Therapeutic drug monitoring of oral targeted antineoplastic drugs

Anna Mueller-Schoell, Stefanie L. Groenland, Oliver Scherf-Clavel, Madelé van Dyk, Wilhelm Huisinga, Robin Michelet, Ulrich Jaehde, Neeltje Steeghs, Alwin D.R. Huitema, Charlotte Kloft

Research output: Contribution to journalReview articlepeer-review

18 Citations (Scopus)
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Abstract

Purpose: This review provides an overview of the current challenges in oral targeted antineoplastic drug (OAD) dosing and outlines the unexploited value of therapeutic drug monitoring (TDM). Factors influencing the pharmacokinetic exposure in OAD therapy are depicted together with an overview of different TDM approaches. Finally, current evidence for TDM for all approved OADs is reviewed. Methods: A comprehensive literature search (covering literature published until April 2020), including primary and secondary scientific literature on pharmacokinetics and dose individualisation strategies for OADs, together with US FDA Clinical Pharmacology and Biopharmaceutics Reviews and the Committee for Medicinal Products for Human Use European Public Assessment Reports was conducted. Results: OADs are highly potent drugs, which have substantially changed treatment options for cancer patients. Nevertheless, high pharmacokinetic variability and low treatment adherence are risk factors for treatment failure. TDM is a powerful tool to individualise drug dosing, ensure drug concentrations within the therapeutic window and increase treatment success rates. After reviewing the literature for 71 approved OADs, we show that exposure-response and/or exposure-toxicity relationships have been established for the majority. Moreover, TDM has been proven to be feasible for individualised dosing of abiraterone, everolimus, imatinib, pazopanib, sunitinib and tamoxifen in prospective studies. There is a lack of experience in how to best implement TDM as part of clinical routine in OAD cancer therapy. Conclusion: Sub-therapeutic concentrations and severe adverse events are current challenges in OAD treatment, which can both be addressed by the application of TDM-guided dosing, ensuring concentrations within the therapeutic window.

Original languageEnglish
Pages (from-to)441-464
Number of pages24
JournalEuropean Journal of Clinical Pharmacology
Volume77
Issue number4
Early online date9 Nov 2020
DOIs
Publication statusPublished - Apr 2021

Keywords

  • Oral anticancer drugs
  • Personalised medicine
  • Targeted antineoplastic drugs
  • Therapeutic drug monitoring
  • Tyrosine kinase inhibitors

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