Review of therapeutic drug monitoring of anticancer drugs part 1--cytotoxics.

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State: Public
Version: Final published version
Serval ID
serval:BIB_AC49836EB0F2
Type
Article: article from journal or magazin.
Collection
Publications
Title
Review of therapeutic drug monitoring of anticancer drugs part 1--cytotoxics.
Journal
European Journal of Cancer (oxford, England : 1990)
Author(s)
Paci A., Veal G., Bardin C., Levêque D., Widmer N., Beijnen J., Astier A., Chatelut E.
ISSN
1879-0852 (Electronic)
ISSN-L
0959-8049
Publication state
Published
Issued date
2014
Volume
50
Number
12
Pages
2010-2019
Language
english
Notes
Publication types: Journal Article ; Review
Publication Status: ppublish
Abstract
Most anticancer drugs are characterised by a steep dose-response relationship and narrow therapeutic window. Inter-individual pharmacokinetic (PK) variability is often substantial. The most relevant PK parameter for cytotoxic drugs is the area under the plasma concentration versus time curve (AUC). Thus it is somewhat surprising that therapeutic drug monitoring (TDM) is still uncommon for the majority of agents. Goals of the review were to assess the rationale for more widely used TDM of cytotoxics in oncology. There are several reasons why TDM has never been fully implemented into daily oncology practice. These include difficulties in establishing appropriate concentration target ranges, common use of combination chemotherapies for many tumour types, analytical challenges with prodrugs, intracellular compounds, the paucity of published data from pharmacological trials and 'Day1 = Day21' administration schedules. There are some specific situations for which these limitations are overcome, including high dose methotrexate, 5-fluorouracil infusion, mitotane and some high dose chemotherapy regimens. TDM in paediatric oncology represents an important challenge. Established TDM approaches includes the widely used anticancer agents carboplatin, busulfan and methotrexate, with 13-cis-retinoic acid also recently of interest. Considerable effort should be made to better define concentration-effect relationships and to utilise tools such as population PK/PD models and comparative randomised trials of classic dosing versus pharmacokinetically guided adaptive dosing. There is an important heterogeneity among clinical practices and a strong need to promote TDM guidelines among the oncological community.
Keywords
Antineoplastic Agents/pharmacokinetics, Antineoplastic Agents/toxicity, Antineoplastic Combined Chemotherapy Protocols/pharmacokinetics, Antineoplastic Combined Chemotherapy Protocols/toxicity, Clinical Trials as Topic, Cytotoxins/pharmacokinetics, Dose-Response Relationship, Drug, Drug Monitoring/methods, Humans, Neoplasms/drug therapy
Pubmed
Create date
12/02/2015 11:15
Last modification date
20/08/2019 16:16
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