New Hope for Patients with Metastatic Hormone-Refractory Prostate Cancer

Traditionally, chemotherapeutic agents were viewed as having little or no impact on the natural history of hormone-refractory prostate cancer (HRPC). For many years, patients with HRPC could be offered only palliative treatments and accordingly their prognosis was poor. Recently, two proof-of-concept studies revealed that prostate-specific antigen (PSA) responses can be detected in 38-46% of patients treated with docetaxel every 3 weeks (q3w) and, more importantly, measurable objective responses are also reported in 24-29% of patients. These findings prompted the initiation of two phase 3 trials, TAX 327 and SWOG-99-16, which compared docetaxel-based chemotherapy with the standard combination treatment of mitoxantrone and prednisone and were designed to test for an improvement in survival. The findings of the TAX 327 and SWOG-99-16 studies challenge the belief that HRPC is a chemotherapy-resistant disease, and reveal that q3w docetaxel plus prednisone is well tolerated and offers superior survival and improved patient quality of life compared with the former standard treatment of mitoxantrone and prednisone. This opens up a number of new directions for our clinical investigations. Not only is docetaxel now being evaluated in patients with earlier stage prostate cancer, for whom chemotherapy may offer better long-term outcomes by decreasing the risk of systemic relapse, but combinations of novel chemotherapeutic agents with docetaxel are also being investigated and may well offer further benefits to patients with HRPC.