Clinical Pharmacokinetics

, Volume 53, Issue 4, pp 305–325

Practical Guidelines for Therapeutic Drug Monitoring of Anticancer Tyrosine Kinase Inhibitors: Focus on the Pharmacokinetic Targets

  • Huixin Yu
  • Neeltje Steeghs
  • Cynthia M. Nijenhuis
  • Jan H. M. Schellens
  • Jos H. Beijnen
  • Alwin D. R. Huitema
Review Article

DOI: 10.1007/s40262-014-0137-2

Cite this article as:
Yu, H., Steeghs, N., Nijenhuis, C.M. et al. Clin Pharmacokinet (2014) 53: 305. doi:10.1007/s40262-014-0137-2

Abstract

There is accumulating evidence for potential benefits of therapeutic drug monitoring (TDM) in the treatment of cancer with tyrosine kinase inhibitors (TKIs). Relationships between exposure and response (efficacy/toxicity) have been established for several TKIs. For example, the pharmacokinetic targets for efficacy of imatinib, sunitinib and pazopanib have been defined as trough plasma concentrations (Ctrough) of >1,000, >50 and >20,000 ng/mL for selected indications, respectively. Dose adjustment based on pharmacokinetic targets could therefore increase response rates and duration. Furthermore, with appropriate target concentrations defined, excessive side effects in patients using the current fixed dosing strategy may be prevented. This review provides a practical guideline for TDM for the currently approved TKIs at 28 February 2013. The focus of this article is on the elaboration of exposure and response relationships of TKIs with proposed pharmacokinetic targets, mainly Ctrough, and further on the interpretation of the pharmacokinetic targets with recommendations for dose titrations.

Copyright information

© Springer International Publishing Switzerland 2014

Authors and Affiliations

  • Huixin Yu
    • 1
  • Neeltje Steeghs
    • 2
    • 3
  • Cynthia M. Nijenhuis
    • 1
  • Jan H. M. Schellens
    • 2
    • 3
    • 4
  • Jos H. Beijnen
    • 1
    • 3
    • 4
  • Alwin D. R. Huitema
    • 1
    • 3
  1. 1.Department of Pharmacy and PharmacologyNetherlands Cancer Institute-Antoni van LeeuwenhoekAmsterdamThe Netherlands
  2. 2.Department of Medical OncologyNetherlands Cancer Institute-Antoni van LeeuwenhoekAmsterdamThe Netherlands
  3. 3.Department of Clinical PharmacologyNetherlands Cancer Institute-Antoni van LeeuwenhoekAmsterdamThe Netherlands
  4. 4.Division of Drug Toxicology, Department of Biomedical Analysis, Faculty of Pharmaceutical SciencesUtrecht UniversityUtrechtThe Netherlands

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