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Therapeutic Drug Monitoring of Targeted Anticancer Protein Kinase Inhibitors in Routine Clinical Use: A Critical Review.

PURPOSE
Therapeutic response to oral targeted anticancer protein kinase inhibitors (PKIs) varies widely between patients, with insufficient efficacy of some of them and unacceptable adverse reactions of others. There are several possible causes for this heterogeneity, such as pharmacokinetic variability affecting blood concentrations, fluctuating medication adherence, and constitutional or acquired drug resistance of cancer cells. The appropriate management of oncology patients with PKI treatments thus requires concerted efforts to optimize the utilization of these drug agents, which have probably not yet revealed their full potential.


METHODS
An extensive literature review was performed on MEDLINE on the pharmacokinetics, pharmacodynamics and therapeutic drug monitoring (TDM) of PKIs (up to April 2019).


RESULTS
This article provides the criteria for determining PKIs suitable candidates for TDM (e.g. availability of analytical methods, observational pharmacokinetic studies, PK-PD relationship analysis and randomized controlled studies). It reviews the major characteristics and limitations of PKIs, the expected benefits of TDM for cancer patients receiving them, as well as the prerequisites for the appropriate utilization of TDM. Finally, the paper discusses various important practical aspects and pitfalls of TDM for supporting better implementation in the field of cancer treatment.


CONCLUSION
Adaptation of PKIs dosage regimens at the individual patient level, through a rational TDM approach could prevent oncology patients from being exposed to ineffective or unnecessarily toxic drug concentrations in the era of personalized medicine.