Drug insight: use of docetaxel in prostate and urothelial cancers

Taxanes have emerged as a potent class of chemotherapeutic agents in many malignancies, with two taxanes now in clinical use. Their mechanism of action against tumor cells is by alteration of microtubule dynamics, which causes cell-cycle arrest during mitosis. Docetaxel binds to the microtubules with a higher affinity than paclitaxel, and over a broader range of cell-cycle activities. It has also been shown to promote apoptosis via BCL2 phosphorylation. In hormone-refractory prostate cancer, docetaxel has been studied as both a single agent and in combination with estramustine, and in different treatment schedules, with demonstrated efficacy. Two phase III trials have confirmed a survival benefit, making docetaxel the first chemotherapy agent with proven efficacy against prostate cancer. In urothelial cancer, docetaxel has demonstrated activity and has been investigated as a single agent and in combination regimens. A phase III trial comparing docetaxel and cisplatin to methotrexate, vinblastine, doxorubicin, and cisplatin was inferior when evaluating response rates and overall survival. More recent phase 11 trials combining docetaxel with two additional agents have shown promise, but confirmatory trials are needed.