Our understanding of the role of chemotherapy for advanced prostate cancer has improved considerably in 2004 with the publication of two large randomized phase III trials and the approval by the US Food and Drug Administration of docetaxel and prednisone for metastatic hormone-refractory disease. Although treatment is still considered palliative in nature, studies of chemotherapy for metastatic hormone-refractory prostate cancer (HRPC) have demonstrated improved overall survival compared with older regimens as well as clinically significant improvements in important endpoints, such as quality of life and time to progression. In particular, docetaxel has emerged as first-line therapy on an every-3-week schedule for metastatic HRPC, replacing mitoxantrone, as recently reported in the TAX327 trial. Docetaxel and estramustine combinations have the disadvantage of significant cardiovascular and gastrointestinal toxicity, and further use of estramustine is likely unwarranted as first-line therapy. Future trials examining novel biologic agents and combination therapies should use single-agent docetaxel as the reference standard. The role of chemotherapy for advanced disease in the neoadjuvant or adjuvant setting, in biochemically (PSA) relapsed patients, and as second-line therapy for relapsed disease, remains a subject of active clinical investigation.
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