title: Adjuvant immunotherapy of resected, intermediate-thickness, node-negative melanoma with an allogeneic tumor vaccine: overall results of a randomized trial of the Southwest Oncology Group.
abstract: OBJECTIVE
  Patients with clinically negative nodes constitute over 85% of new melanoma cases. There is no adjuvant therapy for intermediate-thickness, node-negative melanoma patients.
  
  
  METHODS
  The Southwest Oncology Group conducted a randomized phase III trial of an allogeneic melanoma vaccine for 2 years versus observation in patients with intermediate-thickness (1.5 to 4.0 mm or Clark's level IV if thickness unknown), clinically or pathologically node-negative melanoma (T3N0M0).
  
  
  RESULTS
  Six hundred eighty-nine patients were accrued over 4.5 years; 89 patients (13%) were ineligible. Surgical node staging was performed in 24%, the remainder were clinical N0. Thirteen eligible patients refused assigned treatment: seven on the observation arm and six on the vaccine arm. Most vaccine patients experienced mild to moderate local toxicity, but 26 (9%) experienced grade 3 toxicity. After a median follow-up of 5.6 years, there were 107 events (tumor recurrences or deaths) among the 300 eligible patients randomized to vaccine compared with 114 among the 300 eligible patients randomized to observation (hazard ratio, 0.92; Cox-adjusted P(2) = 0.51). There was no difference in vaccine efficacy among patients with tumors < or = 3 mm or > 3 mm.
  
  
  CONCLUSIONS
  This represents one of the largest randomized, controlled trials of adjuvant vaccine therapy in human cancer reported to date. Compliance with randomization was excellent, with only 2% refusing assigned therapy. There is no evidence of improved disease-free survival among patients randomized to receive vaccine, although the power to detect a small but clinically significant difference was low. Future investigations of adjuvant vaccine approaches for patients with intermediate-thickness melanoma should involve larger numbers of patients and ideally should include sentinel node biopsy staging.
authors.affiliation: University of Michigan Comprehensive Cancer Center, Ann Arbor, USA.
authors.forename: Vernon K
authors.initials: VK
authors.lastname: Sondak
authors.forename: P-Y
authors.initials: PY
authors.lastname: Liu
authors.forename: Ralph J
authors.initials: RJ
authors.lastname: Tuthill
authors.forename: Raymond A
authors.initials: RA
authors.lastname: Kempf
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Unger
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Sosman
authors.forename: John A
authors.initials: JA
authors.lastname: Thompson
authors.forename: Geoffrey R
authors.initials: GR
authors.lastname: Weiss
authors.forename: Bruce G
authors.initials: BG
authors.lastname: Redman
authors.forename: James G
authors.initials: JG
authors.lastname: Jakowatz
authors.forename: R Dirk
authors.initials: RD
authors.lastname: Noyes
authors.forename: Lawrence E
authors.initials: LE
authors.lastname: Flaherty
mesh_terms: D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019496:Cancer Vaccines / Q000627:therapeutic use*; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008545:Melanoma / Q000473:pathology / Q000601:surgery / Q000628:therapy*; D008875:Middle Aged; D016016:Proportional Hazards Models
chemical_list: D000276:Adjuvants, Immunologic; D019496:Cancer Vaccines; C116434:Melacine