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

NCT04918264 | Completed

• 1 other identifier: 69HCL21_0489
• Study Type: observational
• Target: 334
• Locations: 1 country
• Sites: 3

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.

Conditions

Digestive Carcinoma

Keywords

Uracil; DPYD; Toxicity; Clinical practice; Overall survival

Outcome Measures

Primary Outcomes (1)

• Overall survival according to plasma uracil concentration

  Last completion date March 30th 2021

Study Arms (2)

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 \[Lyon\].

Drug: Fluoropyrimidine treatment (5-FU or capecitabine) and dosage; Other: Uracil dosage; Behavioral: Overall survival

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 \[Lyon\].

Drug: Fluoropyrimidine treatment (5-FU or capecitabine) and dosage; Other: Uracil dosage; Behavioral: Overall survival

Interventions

Fluoropyrimidine treatment (5-FU or capecitabine) and dosage 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 concentration <16 ng/mL; Uracil concentration ≥16 ng/mL

Uracil dosage OTHER

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

Uracil concentration <16 ng/mL; Uracil concentration ≥16 ng/mL

Overall survival 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; Uracil concentration ≥16 ng/mL

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients will be included in this retrospective study if they have digestive cancer and an uracil dosage performed between February 2018 to January 2020, and if they 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 \[Lyon\]. The following characteristics will be review: histology, stage (localized vs metastatic disease), chemotherapy regimen, dose percentage of fluoropyrimidine, fluoropyrimidine induced-toxicity, time to failure and overall survival.

You may qualify if:

• 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 \[Lyon\]).

You may not qualify if:

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

Sponsors & Collaborators

• Hospices Civils de Lyon: lead

Study Sites (3)

Hopital Edouard Heriot, Centre Hospitalier de Lyon Sud [Lyon], Hopital de la Croix Rousse [Lyon]

Lyon, 69003, France

Location

Hopital de la Croix Rousse

Lyon, 69004, France

Location

Centre Hospitalier de Lyon Sud

Pierre-Bénite, 69495, France

Location

MeSH Terms

Interventions

Fluorouracil; Capecitabine

Intervention Hierarchy (Ancestors)

Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 2, 2021
• First Posted: June 8, 2021
• Study Start: November 2, 2020
• Primary Completion: February 10, 2021
• Study Completion: April 15, 2021
• Last Updated: June 8, 2021

Record last verified: 2021-05

Locations

FR (3)