title: Immunogenicity and antitumor effects of vaccination with peptide vaccine+/-granulocyte-monocyte colony-stimulating factor and/or IFN-alpha2b in advanced metastatic melanoma: Eastern Cooperative Oncology Group Phase II Trial E1696.
abstract: OBJECTIVE
  No therapy has ever shown prolongation of survival in stage IV metastatic melanoma. The association of cytokine-induced autoimmunity with improved prognosis led us to investigate the effect of multi-epitope melanoma vaccines alone and in combination with cytokines in this Eastern Cooperative Oncology Group multicenter phase II trial.
  
  
  METHODS
  Eligible patients were required to have failed prior therapies and to be HLA-A2 positive. Three HLA class I-restricted lineage antigen epitopes were administered in a factorial 2x2 design. Peptide vaccine alone (arm A), or combined with granulocyte-monocyte colony-stimulating factor (GM-CSF; Immunex) 250 microg/d subcutaneously for 14 of 28 days each month (arm B), or combined with IFN-alpha2b (Intron A; Schering-Plough) 10 million units/m2 three times a week (arm C), or combined with both IFN-alpha2b and GM-CSF (arm D). The primary endpoint was immune response measured by enzyme-linked immunospot assay; secondary endpoints were clinical antitumor response, disease-free survival, and overall survival.
  
  
  RESULTS
  One hundred twenty patients enrolled and 115 patients were analyzed. Immune responses to at least one melanoma antigen were observed in 26 of 75 (35%) patients with serial samples. Neither IFN-alpha2b nor GM-CSF significantly improved immune responses. Six objective clinical responses were documented. At a median follow-up of 25.4 months, the median overall survival of patients with vaccine immune response was significantly longer than that of patients with no immune response (21.3 versus 13.4 months; P=0.046).
  
  
  CONCLUSIONS
  Immune response to vaccination correlates with prolonged survival in patients with metastatic melanoma and is not enhanced by immunomodulatory cytokines as tested in this trial.
authors.affiliation: Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania 15213-2584, USA. KirkwoodJM@upmc.edu
authors.forename: John M
authors.initials: JM
authors.lastname: Kirkwood
authors.forename: Sandra
authors.initials: S
authors.lastname: Lee
authors.forename: Stergios J
authors.initials: SJ
authors.lastname: Moschos
authors.forename: Mark R
authors.initials: MR
authors.lastname: Albertini
authors.forename: John C
authors.initials: JC
authors.lastname: Michalak
authors.forename: Cindy
authors.initials: C
authors.lastname: Sander
authors.forename: Theresa
authors.initials: T
authors.lastname: Whiteside
authors.forename: Lisa H
authors.initials: LH
authors.lastname: Butterfield
authors.forename: Louis
authors.initials: L
authors.lastname: Weiner
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019496:Cancer Vaccines / Q000276:immunology*; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality / Q000556:secondary; D008875:Middle Aged; D011994:Recombinant Proteins; D014611:Vaccination
chemical_list: D019496:Cancer Vaccines; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor