Phase II randomized study of vaccine treatment of advanced prostate cancer (E7897): A trial of the Eastern Cooperative Oncology group

Purpose. 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. Patients and 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. Conclusion. 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.