How can we best monitor 5-FU administration to maximize benefit to risk ratio?

Abstract : 5-FU is currently used as a chemotherapy in several cancers such as head-and-neck (HandN) 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 HandN 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 HandN cancers.
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Françoise Goirand, Florian Lemaitre, Manon Launay, Camille Tron, Etienne Chatelut, et al.. How can we best monitor 5-FU administration to maximize benefit to risk ratio?. Expert Opinion on Drug Metabolism and Toxicology, Taylor & Francis, 2018, 14 (12), pp.1303-1313. ⟨10.1080/17425255.2018.1550484⟩. ⟨hal-01936325⟩

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