The evolving role of chemotherapy in androgen-independent (hormone-refractory) prostate cancer.

Over the last decade, much progress has been made in the treatment of advanced hormone-refractory prostate cancer (HRPC). The mitoxantrone-prednisone drug combination was approved in the United States based on palliative end points and became the standard of care despite the lack of survival benefit. Docetaxel demonstrated clinical activity in HRPC on weekly and every-3-weeks schedules as evidenced by decreases in prostate-specific antigen (PSA) values that were higher than those traditionally seen with other chemotherapy regimens. The TAX 327 phase 3 trial was designed to further define the role of docetaxel in HRPC. A total of 1006 patients were randomized to receive docetaxel 75 mg/m2 every 3 weeks, docetaxel 30 mg/m2 weekly for 5 of 6 weeks, or mitoxantrone 12 mg/m2 every 3 weeks. All patients received daily prednisone. The primary study objective was survival, with secondary objectives of pain response, PSA decrease, measurable response, and quality of life (QOL). Compared with mitoxantrone, a survival benefit was demonstrated for docetaxel every 3 weeks (P = 0.009) and for the combined docetaxel arms (P = 0.03, respectively). Decreases in PSA values were superior with docetaxel (45% for the every-3-weeks regimen, P = 0.0005; 47% for the weekly regimen, P < 0.0001). Pain improvement was superior in the every-3-weeks docetaxel arm (P = 0.0107), and QOL was significantly better with both docetaxel regimens (every 3 weeks, P = 0.009; weekly, P = 0.005). Serious toxicity was rare in all arms. Given these compelling results, it can be concluded that docetaxel represents a new standard of care for the treatment of HRPC.