In
prostate cancer, there is considerable evidence that
tumors promote immune tolerance starting early in the disease. By suppressing
tumors and activating immune system homeostatic mechanisms,
chemotherapy may help overcome this
tumor-induced immune tolerance. As such,
chemotherapy may therefore support improved results from novel immune-modulating
therapies.
Prostate cancer is particularly suited for active immunotherapy because prostate
tumor cells express a number of distinctive
surface antigens.
Sipuleucel-T, which has recently been approved in the United States, is an active immunotherapy that triggers T-cell responses against
prostate cancer. An exploratory analysis of phase III trial participants found a substantial survival benefit to receiving
docetaxel some months after
sipuleucel-T. However,
VITAL-2, a phase III trial investigating a
prostate cancer therapeutic
vaccine plus concurrent
docetaxel versus standard
docetaxel therapy in advanced
prostate cancer, observed lower overall survival with the
vaccine regimen. This trial highlights major unresolved questions concerning the optimum choice, dosing, and timing of
chemotherapy relative to active immunotherapy. Patient characteristics,
prostate cancer disease stage, and treatment history also may influence the response to combined
therapy. Advances in
biomarker validation and trial design are needed to efficiently investigate these issues.