNalpha2a was 59%. For those with surgery alone, survival was 42% (A versus C, P = 0.0045). No improvement of survival was found for the combined treatment Arm B with 45% survival rate (B versus C, P = 0.76). Similarly, DFS rates showed significant benefit for Arm A, and not for Arm B. Multivariate Cox model confirmed that Arm A has an impact on OS (P = 0.005) but not Arm B (P = 0.34).
  
  
  CONCLUSIONS
  3 MU interferon alpha2a given s.c. three times a week for 2 years significantly improved OS and DFS in patients with melanoma that had spread to the regional lymph nodes. Interestingly, the addition of DTIC reversed the beneficial effect of adjuvant interferon alpha2a therapy.
authors.affiliation: Division of Dermatologic Oncology, Department of Dermatology, Eberhard-Karls-University of Tübingen, Tübingen, Germany. claus.garbe@med.uni-tuebingen.de
authors.forename: C
authors.initials: C
authors.lastname: Garbe
authors.forename: P
authors.initials: P
authors.lastname: Radny
authors.forename: R
authors.initials: R
authors.lastname: Linse
authors.forename: R
authors.initials: R
authors.lastname: Dummer
authors.forename: R
authors.initials: R
authors.lastname: Gutzmer
authors.forename: J
authors.initials: J
authors.lastname: Ulrich
authors.forename: R
authors.initials: R
authors.lastname: Stadler
authors.forename: M
authors.initials: M
authors.lastname: Weichenthal
authors.forename: Tk
authors.initials: T
authors.lastname: Eigentler
authors.forename: U
authors.initials: U
authors.lastname: Ellwanger
authors.forename: A
authors.initials: A
authors.lastname: Hauschild
mesh_terms: D000293:Adolescent; D000328:Adult; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D002648:Child; D002675:Child, Preschool; D003606:Dacarbazine / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage*; D008197:Lymph Node Excision; D008198:Lymph Nodes / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D008875:Middle Aged; D011446:Prospective Studies; D011788:Quality of Life; D011994:Recombinant Proteins; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D016019:Survival Analysis
chemical_list: D000970:Antineoplastic Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D003606:Dacarbazine