Major pitfalls of protein kinase inhibitors prescription: A review of their clinical pharmacology for daily use

Crit Rev Oncol Hematol. 2019 Sep:141:112-124. doi: 10.1016/j.critrevonc.2019.06.006. Epub 2019 Jun 16.

Abstract

Protein kinase inhibitors (PKI) are a growing class of anticancer agents. They are prescribed with flat doses, and their oral administration is associated with interindividual variability in exposure. Patients can be over- or underexposed, due to numerous factors. We reviewed key pharmacokinetic concepts and mechanisms by which PKIs prescription could be altered. Challenging situations that could lead to increased toxicity or to therapeutic failure are described and recommendation for clinicians are proposed. Finally, the interest of therapeutic drug monitoring and indications for its use in daily practice is discussed.

Keywords: Cancer treatment; Pharmacology; Protein kinase inhibitors; Therapeutic drug monitoring.

Publication types

  • Review

MeSH terms

  • Area Under Curve
  • Biomarkers, Pharmacological / analysis
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Drug Monitoring / methods
  • Humans
  • Inactivation, Metabolic / physiology
  • Pharmacology, Clinical
  • Practice Patterns, Physicians' / standards*
  • Practice Patterns, Physicians' / statistics & numerical data
  • Protein Kinase Inhibitors / pharmacokinetics*
  • Protein Kinase Inhibitors / pharmacology
  • Protein Kinase Inhibitors / therapeutic use*
  • Tissue Distribution

Substances

  • Biomarkers, Pharmacological
  • Protein Kinase Inhibitors