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Review
. 2017 Nov;102(5):765-776.
doi: 10.1002/cpt.787. Epub 2017 Sep 7.

Practical Recommendations for Therapeutic Drug Monitoring of Kinase Inhibitors in Oncology

Remy B Verheijen  1 , Huixin Yu  1 , Jan H M Schellens  2   3 , Jos H Beijnen  1   3 , Neeltje Steeghs  2 , Alwin D R Huitema  1   4
Affiliations
Review

Practical Recommendations for Therapeutic Drug Monitoring of Kinase Inhibitors in Oncology

Remy B Verheijen et al. Clin Pharmacol Ther. 2017 Nov.

Abstract

Despite the fact that pharmacokinetic exposure of kinase inhibitors (KIs) is highly variable and clear relationships exist between exposure and treatment outcomes, fixed dosing is still standard practice. This review aims to summarize the available clinical pharmacokinetic and pharmacodynamic data into practical guidelines for individualized dosing of KIs through therapeutic drug monitoring (TDM). Additionally, we provide an overview of prospective TDM trials and discuss the future steps needed for further implementation of TDM of KIs.

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Figures

Figure 1
Figure 1
Current fixed dosing paradigm (left) vs. the proposed individualized or TDM dosing algorithm (right).
Figure 2
Figure 2
The TDM thresholds of selected KIs as percent of the mean/median exposure of the approved dose (blue bars). Overall, the thresholds were 81.7% of the mean exposure across all agents (orange bar), with a standard deviation of 17.4%. Dotted horizontal lines indicate 100% of mean exposure and 81% (the mean of the thresholds). This analysis suggests that across all kinase inhibitors, the target exposure matches with 81.7% of the population exposure and supports the view that targeting the population average could serve as a proxy, in the absence of a definitive TDM target.
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References

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