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Review
. 2021 Apr;77(4):441-464.
doi: 10.1007/s00228-020-03014-8. Epub 2020 Nov 9.

Therapeutic drug monitoring of oral targeted antineoplastic drugs

Anna Mueller-Schoell  1   2 , Stefanie L Groenland  3 , Oliver Scherf-Clavel  4 , Madelé van Dyk  5 , Wilhelm Huisinga  6 , Robin Michelet  1 , Ulrich Jaehde  7 , Neeltje Steeghs  3 , Alwin D R Huitema  8   9 , Charlotte Kloft  10
Affiliations
Review

Therapeutic drug monitoring of oral targeted antineoplastic drugs

Anna Mueller-Schoell et al. Eur J Clin Pharmacol. 2021 Apr.

Erratum in

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.

Keywords: Oral anticancer drugs; Personalised medicine; Targeted antineoplastic drugs; Therapeutic drug monitoring; Tyrosine kinase inhibitors.

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Conflict of interest statement

CK and WH report grants from an industry consortium (AbbVie Deutschland GmbH & Co. KG, Astra Zeneca, Boehringer Ingelheim Pharma GmbH & Co. KG, Grünenthal GmbH, F. Hoffmann-La Roche Ltd., Merck KGaA and Sanofi) for the PharMetrX PhD program. CK reports grant for the Innovative Medicines Initiative-Joint Undertaking (‘DDMoRe’). CK and RM report grants from the Federal Ministry of Education and Research within the Joint Programming Initiative on Antimicrobial Resistance Initiative (JPIAMR), all outside the submitted work. OS reports endowed professorship grant (Horphag research Ltd) and funding for the project ‘Individualized cancer therapy with kinase inhibitors using drug monitoring – optimization by minimally invasive at-home sampling’ (Hector Stiftung II gGmbH). The remaining authors declare that the research was conducted in absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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