Therapeutic drug monitoring in cancer - Are we missing a trick?

Détails

ID Serval
serval:BIB_AC014008E73C
Type
Article: article d'un périodique ou d'un magazine.
Sous-type
Editorial
Collection
Publications
Titre
Therapeutic drug monitoring in cancer - Are we missing a trick?
Périodique
European Journal of Cancer
Auteur(s)
Bardin C., Veal G., Paci A., Chatelut E., Astier A., Levêque D., Widmer N., Beijnen J.
ISSN
1879-0852 (Electronic)
ISSN-L
0959-8049
Statut éditorial
Publié
Date de publication
2014
Peer-reviewed
Oui
Volume
50
Numéro
12
Pages
2005-2009
Langue
anglais
Notes
Publication types: Journal Article Publication Status: ppublish. pdf type: Position Paper
Résumé
Therapeutic drug monitoring (TDM) can be defined as the measurement of drug in biological samples to individualise treatment by adapting drug dose to improve efficacy and/or reduce toxicity. The cytotoxic drugs are characterised by steep dose-response relationships and narrow therapeutic windows. Inter-individual pharmacokinetic (PK) variability is often substantial. There are, however, a multitude of reasons why TDM has never been fully implemented in daily oncology practice. These include difficulties in establishing appropriate concentration target, common use of combination chemotherapies and the paucity of published data from pharmacological trials. The situation is different with targeted therapies. The large interindividual PK variability is influenced by the pharmacogenetic background of the patient (e.g. cytochrome P450 and ABC transporters polymorphisms), patient characteristics such as adherence to treatment and environmental factors (drug-drug interactions). Retrospective studies have shown that targeted drug exposure correlates with treatment response in various cancers. Evidence for imatinib currently exists, others are emerging for compounds including nilotinib, dasatinib, erlotinib, sunitinib, sorafenib and mammalian target of rapamycin (mTOR) inhibitors. Applications for TDM during oral targeted therapies may best be reserved for particular situations including lack of therapeutic response, severe or unexpected toxicities, anticipated drug-drug interactions and concerns over adherence treatment. There are still few data with monoclonal antibodies (mAbs) in favour of TDM approaches, even if data showed encouraging results with rituximab and cetuximab. TDM of mAbs is not yet supported by scientific evidence. Considerable effort should be made for targeted therapies to better define concentration-effect relationships and to perform comparative randomised trials of classic dosing versus pharmacokinetically-guided adaptive dosing.
Mots-clé
Chemotherapy, Cytotoxics, Monoclonal antibodies, Oncology, Pharmacokinetics, Target concentration, Targeted therapies, Therapeutic drug monitoring, Tyrosine kinase inhibitors, Variability
Pubmed
Web of science
Création de la notice
07/06/2014 21:59
Dernière modification de la notice
20/08/2019 15:16
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