Title:Pharmacogenetic and Pharmacokinetic Dose Individualization of the Taxane Chemotherapeutic Drugs Paclitaxel and Docetaxel
Volume: 24
Issue: 33
Author(s): Natalia B. Andriguetti , Suziane Raymundo, Marina V. Antunes, Magda S. Perassolo, Simone G. Verza, Edna S. Suyenaga and Rafael Linden*
Affiliation:
- Laboratory of Analytical Toxicology, Institute of Health Sciences, Universidade Feevale, Novo Hamburgo-RS,Brazil
Keywords:
Pharmacogenetics, metabolic genotyping, dose individualization, therapeutic drug monitoring, personalized
medicine, taxanes paclitaxel, docetaxel.
Abstract: 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.
