Review of therapeutic drug monitoring of anticancer drugs part two - Targeted therapies.

Details

Serval ID
serval:BIB_54290ACE24ED
Type
Article: article from journal or magazin.
Publication sub-type
Review (review): journal as complete as possible of one specific subject, written based on exhaustive analyses from published work.
Collection
Publications
Institution
Title
Review of therapeutic drug monitoring of anticancer drugs part two - Targeted therapies.
Journal
European Journal of Cancer
Author(s)
Widmer N., Bardin C., Chatelut E., Paci A., Beijnen J., Levêque D., Veal G., Astier A.
ISSN
1879-0852 (Electronic)
ISSN-L
0959-8049
Publication state
Published
Issued date
2014
Peer-reviewed
Oui
Volume
50
Number
12
Pages
2020-2036
Language
english
Notes
Publication types: REVIEWPublication Status: ppublish
Abstract
Most of oral targeted therapies are tyrosine kinase inhibitors (TKIs). Oral administration generates a complex step in the pharmacokinetics (PK) of these drugs. Inter-individual PK variability is often large and variability observed in response is influenced not only by the genetic heterogeneity of drug targets, but also by the pharmacogenetic background of the patient (e.g. cytochome P450 and ABC transporter polymorphisms), patient characteristics such as adherence to treatment and environmental factors (drug-drug interactions). Retrospective studies have shown that targeted drug exposure, reflected in the area under the plasma concentration-time curve (AUC) correlates with treatment response (efficacy/toxicity) in various cancers. Nevertheless levels of evidence for therapeutic drug monitoring (TDM) are however heterogeneous among these agents and TDM is still uncommon for the majority of them. 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/or concerns over adherence treatment. Interpatient PK variability observed with monoclonal antibodies (mAbs) is comparable or slightly lower to that observed with TKIs. There are still few data with these agents in favour of TDM approaches, even if data showed encouraging results with rituximab, cetuximab and bevacizumab. At this time, 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.
Keywords
Monoclonal antibodies, Pharmacokinetics, Protein kinase inhibitors, Target concentration, Targeted therapies, Therapeutic drug monitoring, Tyrosine kinase inhibitors, Variability
Pubmed
Web of science
Create date
13/06/2014 9:19
Last modification date
20/10/2020 9:19
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