Fiche publication
Date publication
novembre 2018
Journal
Expert opinion on drug metabolism & toxicology
Auteurs
Membres identifiés du Cancéropôle Est :
Pr BARDOU Marc
,
Pr SCHMITT Antonin
Tous les auteurs :
Goirand F, Lemaitre F, Launay M, Tron C, Chatelut E, Boyer JC, Bardou M, Schmitt A
Lien Pubmed
Résumé
5-FU is currently used as a chemotherapy in several cancers such as head-and-neck (H&N) and colorectal cancers (CRC). 5-FU dosing is traditionally based on body-surface-area, but this strategy is usually associated with severe toxicities. 5-FU is mainly catabolized by dihydropyrimidine dehydrogenase (DPD), and 5-FU dosage adaptation according to DPD status at the first cycle of treatment is now recommended. To further optimize 5-FU-based chemotherapy, a body of evidences justifies therapeutic drug monitoring (TDM). Areas covered: 5-FU Pharmacokinetics, relationships between pharmacokinetics and efficacy or toxicity of 5-FU, proofs of interest of 5-FU TDM and its practical considerations are discussed. Expert opinion: BSA-adjusted 5-FU administration is associated with a large inter-individual variability, and according to this strategy, many patients experience under- or over-exposure. Moreover, relationships between 5-FU area under the curve (AUC) and its toxicity or efficacy have been demonstrated, at least in patients with colorectal or H&N cancers. 5-FU therapeutic index has been validated and algorithms of 5-FU dosage adaptation according to its AUC are now available. Advances in pre-analytical and analytical steps of 5-FU TDM make its use feasible in clinical practice. Thus, there are consistent evidences to recommend 5-FU TDM in patients with advanced colorectal or H&N cancers.
Mots clés
5-fluorouracil, colorectal cancer, head and neck (H&N) cancer, pharmacokinetics, therapeutic drug monitoring (TDM)
Référence
Expert Opin Drug Metab Toxicol. 2018 Nov 19;:
