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

  • Stefanie L. GroenlandEmail author
  • Ron H. J. Mathijssen
  • Jos H. Beijnen
  • Alwin D. R. Huitema
  • Neeltje Steeghs
Point of View

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.

Keywords

Therapeutic drug monitoring Individualized dosing Personalized medicine Precision medicine Oral targeted therapies 

Notes

Author’s contributions

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.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Stefanie L. Groenland
    • 1
    Email author
  • Ron H. J. Mathijssen
    • 2
  • Jos H. Beijnen
    • 3
    • 4
  • Alwin D. R. Huitema
    • 3
    • 5
  • Neeltje Steeghs
    • 1
  1. 1.Department of Clinical Pharmacology, Division of Medical OncologyThe Netherlands Cancer Institute – Antoni van LeeuwenhoekAmsterdamThe Netherlands
  2. 2.Department of Medical OncologyErasmus MC Cancer InstituteRotterdamThe Netherlands
  3. 3.Department of Pharmacy & PharmacologyThe Netherlands Cancer Institute – Antoni van LeeuwenhoekAmsterdamThe Netherlands
  4. 4.Department of Pharmaceutical SciencesUtrecht UniversityUtrechtThe Netherlands
  5. 5.Department of Clinical PharmacyUniversity Medical Center, Utrecht UniversityUtrechtThe Netherlands

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