Pharmacogenetic and Pharmacokinetic Dose Individualization of the Taxane Chemotherapeutic Drugs Paclitaxel and Docetaxel

Background: The taxane drugs paclitaxel and docetaxel, widely used on cancer chemotherapy, are currently dosed mainly based on body-surface area. This approach is associated with wide interindividual variability in drug exposure, leading to suboptimal dosing for many patients. Methods: The available evidence supporting dose individualization strategies for paclitaxel and docetaxel were reviewed, focusing mainly on the application of therapeutic drug monitoring by a priori pharmacogenetic data or a posteriori drug measurements in biological fluids. The PubMed database was searched, in the period of 1987-2017, using the keywords pharmacogenetics, metabolic genotyping, dose individualization, therapeutic drug monitoring, personalized medicine, taxanes paclitaxel and docetaxel, either alone or in combination. Results: The current knowledge of pharmacology of the taxane drugs paclitaxel and docetaxel, mainly its pharmacokinetics and the proteins responsible for their biotransformation and transport, along with the genetic polymorphism responsible for variations in the activities of these proteins, opens new opportunities for dose selection for individual patients. Conclusion: Considering the relation between systemic exposure to these drug and clinical responses, a posteriori TDM, with measurement of drug concentrations in plasma of treated patients, is currently the most straightforward approaches for dose individualization of paclitaxel and docetaxel.