AACR is hosting a workshop with the FDA on January 16, 2025, to discuss the considerations for routine testing of DPD deficiency before treatment with fluoropyrimidines.

Although the updated CPIC guideline for DPYD and fluoropyrimidines is still in development, the authors have concluded, based on current evidence, that c.1129-5923C>G, the minor allele at rs75017182 and causal allele associated with the “HapB3” haplotype, will be assigned an allele value of 0.75. For a heterozygous carrier, this corresponds to an activity score of 1.75. For these patients, the recommendation is to initiate treatment at 75% of the intended dose in cycle 1. The intended dose refer

Severe fluoropyrimidine-related toxicity · Pharmacol Res 2026

Bonne nouvelle pour la sécurité des patients : l’INCa et l’ANSM fixent enfin des règles claires pour adapter les doses de 5-FU en cas de déficit partiel en DPD. Décryptage de ce qui change dès aujourd’hui. Les fluoropyrimidines, dont le 5-fluorouracile administré par voie intraveineuse et la capécit

Chimiothérapie par 5-FU : des recommandations pour l'adaptation des dosesL'Institut National du Cancer (INCa) a récemment publié un avis d'experts visant à encadrer l'adaptation des doses de chimiothérapie à base de fluoropyrimidines, notamment le 5-FU et la Capécitabine, pour les patients présentan

This secondary analysis of a randomized clinical trial examines the use of pharmacogenetic-informed prescribing of fluoropyrimidines and/or irinotecan in patients with gastrointestinal cancer.

The protozoan pathogen Toxoplasma gondii is responsible for toxoplasmosis, a disease that can be deadly in immunocompromised patients and the developing fetus during pregnancy. Current treatments are widely considered to be suboptimal. We have recently reported that 5-fluoropyrimidines have highly promising anti-toxoplasmosis effects and are internalized by the parasite by a high-affinity uracil/uridine transporter, TgUUT1. Here, we attempt to identify the gene encoding this transport protein. The only nucleoside or nucleobase family identified in the T. gondii genome was the Equilibrative Nucleoside Transporter (ENT) family, with four members. Of these, TgAT1 is known to be purine-specific, and deletion of the TgENT2 and TgENT3 genes, either separately or jointly, did not affect uridine transport or sensitivity to 5-fluoropyrimidines. In contrast, depletion of TgENT1, an essential gene, resulted in a significant reduction in the uptake of both uracil and uridine but not of the amino acid tryptophan. Moreover, expression of TgENT1 in a Leishmania mexicana cell line with low endogenous uracil uptake rates significantly increased uracil uptake for these cells. We conclude that it is highly probable that TgENT1 encodes the T. gondii uracil/uridine transporter. On the basis of our previous results, we infer that TgENT1 likely also mediates the uptake of 5-fluoropyrimidines.

The protozoan pathogen Toxoplasma gondii is responsible for toxoplasmosis, a disease that can be deadly in immunocompromised patients and the developing fetus during pregnancy. Current treatments are widely considered to be suboptimal. We have recently reported that 5-fluoropyrimidines have highly promising anti-toxoplasmosis effects and are internalized by the parasite by a high-affinity uracil/uridine transporter, TgUUT1. Here, we attempt to identify the gene encoding this transport protein. The only nucleoside or nucleobase family identified in the T. gondii genome was the Equilibrative Nucleoside Transporter (ENT) family, with four members. Of these, TgAT1 is known to be purine-specific, and deletion of the TgENT2 and TgENT3 genes, either separately or jointly, did not affect uridine transport or sensitivity to 5-fluoropyrimidines. In contrast, depletion of TgENT1, an essential gene, resulted in a significant reduction in the uptake of both uracil and uridine but not of the amino acid tryptophan. Moreover, expression of TgENT1 in a Leishmania mexicana cell line with low endogenous uracil uptake rates significantly increased uracil uptake for these cells. We conclude that it is highly probable that TgENT1 encodes the T. gondii uracil/uridine transporter. On the basis of our previous results, we infer that TgENT1 likely also mediates the uptake of 5-fluoropyrimidines.

Clinically significant cardiotoxicity was found to be low among patients with CRC receiving trifluridine/tipiracil, but occurred even in those without traditional risk factors.

À la suite d’un cas de toxicité évitable enregistré en 2024 chez un patient traité par capécitabine (Xeloda) pour un cancer du rectum, l’ANSM rappelle les conditions de prescription et de délivrance des fluoropyrimidines. Depuis 2019, le...

Bacterial evolutionary adaptation to two chemotherapy dru...

This secondary analysis of a randomized clinical trial examines the use of pharmacogenetic-informed prescribing of fluoropyrimidines and/or irinotecan in patients with gastrointestinal cancer.

This secondary analysis of a randomized clinical trial examines the use of pharmacogenetic-informed prescribing of fluoropyrimidines and/or irinotecan in patients with gastrointestinal cancer.

Medicinski Glasnik

The 5-substituted 2-fluoropyrimidines was prepared by reaction of the corresponding chloropyrimidines with CsF in methylpyrrolidone or dimethylformamide. The 5-nitro-2fluoropyrimidine was synthesized more effective by using KF in the presen...