Clinical trial NCT04918264: Fluoropyrimidine Tailored-dose Based on Uracil Concentration in Patients Treated for Digestive Carcinomas: Evaluation of Clinical Practice
Official title: Fluoropyrimidine Tailored-dose Based on Uracil Concentration in Patients Treated for Digestive Carcinomas: Evaluation of Clinical Practice
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Digestive Carcinoma
Keywords: Uracil
DPYD
Toxicity
Clinical practice
Overall survival
Lead sponsor: Hospices Civils de Lyon
Sponsor class: OTHER
First posted: 2021-06-08
Enrollment: 334
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
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.

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.


Eligibility criteria: 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 \[Lyon\]).

Exclusion Criteria:

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

Primary outcomes:
measure: Overall survival according to plasma uracil concentration
timeFrame: Last completion date March 30th 2021
Secondary outcomes:
Other outcomes:
Locations:
city: Lyon
country: France
facility: Hopital Edouard Heriot, Centre Hospitalier de Lyon Sud [Lyon], Hopital de la Croix Rousse [Lyon]
city: Lyon
country: France
facility: Hopital de la Croix Rousse
city: Pierre-Bénite
country: France
facility: Centre Hospitalier de Lyon Sud
Study officials:
References: