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Phase II Randomized Study of Vaccine Treatment of Advanced Prostate Cancer (E7897): A Trial of the Eastern Cooperative Oncology Group

From the Columbia University, New York, NY; Dana-Farber Cancer Institute; Beth Israel Deaconess Medical Center, Boston, MA; Cancer Institute of New Jersey, New Brunswick, NJ; Indiana University Medical Center, Indianapolis, IN; University of Pittsburgh, Pittsburgh, PA; National Cancer Institute, Bethesda, MD; University of Wisconsin, Madison, WI; and Fox Chase Cancer Center, Philadelphia, PA

Address reprint requests to Howard Kaufman, MD, Columbia University Medical Center, 177 Fort Washington Avenue, New York, NY 10032; e-mail: hlk2003{at}columbia.edu

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.

This study was conducted by the Eastern Cooperative Oncology Group (Robert L. Comis, MD, Chair) and supported in part by Public Health Service Grants CA23318, CA66636, CA21115, CA14958, CA80775, CA49883, CA39229, CA21076, CA49957, and by the National Cancer Institute, National Institutes of Health and the Department of Health and Human Services. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Cancer Institute.

Preliminary results of this trial were presented at the 38th American Society of Clinical Oncology Annual Meeting, Orlando, FL, May 18–21, 2002.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

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