Currently, approximately 30,000 men die annually of metastatic, hormone-refractory prostate cancer. Androgen blockade is palliative and is generally effective for an average of 2 to 3 years until a patient develops androgen-independent disease. Newer chemotherapeutic regimens can induce remissions in approximately 50% of patients; however, median survival for patients with androgen-independent disease is still 8 to 12 months. The strategy of using chemotherapy regimens after androgen blockade has been proved noncurative, and new approaches are needed to attempt to cure patients with advanced disease. It has been demonstrated in the preclinical setting that androgen withdrawal induces apoptosis in cancer cells in both the Shinogi breast cancer model and the LNCaP prostate cancer model. In both of these models, androgen withdrawal was not curative, and the tumors grew back in a hormone-independent state. It is possible that the addition of chemotherapy at the time of initial androgen ablation will improve cell kill by potentiating apoptosis, thereby killing cells that might otherwise have mutated to the androgen-independent state if allowed to continue to cycle and grow. The rationale behind Radiation Therapy Oncology Group (RTOG) P-0014 is to demonstrate in a randomized phase 3 trial that giving patients chemotherapy at the beginning of androgen blockade may improve patient survival.
ASJC Scopus subject areas