Current place of chemotherapy in the treatment of hormone-refractory metastatic prostate cancer.

The current management of hormone-refractory metastatic prostate cancer is purely palliative. The use of chemotherapy in this indication was revised in 1996, based on the results of studies with a combination of mitoxantrone and prednisone. This combination demonstrated a significant improvement of quality of life (+48%) and pain (+30%), but without any overall survival benefit. Two studies using taxols, TAX_ 327 and SWOG_9916, were published in the New England Journal of Medicine on 7 October 2004, with, for the first time, a median overall survival benefit of 2 months. However, the encouraging results of these 2 studies, which will probably modify the management of hormone-refractory prostate cancer, need to be interpreted cautiously. First of all, they were conducted in selected study populations (mean age less than 70 years, Karnofsky index greater than 80% in more than 85% of cases, local disease control in more than 70% of cases). They also comprise many methodological imprecisions and biases with especially, in the TAX_327 study, a change of treatment arm in 1/3 of patients without exclusion of these patients from the final analysis. The results obtained are also at the limit of statistical significance. The target improvement of overall survival, +25% and +33%, respectively, was not achieved at the end of these studies. Finally, from a palliative point of view, only one of these 2 studies (TAX_327) demonstrated a palliative benefit compared to mitoxantrone: 9% for pain, for a sixfold higher cost. Adverse effects were significantly more frequent than with mitoxantrone. Patient selection and details about the indications are necessary. Taxols should not be used systematically in this indication. Furthermore, although several studies are underway, the benefit of taxols at earlier stages of the disease are unknown. Urologists must be aware of the place of chemotherapy in the treatment of prostate cancer in order to remain at the centre of the treatment decision.