Current status and future outlooks on therapeutic drug monitoring of fluorouracil

Expert Opin Drug Metab Toxicol. 2021 Dec;17(12):1407-1422. doi: 10.1080/17425255.2021.2029403. Epub 2022 Jan 24.

Abstract

Introduction: Therapeutic drug monitoring (TDM) of the anticancer drug fluorouracil (5FU) as a method to support dose adjustments has been researched and discussed extensively. Despite manifold evidence of the advantages of 5FU-TDM, traditional body surface area (BSA)-guided dosing is still widely applied.

Areas covered: This review covers the latest evidence on 5FU-TDM based on a literature search in PubMed between June and September 2021. It particularly highlights new approaches of implementing 5FU-TDM into precision medicine by combining TDM with pharmacogenetic testing and/or pharmacometric models. This review further discusses remaining obstacles in order to incorporate 5FU-TDM into clinical routine.

Expert opinion: New data on 5FU-TDM further strengthen the advantages compared to BSA-guided dosing as it is able to reduce pharmacokinetic variability and thereby improve treatment efficacy and safety. Interprofessional collaboration has the potential to overcome the remaining barriers for its implementation. Preemptive pharmacogenetic testing followed by 5FU-TDM can further improve 5FU exposure in a substantial proportion of patients. Developing a model framework integrating pharmacokinetics and pharmacodynamics of 5FU will be crucial to fully advance into the precision medicine era. Model applications can potentially support clinicians in dose finding before starting chemotherapy. Additionally, TDM provides further assistance in continuously improving model predictions.

Keywords: Chemotherapy; fluorouracil; pharmacodynamics; pharmacogenetics; pharmacokinetics; therapeutic drug monitoring.

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents* / adverse effects
  • Body Surface Area
  • Drug Monitoring* / methods
  • Fluorouracil
  • Humans
  • Precision Medicine

Substances

  • Antineoplastic Agents
  • Fluorouracil