Team 14 (E. Chatelut): to promote and carry out translational and clinical studies in the field of pharmacology to drive dose individualisation of anticancer drugs
The main objective of our team is to promote and carry out translational and clinical studies in the field of pharmacology to drive dose individualisation of anticancer drugs.
This is made possible by increasing our understanding of the sources of interindividual variability in drug disposition and tumor response. Our main projects focus on pharmacokinetics and pharmacogenetics as interindividual variability factors.
More than 99% of anticancer treatments are prescribed according to standard doses (in mg/m² for cytotoxics or in mg for several targeted therapies). However, a number of observations have shown that interindividual pharmacokinetic (PK) variability contributes to differences between patients both in terms of toxicity and antitumor response. The very limited number of examples of individual dosing in everyday practice in oncology is mainly due to the administration schedule of cytotoxics (i.e. intravenous administration every three weeks). Indeed, these schedules make PK exploration difficult to perform in the first place, as several blood samples are needed in order to determine accurately the area-under-the-curve of drug plasma concentrations versus time (AUC), and secondly the PK results obtained are useless once the administration is over.
Our Unit uses the nonlinear mixed effects approach (commonly known as “population PK”) to improve dose individualisation of anticancer drugs. Our research may be divided into three areas: (i) covariate identification to explain PK variability, (ii) Bayesian approach to determine individual PK parameters from limited blood sampling, and (iii) pharmacokinetic-pharmacodynamic (PK-PD) modeling.
The analytical resources of the lab include Absorption Atomic Spectophotometric, and UPLC-MS-MS systems.
The team is part of PHUC CAPTOR program