[Focus on cellular pharmacology of docetaxel]

Docetaxel, a member of the taxoid class of antineoplasic agents, is derived from an inactive precursor obtained from the needles of the European yew. Docetaxel is characterised by a wide spectrum of in vitro cytotoxicity an murine and human tumour cell lines and in vivo antitumour activity against human tumour xenografted in athymic mice. The principal mechanism by which docetaxel exerts its cytotoxic activity is through enhancement and stabilisation of microtubule assembly leading to an arrest of the cell cycle at the G2/M phase. It has also been shown to induce tumour cell death by apoptosis and to have antiangiogenic and immunostimulating properties. Docetaxel demonstrated in vitro and/or in vivo additive and synergistic effects when combined with a large spectrum of anticancer therapies such as new cytotoxic agents (gemcitabine, capecitabine, edatrexate), specific signal transduction drugs, Herceptin, antiangiogenic drugs, gene therapy, or antisense olignonucleotides, opening to new treatment strategies. Despite close chemical structures, preclinical data suggested a difference in the cellular pharmacology of docetaxel and paclitaxel leading to different profiles in clinical studies.