E. Chatelut

  Dose individualization of anticancer drugs

 

 

 

 

 

 

 

Our research project at a glance

 

Our team focuses on pharmacokinetics of anticancer drugs in order to better individualize the dose.

 

Objectives

 

The main objective of our team is to promote and carry out translational and clinical studies in the field of pharmacology to drive dose individualization 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 individualization of anticancer drugs.

Our research may be divided into 3 areas:

  • covariate identification to explain PK variability,
  • Bayesian approach to determine individual PK parameters from limited blood sampling,
  • and pharmacokinetic-pharmacodynamic (PK-PD) modeling.

 

Key words

 

  • Population pharmacokinetics
  • Platinum compounds
  • Tyrosine kinase inhibitors
  • Therapeutic drug monitoring
  • PK-PD relationships

 

Labels and networks
Grants and funders

Selected publications


2017

Gandia, P; Jaudet, C; Everaert, H; Heemskerk, J; Vanbinst, A M; de Mey, J; Duerinck, J; Neyns, B; de Ridder, M; Chatelut, E; Concordet, D

Population Pharmacokinetic Approach Applied to Positron Emission Tomography: Computed Tomography for Tumor Tissue Identification in Patients with Glioma Journal Article

Clin Pharmacokinet, 56 (8), pp. 953-961, 2017, ISSN: 1179-1926 (Electronic) 0312-5963 (Linking).

Links | BibTeX

Moeung, S; Chevreau, C; Broutin, S; Guitton, J; Lelievre, B; Ciccolini, J; Massard, C; Flechon, A; Delva, R; Gravis, G; Lotz, J P; Bay, J O; Gross-Goupil, M; Paci, A; Marsili, S; Malard, L; Chatelut, E; Thomas, F

Therapeutic drug monitoring of carboplatin in high-dose protocol (TI-CE) for advanced germ cell tumors: pharmacokinetic results of a phase 2 multicenter study Journal Article

Clin Cancer Res, 2017, ISSN: 1078-0432 (Print) 1078-0432 (Linking).

Links | BibTeX

2016

Imbs, D C; Dieras, V; Bachelot, T; Campone, M; Isambert, N; Joly, F; Jimenez, M; Lafont, T; Chatelut, E

Pharmacokinetic interaction between pazopanib and cisplatin regimen Journal Article

Cancer Chemother Pharmacol, 77 (2), pp. 385-92, 2016, ISSN: 1432-0843 (Electronic) 0344-5704 (Linking).

Links | BibTeX

Sauzay, C; White-Koning, M; Hennebelle, I; Deluche, T; Delmas, C; Imbs, D C; Chatelut, E; Thomas, F

Inhibition of OCT2, MATE1 and MATE2-K as a possible mechanism of drug interaction between pazopanib and cisplatin Journal Article

Pharmacol Res, 110 , pp. 89-95, 2016, ISSN: 1096-1186 (Electronic) 1043-6618 (Linking).

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Thomas, F; Hennebelle, I; Delmas, C; Lochon, I; Dhelens, C; Garnier Tixidre, C; Bonadona, A; Penel, N; Goncalves, A; Delord, J P; Toulas, C; Chatelut, E

Genotyping of a family with a novel deleterious DPYD mutation supports the pretherapeutic screening of DPD deficiency with dihydrouracil/uracil ratio Journal Article

Clin Pharmacol Ther, 99 (2), pp. 235-42, 2016, ISSN: 1532-6535 (Electronic) 0009-9236 (Linking).

Links | BibTeX

2014

Arellano, C; Allal, B; Goubaa, A; Roche, H; Chatelut, E

An UPLC-MS/MS method for separation and accurate quantification of tamoxifen and its metabolites isomers Journal Article

J Pharm Biomed Anal, 100 , pp. 254-261, 2014, ISSN: 1873-264X (Electronic) 0731-7085 (Linking).

Links | BibTeX

Chalret du Rieu, Q; White-Koning, M; Picaud, L; Lochon, I; Marsili, S; Gladieff, L; Chatelut, E; Ferron, G

Population pharmacokinetics of peritoneal, plasma ultrafiltrated and protein-bound oxaliplatin concentrations in patients with disseminated peritoneal cancer after intraperitoneal hyperthermic chemoperfusion of oxaliplatin following cytoreductive surgery: correlation between oxaliplatin exposure and thrombocytopenia Journal Article

Cancer Chemother Pharmacol, 74 (3), pp. 571-82, 2014, ISSN: 1432-0843 (Electronic) 0344-5704 (Linking).

Links | BibTeX

2012

Chatelut, E; White-Koning, M L; Mathijssen, R H; Puisset, F; Baker, S D; Sparreboom, A

Dose banding as an alternative to body surface area-based dosing of chemotherapeutic agents Journal Article

Br J Cancer, 107 (7), pp. 1100-6, 2012, ISSN: 1532-1827 (Electronic) 0007-0920 (Linking).

Links | BibTeX

2011

White-Koning, M; Civade, E; Geoerger, B; Thomas, F; Le Deley, M C; Hennebelle, I; Delord, J P; Chatelut, E; Vassal, G

Population analysis of erlotinib in adults and children reveals pharmacokinetic characteristics as the main factor explaining tolerance particularities in children Journal Article

Clin Cancer Res, 17 (14), pp. 4862-71, 2011, ISSN: 1078-0432 (Print) 1078-0432 (Linking).

Links | BibTeX

2010

Schmitt, A; Gladieff, L; Laffont, C M; Evrard, A; Boyer, J C; Lansiaux, A; Bobin-Dubigeon, C; Etienne-Grimaldi, M C; Boisdron-Celle, M; Mousseau, M; Pinguet, F; Floquet, A; Billaud, E M; Durdux, C; Le Guellec, C; Mazieres, J; Lafont, T; Ollivier, F; Concordet, D; Chatelut, E

Factors for hematopoietic toxicity of carboplatin: refining the targeting of carboplatin systemic exposure Journal Article

J Clin Oncol, 28 (30), pp. 4568-74, 2010, ISSN: 1527-7755 (Electronic) 0732-183X (Linking).

Links | BibTeX