Fluoropyrimidine Tailored-dose Based on Uracil Concentration in Patients Treated for Digestive Carcinomas: Evaluation of Clinical Practice
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 334
- 试验地点
- 3
- 主要终点
- Overall survival according to plasma uracil concentration
研究概览
简要总结
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.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Retrospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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]).
排除标准
- •Age limit less than 18 years
- •Not treated with fluoropyrimidine based chemotherapy
- •Missing data for uracil concentration or chemotherapy dosage
研究组 & 干预措施
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].
干预措施: Fluoropyrimidine treatment (5-FU or capecitabine) and dosage (Drug)
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].
干预措施: Uracil dosage (Other)
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].
干预措施: Overall survival (Behavioral)
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].
干预措施: Fluoropyrimidine treatment (5-FU or capecitabine) and dosage (Drug)
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].
干预措施: Uracil dosage (Other)
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].
干预措施: Overall survival (Behavioral)
结局指标
主要结局
Overall survival according to plasma uracil concentration
时间窗: Last completion date March 30th 2021
次要结局
未报告次要终点