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Drug Discov Today. 2015 Jan;20(1):18-36. doi: 10.1016/j.drudis.2014.09.007. Epub 2014 Sep 22.

Individualized dosing of tyrosine kinase inhibitors: are we there yet?

Author information

1
Department of Clinical Pharmacy & Toxicology, Leiden University Medical Center, Leiden, The Netherlands.
2
Department of Clinical Pharmacy & Toxicology, Leiden University Medical Center, Leiden, The Netherlands. Electronic address: H.J.Guchelaar@lumc.nl.
3
Department of Clinical Oncology, Leiden University Medical Center, Leiden, The Netherlands.
4
Department of Clinical Pharmacy, Radboud University Medical Center, Nijmegen, The Netherlands.

Abstract

Tyrosine kinase inhibitors (TKIs) are registered at a fixed oral dose, despite their large variability in pharmacokinetics (PK). Given that the evidence for a relation between drug exposure and treatment outcome is growing, this one-dose-fits-all approach can unintentionally lead to under- and overexposure. Dose individualization could lower this variability and thereby beneficially effect treatment outcome. In this article, we explore whether TKIs used for solid tumors meet the criteria for dose individualization. Despite limitations such as retrospective analysis, current data suggest that the following Ctrough levels could be used: imatinib 1100ng/ml, sunitinib when continuously dosed 37.5ng/ml, intermittent 50ng/ml and pazopanib 20μg/ml. A comprehensive review of the literature also shows that prospective trials investigating the influence of dose individualization on treatment outcome are warranted.

PMID:
25245169
DOI:
10.1016/j.drudis.2014.09.007
[Indexed for MEDLINE]

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