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

Completed

• Conditions: Digestive Carcinoma
• Interventions: Drug: Fluoropyrimidine treatment (5-FU or capecitabine) and dosage; Other: Uracil dosage; Behavioral: Overall survival

• Registration Number: NCT04918264
• Lead Sponsor: Hospices Civils de Lyon

Brief 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.

Detailed Description

Not available

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study Start: 2020-11-02
• Primary Completion: 2021-02-10
• Study Completion: 2021-04-15
• Status Verified: 2021-05
• Study First Submitted: 2021-06-02
• Study First Submitted QC: 2021-06-02
• Last Update Submitted: 2021-06-02
• Study First Posted: 2021-06-08
• Last Update Posted: 2021-06-08

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 334

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]).

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Exclusion Criteria

• Age limit less than 18 years
• Not treated with fluoropyrimidine based chemotherapy
• Missing data for uracil concentration or chemotherapy dosage

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Uracil concentration <16 ng/mL	Uracil dosage	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 \[Lyon\].
Uracil concentration ≥16 ng/mL	Overall survival	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 \[Lyon\].
Uracil concentration <16 ng/mL	Fluoropyrimidine treatment (5-FU or capecitabine) and dosage	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 \[Lyon\].
Uracil concentration <16 ng/mL	Overall survival	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 \[Lyon\].
Uracil concentration ≥16 ng/mL	Fluoropyrimidine treatment (5-FU or capecitabine) and dosage	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 \[Lyon\].
Uracil concentration ≥16 ng/mL	Uracil dosage	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 \[Lyon\].

Primary Outcome Measures

Name	Time	Method
Overall survival according to plasma uracil concentration	Last completion date March 30th 2021

Trial Locations

Locations (3)

Centre Hospitalier de Lyon Sud; 🇫🇷 Pierre-Bénite, France

Hopital Edouard Heriot, Centre Hospitalier de Lyon Sud [Lyon], Hopital de la Croix Rousse [Lyon]; 🇫🇷 Lyon, France

Hopital de la Croix Rousse; 🇫🇷 Lyon, France