Practical guidelines for therapeutic drug monitoring of anticancer tyrosine kinase inhibitors: Focus on the pharmacokinetic targets

Huixin Yu, Neeltje Steeghs, Cynthia M. Nijenhuis, Jan H.M. Schellens, Jos H. Beijnen, Alwin D.R. Huitema

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

199 Citaten (Scopus)

Samenvatting

There is accumulating evidence for potential benefits of therapeutic drug monitoring (TDM) in the treatment of cancer with tyrosine kinase inhibitors (TKIs). Relationships between exposure and response (efficacy/toxicity) have been established for several TKIs. For example, the pharmacokinetic targets for efficacy of imatinib, sunitinib and pazopanib have been defined as trough plasma concentrations (C trough) of >1,000, >50 and >20,000 ng/mL for selected indications, respectively. Dose adjustment based on pharmacokinetic targets could therefore increase response rates and duration. Furthermore, with appropriate target concentrations defined, excessive side effects in patients using the current fixed dosing strategy may be prevented. This review provides a practical guideline for TDM for the currently approved TKIs at 28 February 2013. The focus of this article is on the elaboration of exposure and response relationships of TKIs with proposed pharmacokinetic targets, mainly C trough, and further on the interpretation of the pharmacokinetic targets with recommendations for dose titrations.

Originele taal-2Engels
Pagina's (van-tot)305-325
Aantal pagina's21
TijdschriftClinical Pharmacokinetics
Volume53
Nummer van het tijdschrift4
DOI's
StatusGepubliceerd - apr. 2014
Extern gepubliceerdJa

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