Evidence map›Paper›PMID 39702680›Full record

ArticleCancer chemotherapy and pharmacology2024

Plasma clearance of 5-fluorouracil is more influenced by variations in glomerular filtration rate than by uracil concentration.

Alice Matheux, Laurine Collas, Maelle Grisard, Léa Goulaieff, François Ghiringhelli, Leïla Bengrine-Lefevre, Julie Vincent, Francoise Goirand, Bernard Royer, Antonin Schmitt

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Article in Cancer chemotherapy and pharmacology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
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  4. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Alice MatheuxPharmacology and Toxicology Department, Pharmacology and Toxicology Laboratory, Dijon University Hospital, 2, Rue Angélique Ducoudray, 21000, Dijon, France. alice.matheux@chu-dijon.fr.ORCID 0000-0003-2572-4606
Laurine CollasPharmacy Department, Centre Georges-François Leclerc, Dijon, France.
Maelle GrisardPharmacology and Toxicology Department, Pharmacology and Toxicology Laboratory, Dijon University Hospital, 2, Rue Angélique Ducoudray, 21000, Dijon, France.
Léa GoulaieffPharmacology and Toxicology Department, Pharmacology and Toxicology Laboratory, Dijon University Hospital, 2, Rue Angélique Ducoudray, 21000, Dijon, France.
François GhiringhelliOncology Department, Centre Georges-François Leclerc, Dijon, France.
Leïla Bengrine-LefevreOncology Department, Centre Georges-François Leclerc, Dijon, France.
Julie VincentOncology Department, Centre Georges-François Leclerc, Dijon, France.
Francoise GoirandPharmacology and Toxicology Department, Pharmacology and Toxicology Laboratory, Dijon University Hospital, 2, Rue Angélique Ducoudray, 21000, Dijon, France.
Bernard RoyerLaboratoire de Pharmacologie Clinique et Toxicologie, CHU Besançon, Besançon, France.
Antonin SchmittPharmacy Department, Centre Georges-François Leclerc, Dijon, France.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectivesThe use of plasma uracil measurements to detect dihydropyrimidine dehydrogenase (DPD) deficiency is one of the methods for preventing toxicities associated with fluoropyrimidines, including 5-Fluorouracil (5-FU). Unfortunately, this measurement is subject to variations, that may lead to unnecessary dosage reductions and therefore to a reduced efficacy of treatment. Recently, new factors such as hepatic and renal impairment have been proposed as also influencing uracil concentration. The aim of our study was therefore to study the influence of renal or hepatic function on 5-FU clearance. PATIENTS AND

methodsThis was a retrospective study, using patients treated with 5-FU between September 1, 2018 to December 1, 2022 in a French Clinical Cancer Center. Patients were included after treatment with 5FU and therapeutic monitoring of 5FU concentrations after each course of chemotherapy. For each patient, DPD phenotyping by uracil concentration measurement was determined before the first course of 5FU. Blood samples were then taken the day after the start of the 5-FU infusion, between 8 and 10 am, for the first three cycles of 5-FU. With the exception of uracil concentration, which was determined only once, the various data were recorded for each course of 5FU chemotherapy performed. Patients with incomplete information (missing one of the above parameters) were excluded from the database.

resultsWe included 227 patients, corresponding to 227 uracil concentrations and 575 5-FU concentrations. In an original development, our results show for the first time that 5-FU clearance was proportionally correlated with eGFR (calculated according to CKD-EPI formula). Although we failed to demonstrate this hypothesis significantly, we observed that 5-FU clearance may be more dependent on eGFR than on uracil concentration for low uracil concentrations values.

conclusionOur study reinforces the still poorly accepted idea of the value of focusing on eGFR in 5-FU dose adjustment.

Indexed as

Antimetabolites, AntineoplasticFluorouracilGlomerular Filtration RateUracilAdultAgedAged, 80 and overDihydropyrimidine Dehydrogenase DeficiencyDihydrouracil Dehydrogenase (NADP)FemaleHumansMaleMetabolic Clearance RateMiddle AgedNeoplasmsRetrospective StudiesAntimetabolites, AntineoplasticDihydrouracil Dehydrogenase (NADP)FluorouracilUracil5-FU dose adjustmenteGFRKidney failureLiver function tests

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.