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
"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.