Therapeutic drug monitoring of oral targeted antineoplastic drugs

• Published in: European journal of clinical pharmacology Vol. 77; no. 4; pp. 441 - 464
• Main Authors: Mueller-Schoell, Anna, Groenland, Stefanie L., Scherf-Clavel, Oliver, van Dyk, Madelé, Huisinga, Wilhelm, Michelet, Robin, Jaehde, Ulrich, Steeghs, Neeltje, Huitema, Alwin D.R., Kloft, Charlotte
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.04.2021; Springer Nature B.V
• Subjects: Adverse events; Antineoplastic drugs; Biomedical and Life Sciences; Biomedicine; Dosage; Dose-response effects; Drug dosages; Imatinib; Inhibitor drugs; Pharmacokinetics; Pharmacology/Toxicology; Review; Risk factors; Tamoxifen; Targeted cancer therapy; Therapeutic drug monitoring; Toxicity; Therapeutic drug monitoring; Personalised medicine; Targeted antineoplastic drugs; Oral anticancer drugs; Tyrosine kinase inhibitors
• ISSN: 0031-6970; 1432-1041; 1432-1041
• DOI: 10.1007/s00228-020-03014-8

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.