Non-hormonal systemic therapies  for the treatment of men with hormone-refractory prostate cancer and clinical evidence of metastases

Our review systematically identified and synthesized the results of 27 clinical trials (n=7489) studying non-hormonal systemic therapy in men with hormone-refractory prostate cancer and metastases and randomizing at least 50 patients per trial.  Twenty trials studied cytotoxic chemotherapy and seven trials noncytotoxic interventions.  The endpoints of interest were overall survival, disease control, palliative response, quality of life, and toxicity.  Trials of second-line hormonal therapies, bisphosphonates or radiopharmaceuticals were not included.
Two trials including 1672 men compared docetaxel-based chemotherapy given every three weeks to mitoxantrone-prednisone and reported improved overall and progression-free survival; pain, quality of life, and PSA response; and similar rates of severe toxicity with the docetaxel regimens.  Docetaxel given weekly provided similar results, but no convincing difference in overall survival was observed and lower grade toxicities were more frequent.  From six trial including 909 men it is unclear whether the addition of estramustine to other cytotoxic agents improves disease control, although increased gastrointestinal and cardiovascular toxicity are reported.  Mitoxantrone and vinorelbine in combination with corticosteroid have been compared to corticosteroid alone in four trials (n=936) have shown improved palliation and disease control.  Thus far trials results of noncytoxic agents such as atrasentan and APC8015 have not convincingly confirmed patient benefits.
 This review suggets that docetaxel-based given every three weeks provides optimal probability of disease control and survival benefit in
men with hormone-refractory prostate cancer and metastases. Mitoxantrone, vinorelbine, and weekly docetaxel have also shown benefits
in disease control and may have a role in selected circumstances.

Bibliographical reference:

Winquist E et al.: "Non-hormonal systemic therapy in men with hormone-refractory prostate cancer and metastases: a systematic review from the Cancer Care Ontario Program in Evidence-based Care's Genitourinary Cancer Disease Site Group", BMC Cancer. 2006 May 2;6(1):112


Eric Winquist
Department of Oncology, University of Western Ontario, London Health Sciences Centre, London, Ontario  Canada