Pharmacology of the taxanes.

The taxanes paclitaxel and docetaxel are structurally similar, but they have different pharmacologic characteristics. Both bind to the beta-subunit of tubulin and affect microtubule polymerization. The cell cycle phases affected by the drugs are distinctly different; paclitaxel inhibits cell cycle traverse at the G2-M phase junction, and docetaxel produces maximum cell killing against cells in S phase. The drugs both undergo hepatic metabolism; however, the specific cytochrome P-450 (CYP) enzymes responsible for hydroxylation are CYP 2C8 for paclitaxel and CYP 3A4 for docetaxel. The cytotoxic effects of the taxanes are schedule dependent. For both drugs, longer durations of exposure increase cytotoxicity. Studies are being conducted to determine if prolonged exposure in cancer cell lines increases response rates in patients with sensitive tumors. The distinct mechanistic and metabolic differences between paclitaxel and docetaxel may influence clinical efficacy and safety in patients with cancer.