title: Phase II randomized study of vaccine treatment of advanced prostate cancer (E7897): a trial of the Eastern Cooperative Oncology Group.
abstract: OBJECTIVE
  A phase II clinical trial was conducted to evaluate the feasibility and tolerability of a prime/boost vaccine strategy using vaccinia virus and fowlpox virus expressing human prostate-specific antigen (PSA) in patients with biochemical progression after local therapy for prostate cancer. The induction of PSA-specific immunity was also evaluated.
  
  
  METHODS
  A randomized clinical trial was conducted by the Eastern Cooperative Oncology group and 64 eligible patients were randomly assigned to receive four vaccinations with fowlpox-PSA (rF-PSA), three rF-PSA vaccines followed by one vaccinia-PSA (rV-PSA) vaccine, or one rV-PSA vaccine followed by three rF-PSA vaccines. The major end point was PSA response at 6 months, and immune monitoring included measurements of anti-PSA and anti-vaccinia antibody titers and PSA-specific T-cell responses.
  
  
  RESULTS
  The prime/boost schedule was well tolerated with few adverse events. Of the eligible patients, 45.3% of men remained free of PSA progression at 19.1 months and 78.1% demonstrated clinical progression-free survival. There was a trend favoring the treatment group that received a priming dose of rV-PSA. Although no significant increases in anti-PSA antibody titers were detected, 46% of patients demonstrated an increase in PSA-reactive T-cells.
  
  
  CONCLUSIONS
  Therapy with poxviruses expressing PSA and delivered in a prime/boost regimen was feasible and associated with minimal toxicity in the cooperative group setting. A significant proportion of men remained free of PSA and clinical progression after 19 months follow-up, and nearly half demonstrated an increase in PSA-specific T-cell responses. Phase III studies are needed to define the role of vaccination in men with prostate cancer or those who are at risk for the disease.
authors.affiliation: Columbia University Medical Center, 177 Fort Washington Avenue, New York, NY 10032, USA. hlk2003@columbia.edu
authors.forename: Howard L
authors.initials: HL
authors.lastname: Kaufman
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Judith
authors.initials: J
authors.lastname: Manola
authors.forename: Robert S
authors.initials: RS
authors.lastname: DiPaola
authors.forename: Yoo-Joung
authors.initials: YJ
authors.lastname: Ko
authors.forename: Christopher
authors.initials: C
authors.lastname: Sweeney
authors.forename: Theresa L
authors.initials: TL
authors.lastname: Whiteside
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Schlom
authors.forename: George
authors.initials: G
authors.lastname: Wilding
authors.forename: Louis M
authors.initials: LM
authors.lastname: Weiner
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D019496:Cancer Vaccines / Q000494:pharmacology / Q000627:therapeutic use*; D018572:Disease-Free Survival; D005240:Feasibility Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality; D014481:United States / Q000453:epidemiology
chemical_list: D019496:Cancer Vaccines; D017430:Prostate-Specific Antigen