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Fluoropyrimidine Tailored-dose Based on Uracil Concentration in Patients Treated for Digestive Carcinomas: Evaluation of Clinical Practice

NCT04918264 · Status: COMPLETED · Type: OBSERVATIONAL · Enrollment: 334

Last updated 2021-06-08

No results posted yet for this study

Summary

Digestive carcinomas chemotherapies regimen are mostly based on fluoropyrimidine drugs (5-Fluorouracil (5-FU) or capecitabine). 5-FU is mainly catabolised by dihydropyrimidine dehydrogenase (DPD) and partial or complete DPD deficiency can cause severe adverse reactions. Different strategies have been proposed to predict DPD deficiency; the two main approaches are phenotyping the enzyme activity (directly or indirectly), or genotyping the four main polymorphisms associated with 5-FU-toxicity. In February 2018, the French medicines agency (Agence nationale de sécurité du médicament et des produits de santé, ANSM) recommended DPD genotyping for all patients receiving fluoropyrimidine-based treatment to improve its safety as compared to the European Medicines Agency (EMA)13 and others pharmacogenetics working group.

In December 2018, a new guideline from the French cancer institute (Institut National Du Cancer, INCa) and the French health authority (Haute Autorité de Santé, HAS) recommended the measurement of the uracil blood level before genotyping DPD and dose adaptation if this level is greater than 16 ng/mL. The aim herein is to assess how this recommendation has been implemented in clinical routine. 5-FU displays a dose-response relationship regarding both its efficacy and its toxicity, did tailored-dose impair the treatment efficacy as it decreased the risk of toxicity? To address that matter we conducted a retrospective study to evaluate how fluoropyrimidine dosage is adapted to uracil concentration with an emphasis on how patients outcome were affected. We compared time to failure and overall survival between patients with an uracil concentration \< 16 ng/mL and \> or = 16 ng/mL.

Conditions

  • Digestive Carcinoma

Interventions

DRUG

Fluoropyrimidine treatment (5-FU or capecitabine) and dosage

In each group with an uracil dosage; at cycle 1; capecitabine or continuous 5-FU dose percentage will be evaluate retrospectively in our database

OTHER

Uracil dosage

For each patient, uracil concentration will be evaluate and patients will be compared based on 16 ng/mL as threshold.

BEHAVIORAL

Overall survival

For each group of patient, on 16 ng/mL as threshold for uracil concentration, overall survival will be compared betwen the two groups of patients (Uracil \<16 vs Uracil ≥16).

Sponsors & Collaborators

  • Hospices Civils de Lyon

    lead OTHER

Eligibility

Min Age
18 Years
Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2020-11-02
Primary Completion
2021-02-10
Completion
2021-04-15

Countries

  • France

Study Locations

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Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT04918264 on ClinicalTrials.gov