Drug-drug interactions in breast cancer patients treated with CDK4/6 inhibitors

Cancer Treat Rev. 2019 Mar:74:21-28. doi: 10.1016/j.ctrv.2019.01.006. Epub 2019 Jan 19.

Abstract

CDK4/6 inhibitors are a new class of anticancer drugs used for the treatment of women with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced or metastatic breast cancer with disease progression following endocrine therapy. Polypharmacy is a well-known problem in advanced cancer causing potential drug-drug interactions (DDIs), which, in turn, may limit the therapeutic value of CDK4/6 inhibitors. Therefore, understanding the mechanisms underlying potential DDIs in patients taking CDK4/6 inhibitors may be useful in decision-making processes and represent an important step towards treatment personalization. The present review is aimed at describing the potential DDIs that might occur in breast cancer patients receiving CDK4/6 inhibitors based on direct evidence from the literature and mechanistic considerations tailored on specific class of drugs used in combination.

Keywords: Breast cancer; CDK4/6 inhibitors; Drug-drug interaction; Pharmacodynamics; Pharmacokinetics; Treatment personalization.

Publication types

  • Review

MeSH terms

  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / enzymology
  • Breast Neoplasms / metabolism
  • Cyclin-Dependent Kinase 4 / antagonists & inhibitors*
  • Cyclin-Dependent Kinase 4 / metabolism
  • Cyclin-Dependent Kinase 6 / antagonists & inhibitors*
  • Cyclin-Dependent Kinase 6 / metabolism
  • Drug Interactions
  • Humans
  • Protein Kinase Inhibitors / administration & dosage
  • Protein Kinase Inhibitors / pharmacokinetics
  • Protein Kinase Inhibitors / pharmacology*

Substances

  • Protein Kinase Inhibitors
  • CDK4 protein, human
  • CDK6 protein, human
  • Cyclin-Dependent Kinase 4
  • Cyclin-Dependent Kinase 6