Phase II randomized study of vaccine treatment of advanced prostate cancer (E7897): a trial of the Eastern Cooperative Oncology Group.
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.
Kaufman
Howard L
HL
Columbia University Medical Center, 177 Fort Washington Avenue, New York, NY 10032, USA. hlk2003@columbia.edu
Wang
Wei
W
Manola
Judith
J
DiPaola
Robert S
RS
Ko
Yoo-Joung
YJ
Sweeney
Christopher
C
Whiteside
Theresa L
TL
Schlom
Jeffrey
J
Wilding
George
G
Weiner
Louis M
LM
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
D019496:Cancer Vaccines; D017430:Prostate-Specific Antigen