Evaluating the utility of therapeutic drug monitoring in the clinical use of small molecule kinase inhibitors: a review of the literature

Research output: Contribution to journalReview articlepeer-review

Abstract

Introduction: Orally administered small molecule kinase inhibitors (KI) are a key class of targeted anti-cancer medicines that have contributed substantially to improved survival outcomes in patients with advanced disease. Since the introduction of KIs in 2001, there has been a building body of evidence that the benefit derived from these drugs may be further enhanced by individualizing dosing on the basis of concentration. Areas covered: This review considers the rationale for individualized KI dosing and the requirements for robust therapeutic drug monitoring (TDM). Current evidence supporting TDM-guided KI dosing is presented and critically evaluated, and finally potential approaches to address translational challenges for TDM-guided KI dosing and alternate approaches to support individualization of KI dosing are discussed. Expert opinion: Intuitively, the individualization of KI dosing through an approach such as TDM-guided dosing has great potential to enhance the effectiveness and tolerability of these drugs. However, based on current literature evidence it is unrealistic to propose that TDM-guided KI dosing should be routinely implemented into clinical practice.

Original languageEnglish
Pages (from-to)803-821
Number of pages19
JournalExpert Opinion on Drug Metabolism and Toxicology
Volume17
Issue number7
DOIs
Publication statusPublished - 2021

Keywords

  • Concentration-guided dosing
  • kinase inhibitors
  • precision medicine
  • therapeutic drug monitoring

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