Docetaxel, a semisynthetic taxane, has exhibited significant single-agent 
activity against prostatic tumors. In phase I/II studies, single-agent docetaxel 
and the combination of docetaxel plus estramustine were effective in inducing 
prostate-specific antigen reductions of > or =50% in men with 
androgen-independent prostate cancer (AIPC). The underlying reason for 
docetaxel's clinical activity against prostate cancer has been a focus of 
ongoing research. Docetaxel is believed to have a twofold mechanism of 
antineoplastic activity: (1) inhibition of microtubular depolymerization, and 
(2) attenuation of the effects of bcl-2 and bcl-xL gene expression. 
Taxane-induced microtubule stabilization arrests cells in the G(2)M phase of the 
cell cycle and induces bcl-2 phosphorylation, thereby promoting a cascade of 
events that ultimately leads to apoptotic cell death. In preclinical studies, 
docetaxel had a higher affinity for tubulin and was shown to be a more potent 
inducer of bcl-2 phosphorylation than paclitaxel. Laboratory evidence also 
supports the clinical evaluation of docetaxel-based combinations that include 
agents such as trastuzumab and/or estramustine. The pathways for 
docetaxel-induced apoptosis appear to differ in androgen-dependent and 
androgen-independent prostate cancer cells. Further elucidation of these 
differences will be instrumental in designing targeted regimens for the 
treatment of localized and advanced prostate cancer.