Overcoming barriers to implementing precision dosing with 5-fluorouracil and capecitabine

Br J Clin Pharmacol. 2021 Feb;87(2):317-325. doi: 10.1111/bcp.14723. Epub 2021 Jan 15.

Abstract

Despite advances in targeted cancer therapy, the fluoropyrimidines 5-fluorouracil (5FU) and capecitabine continue to play an important role in oncology. Historically, dosing of these drugs has been based on body surface area. This approach has been demonstrated to be an imprecise way to determine the optimal dose for a patient. Evidence in the literature has demonstrated that precision dosing approaches, such as DPD enzyme activity testing and, in the case of intravenous 5FU, pharmacokinetic-guided dosing, can reduce toxicity and yield better patient outcomes. However, despite the evidence, there has not been uniform adoption of these approaches in the clinical setting. When a drug such as 5FU has been used clinically for many decades, it may be difficult to change clinical practice. With the aim of facilitating change of practice, issues and barriers to implementing precision dosing approaches for 5FU and capecitabine are identified and discussed with possible solutions proposed.

Keywords: 5-fluorouracil; capecitabine; pharmacokinetics; therapeutic drug monitoring.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antimetabolites, Antineoplastic / adverse effects
  • Capecitabine / adverse effects
  • Fluorouracil* / adverse effects
  • Humans
  • Neoplasms* / drug therapy

Substances

  • Antimetabolites, Antineoplastic
  • Capecitabine
  • Fluorouracil