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

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

334 participants

Study Classification

OBSERVATIONAL

Study Start Date

2020-11-02

Study Completion Date

2021-04-15

Brief Summary

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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.

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Detailed Description

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Conditions

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Digestive Carcinoma

Study Design

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Observational Model Type

COHORT

Study Time Perspective

RETROSPECTIVE

Study Groups

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Uracil concentration <16 ng/mL

Patients were included in this arm if they have digestive cancer and an uracil dosage \<16 ng/mL performed between February 2018 to January 2020, and if they received at least one cycle of fluoropyrimidine-based chemotherapy in one of the four oncology departments (Hopital Edouard Heriot \[Lyon\], Centre Hospitalier de Lyon Sud \[Lyon\], Hopital de la Croix Rousse \[Lyon\].

Fluoropyrimidine treatment (5-FU or capecitabine) and dosage

Intervention Type DRUG

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

Uracil dosage

Intervention Type OTHER

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

Overall survival

Intervention Type BEHAVIORAL

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).

Uracil concentration ≥16 ng/mL

Patients were included in this arm if they have digestive cancer and an uracil dosage \<16 ng/mL performed between February 2018 to January 2020, and if they received at least one cycle of fluoropyrimidine-based chemotherapy in one of the four oncology departments (Hopital Edouard Heriot \[Lyon\], Centre Hospitalier de Lyon Sud \[Lyon\], Hopital de la Croix Rousse \[Lyon\].

Fluoropyrimidine treatment (5-FU or capecitabine) and dosage

Intervention Type DRUG

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

Uracil dosage

Intervention Type OTHER

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

Overall survival

Intervention Type BEHAVIORAL

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).

Interventions

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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

Intervention Type DRUG

Uracil dosage

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

Intervention Type OTHER

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).

Intervention Type BEHAVIORAL

Eligibility Criteria

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Inclusion Criteria

* Digestive cancer
* An uracil dosage performed between February 2018 to January 2020
* Received at least one cycle of fluoropyrimidine-based chemotherapy in one of the three oncology departments (Hopital Edouard Heriot \[Lyon\], Centre Hospitalier de Lyon Sud \[Lyon\], Hopital de la Croix Rousse \[Lyon\]).