Docetaxel in hepatic impairment

Purpose. The primary objective of this paper is to provide a brief overview of docetaxel pharmacokinetics, pharmacodynamics, indications, and drug interactions, concentrating on their relationship with docetaxel use in patients with hepatic impairment. Data Sources. The literature was reviewed through a MEDLINE search from 1986 to 2000. Relevant articles cited in literature obtained by MEDLINE searching were also considered. The following terms were searched: hepatic impairment, liver failure, Taxotere, and docetaxel. The search was restricted to the English language. Data Extraction. The current literature is reviewed in regard to docetaxel pharmacokinetics, pharmacodynamics, dosing, efficacy, adverse effects, and drug interactions and with a special emphasis on docetaxel use in patients with hepatic impairment. Data Synthesis. Docetaxel has a wide spectrum of clinical activity and is used frequently in the treatment of metastatic breast cancer, NSCLC, ovarian cancer and cancer of the head and neck. The dose-limiting toxicity of docetaxel is neutropenia. Docetaxel is metabolized in the liver and elevations in hepatic enzymes can predict a reduced clearance of docetaxel, which is associated with an increased incidence of neutropenia. Based on population pharmacokinetic modeling, docetaxel can be safely administered in patients with elevated hepatic enzymes if the dose is reduced on the first cycle.