title: Inter-patient variability in docetaxel pharmacokinetics: A review.
abstract: Docetaxel is a frequently used chemotherapeutic agent in the treatment of solid cancers. Because of the large inter-individual variability (IIV) in the pharmacokinetics (PK) of docetaxel, it is challenging to determine the optimal dose in individual patients in order to achieve optimal efficacy and acceptable toxicity. Despite the established correlation between systemic docetaxel exposure and efficacy, the precise factors influencing docetaxel PK are not yet completely understood. This review article highlights currently known factors that influence docetaxel PK, and focusses on those that are clinically relevant. For example, liver impairment should be taken into account when calculating docetaxel dosages as this may decrease docetaxel clearance. In addition, drug-drug interactions may be of distinct clinical importance when using docetaxel. Particularly, drugs strongly inhibiting CYP3A4 such as ketoconazole should not be concurrently administered without dose modification, as they may decrease the clearance of docetaxel. Gender, castration status, and menopausal status might be of importance as potential factors influencing docetaxel PK. The role of pharmacogenetics in predicting docetaxel PK is still limited, since no polymorphisms of clinical importance have yet been established.
authors.affiliation: Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands. Electronic address: a.nieuweboer@erasmusmc.nl.
authors.forename: Annemieke J M
authors.initials: AJ
authors.lastname: Nieuweboer
authors.affiliation: Department of Urology, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Ellen S
authors.initials: ES
authors.lastname: de Morrée
authors.affiliation: Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.
authors.forename: Anne-Joy M
authors.initials: AJ
authors.lastname: de Graan
authors.affiliation: Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands; Department of Pharmaceutical Sciences, St Jude Children's Research Hospital, Memphis, TN, United States.
authors.forename: Alex
authors.initials: A
authors.lastname: Sparreboom
authors.affiliation: Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.
authors.forename: Ronald
authors.initials: R
authors.lastname: de Wit
authors.affiliation: Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.
authors.forename: Ron H J
authors.initials: RH
authors.lastname: Mathijssen
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000077143:Docetaxel; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy*; D043823:Taxoids / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D043823:Taxoids; D000077143:Docetaxel
keywords: Docetaxel; Drug-transporters; Drug–drug interactions; Environmental factors; Patient factors; Pharmacokinetics