Determination of plasma uracil as a screening for dihydropyrimidine dehydrogenase deficiency: clinical application in oncological treatments.

Eduardo Tejedor-Tejada, Daniel Rubio Calvo, Antonio Garc��a Andreo
Author Information
  1. Eduardo Tejedor-Tejada: Pharmacy, Torrecardenas University Hospital, Almeria, Spain edutejedor91@gmail.com. ORCID
  2. Daniel Rubio Calvo: Pharmacy, Poniente Hospital, El Ejido, Spain.
  3. Antonio Garc��a Andreo: Laboratory, Torrecardenas University Hospital, Almeria, Spain.

Abstract

AIMS: Treatment with dihydropyrimidines poses a significant risk of serious adverse reactions for patients with dihydropyrimidine dehydrogenase (DPD) deficiency. This study seeks to analyse the correlation between DPD deficiency and plasmatic uracil values in patients who are candidates for a fluoropyrimidine scheme. It also studies the incidence of adverse events (AEs) in patients with DPD deficiency established with plasmatic uracil determination.
METHODS: This was a retrospective observational study conducted in a tertiary level establishment from September 2020 to April 2021. Patients included were diagnosed with gastrointestinal tumours, were of good status, and were initiated into a fluoropyrimidine-based regimen. The incidence and grade of AEs, according Common Terminology Criteria for Adverse Events (CTCAE), were collected and compared in patients with and without DPD deficiency.
RESULTS: 119 patients diagnosed with gastrointestinal cancer met the inclusion criteria. In 92 (77%) patients there was no DPD deficiency according to plasmatic uracil thresholds. In the group of patients without deficit, dose reductions oscillated between 10-25% (mean 17.4%). In the no DPD deficiency group, 43 (46%) patients experienced AEs. Patients who had a DPD deficiency according to plasmatic uracil measurements were started on a 5-fluorouracil (5-FU) regimen with a dose reduction of 15-50% (mean 35%). In this group, 12 patients (44%) experienced some AEs.
CONCLUSION: New research is needed to clarify the correlation between plasma uracil values and DPD deficiency to achieve an optimal balance between clinical benefit and toxicity.

Keywords

References

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MeSH Term

Humans
Dihydropyrimidine Dehydrogenase Deficiency
Uracil
Dihydrouracil Dehydrogenase (NADP)
Fluorouracil
Retrospective Studies

Chemicals

Uracil
Dihydrouracil Dehydrogenase (NADP)
Fluorouracil

Word Cloud

Created with Highcharts 10.0.0patientsDPDdeficiencyuracilplasmaticAEsaccordinggroupadversedihydropyrimidinedehydrogenasestudycorrelationvaluesincidencePatientsdiagnosedgastrointestinalregimenwithoutdosemeanexperiencedplasmaclinicaleducationpharmacyAIMS:TreatmentdihydropyrimidinesposessignificantriskseriousreactionsseeksanalysecandidatesfluoropyrimidineschemealsostudieseventsestablisheddeterminationMETHODS:retrospectiveobservationalconductedtertiarylevelestablishmentSeptember2020April2021includedtumoursgoodstatusinitiatedfluoropyrimidine-basedgradeCommonTerminologyCriteriaAdverseEventsCTCAEcollectedcomparedRESULTS:119cancermetinclusioncriteria9277%thresholdsdeficitreductionsoscillated10-25%174%4346%measurementsstarted5-fluorouracil5-FUreduction15-50%35%1244%CONCLUSION:NewresearchneededclarifyachieveoptimalbalancebenefittoxicityDeterminationscreeningdeficiency:applicationoncologicaltreatmentscontinuingequipmentdesigngenetictherapymedicaloncology

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