ORLANDOA new two-stage prostate cancer vaccine should be explored in a phase III study in metastatic prostate cancer patients, based on promising phase II results of an Eastern Cooperative Oncology Group trial (E7897). Howard L. Kaufman, MD, reported the results of the "prime/boost" vaccine trial at the 38th Annual Meeting of the American Society of Clinical Oncology (ASCO abstract 12).
The vaccine (PROSTVAC, Therion Biologics, Cambridge, Massachusetts) uses a vaccinia-prostate specific antigen (PSA) construct to "prime" the antitumor response, followed by a fowlpox-PSA construct booster to "boost" the immune response.
"We believe now that tumor cells or antigens secreted by tumor cells may be picked up by antigen-presenting cells such as dendritic cells and presented to both CD4 and CD8 T cells, which can then mediate tumor rejection. The vaccine approach largely seeks to enhance or amplify this response," said Dr. Kaufman, associate professor of surgery, Columbia University College of Physicians and Surgeons, New York.
Poxviruses are attractive agents because they replicate in the cytoplasm and do not integrate into the nucleus of infected cells. Infection triggers processing and presentation of the expressed antigens with a full range of immune responses, including antibodies and T-cell-mediated responses. The ECOG trial tested a heterologous prime/boost approach using both vaccinia and nonrepli-cating fowlpox vaccines.
The E7897 study enrolled 70 men with prostate cancer limited to the prostate gland who had completed local therapy at least 3 months prior to randomization. Patients had elevated PSA, defined as greater than 2 ng/mL in surgical patients or as three successive increases for radiation patients. Patients were required to have a negative CT scan of the abdomen and pelvis and a negative bone scan within 4 weeks of randomization. Neo-adjuvant therapy must have been completed 6 months prior to enrollment.
Three Study Arms
Patients were randomized to three study arms. Arm A was a series of four fowlpox PSA vaccinations. Arm B was three fowlpox-PSA injections followed by a single vaccinia-PSA injection. Arm C was a single prime of vaccinia-PSA followed by three fowlpox-PSA immunizations. Patients were vaccinated every 6 weeks. Vaccinia-PSA was given intradermally. Fowlpox-PSA was given subcutaneously. The study was designed with the power to distinguish a 5% PSA progression-free rate at 6 months from a 30% progression-free rate.