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Individualized dosing of oral targeted therapies in oncology is crucial in the era of precision medicine

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Abstract

Purpose

While in the era of precision medicine, the right drug for each patient is selected based on molecular tumor characteristics, most novel oral targeted anticancer agents are still being administered using a one-size-fits-all fixed dosing approach. In this review, we discuss the scientific evidence for dose individualization of oral targeted therapies in oncology, based on therapeutic drug monitoring (TDM).

Methods

Based on literature search and our own experiences, seven criteria for drugs to be suitable candidates for TDM will be addressed: (1) absence of an easily measurable biomarker for drug effect; (2) long-term therapy; (3) availability of a validated sensitive bioanalytical method; (4) significant variability in pharmacokinetic exposure; (5) narrow therapeutic range; (6) defined and consistent exposure-response relationships; (7) feasible dose-adaptation strategies.

Results

All of these requirements are met for most oral targeted therapies in oncology. Also, prospective studies have already shown TDM to be feasible for imatinib, pazopanib, sunitinib, everolimus, and endoxifen.

Conclusions

In order to realize the full potential of personalized medicine in oncology, patients should not only be treated with the right drug, but also at the right dose. TDM could be a suitable tool to achieve this.

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Authors and Affiliations

  1. Department of Clinical Pharmacology, Division of Medical Oncology, The Netherlands Cancer Institute – Antoni van Leeuwenhoek, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands

    Stefanie L. Groenland & Neeltje Steeghs

  2. Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands

    Ron H. J. Mathijssen

  3. Department of Pharmacy & Pharmacology, The Netherlands Cancer Institute – Antoni van Leeuwenhoek, Amsterdam, The Netherlands

    Jos H. Beijnen & Alwin D. R. Huitema

  4. Department of Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands

    Jos H. Beijnen

  5. Department of Clinical Pharmacy, University Medical Center, Utrecht University, Utrecht, The Netherlands

    Alwin D. R. Huitema

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  1. Stefanie L. Groenland
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  2. Ron H. J. Mathijssen
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  3. Jos H. Beijnen
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  4. Alwin D. R. Huitema
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  5. Neeltje Steeghs
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Conception and design of this review were performed by SG, AH, and NS; SG wrote the manuscript; RM, JB, AH, and NS critically reviewed the manuscript.

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Correspondence to Stefanie L. Groenland.

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Groenland, S.L., Mathijssen, R.H.J., Beijnen, J.H. et al. Individualized dosing of oral targeted therapies in oncology is crucial in the era of precision medicine. Eur J Clin Pharmacol 75, 1309–1318 (2019). https://doi.org/10.1007/s00228-019-02704-2

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  • DOI: https://doi.org/10.1007/s00228-019-02704-2

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