Role of chemotherapy in hormone-refractory prostate cancer. Old issues, recent advances and new perspectives.

Prostate cancer that grows despite castrate levels of testosterone and that no longer responds to any form of hormonal manipulation and for which nonhormonal approaches are required, can be precisely defined as hormone-refractory prostate cancer (HRPC). Until recently, there has been no standard chemotherapeutic approach for HRPC. In this article recent advances in the treatment of HRPC using chemotherapeutic regimens are critically reviewed. We performed a MEDLINE search of the published reports from 1995 to 2002 including chemotherapy in the treatment of HRPC. We critically reviewed a total of 84 clinical trials, of which only 6 were phase III trials, most of the studies being phase II trials. Various chemotherapeutic agents have been used. To date, the major benefits of chemotherapy in the treatment of HRPC are palliative in nature, in terms of reduction of pain and use of analgesics and improvement of performance status, as followed in the most recent trials. There is a promising activity of new drug combinations, such as vinca alkaloids and taxanes in association with estramustine. Mitoxantrone, although with a limited activity, has been shown to provide improvement in pain and quality of life for the patients. Several studies suffer from methodological deficits, such as small number of patients, heterogeneity of enrolled groups or no definitive response criteria. Further phase III studies are necessary to better evaluate the efficacy of the different regimens.