LiverTox: Clinical and Research Information on Drug-Induced Liver Injury

The taxanes or taxoids are a closely related group of antineoplastic agents that have a unique mechanism of action as inhibitors of mitosis and which are widely used in the therapy of ovarian, breast, lung, esophageal, prostate, bladder and head and neck cancers. Three taxanes are in clinical use, paclitaxel (Taxol: 1992), docetaxel (Taxotere: 1996) and cabazitaxel (Jevtana: 2010). Paclitaxel was the first compound in this chemical group to be introducted into clinical use and was initially isolated from the bark of the Western yew tree. Docetaxel is a semisynthetic analogue of paclitaxel and a derivative of extracts from needles of the European Yew (Taxus baccata) that has somewhat better pharmacokinetics and different side effects than paclitaxel. Cabazitaxel is also a semisynthetic analogue of natural taxoids and was developed for its lack of affinity for P-glycoprotein, a common mediator of docetaxel reistance. The taxanes are similar to the vinca alkaloids in that they bind to tubulin and cause inhibition of mitosis. However, the taxanes bind at a different site than the vinca alkaloids and cause inhibition of mitosis by prevention of degradation of microtubules, rather than prevention of their assembly. Three three taxanes are all given intravenously, usually every 1 to 3 weeks. While taxanes have many side effects and can be associated with serum enzyme elevations during treatment, they have not been linked to idiosyncratic, clinically apparent liver injury with jaundice. The few case reports of acute liver injury associated with taxanes (largely docetaxel) have occurred in patients with acute hypersensitivity reactions, sepsis or multiorgan failure. The taxanes are discussed separately, but general references to their hepatotoxicity and safety are given at the end of this Overview section. Drug Class: Antineoplastic Agents