Implementation and Quality Assurance of DPYD-genotyping in Patients Treated With Fluoropyrimidines
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 722
- 试验地点
- 1
- 主要终点
- Adverse events
研究概览
简要总结
The purpose of this study is to examine the benefits of a clinical implementation of a DPYD-genotype test to patients starting treatment with fluoropyrimidines (Fluorouracil (5-FU), capecitabine, tegafur).
详细描述
Patients with specific genetic mutations in the DPYD-gene have lower activity of the dihydropyrimidine dehydrogenase (DPD) enzyme, which is the rate-limiting enzyme in the metabolism of fluoropyrimidines. Fluoropyrimidines are commonly used as chemotherapeutic drugs and include 5-Fluorouracil, capecitabine, and tegafur. Patients with decreased DPD activity are at higher risk of serious adverse events when treated with standard doses of fluoropyrimidines
This study will examine the clinical implementation of the pre-emptive DPYD-genotype test. The test will analyze four of the most common genetic mutations(SNPs) in the DPYD-gene that leads to significant decreased DPD-activity
In patients with DPYD-variant mutations, the recommended starting dose is 50%. This dose reduction will possibly reduce the rate of serious adverse events. Patients who are homozygous or compound heterozygous for a DPYD-mutation will not be treated with fluoropyrimidines due to the high risk of fatal adverse effects.
Aim To reduce the overall incidence of severe adverse reactions(grade >= 3) to chemotherapy regimens containing 5-FU, capecitabine, or S1 in an unselected population of colorectal, non-colorectal GI cancer, or breast cancer patients through pre-emptive DPYD-genotyping.
Design The investigators will conduct an open clinical trial using historical controls. The investigators will implement pre-emptive genotype testing of about 1000 consecutive patients subject to 5-FU, capecitabine, or S1 treatment for colorectal, non-colorectal GI, or breast cancer. The investigators will use a historical control group of about 500 consecutive similar patients.
研究设计
- 研究类型
- Observational
- 观察模型
- Other
- 时间视角
- Cross Sectional
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
- •Patients with cancer that are eligible for systemic treatment with 5-FU, capecitabine, or tegafur.
排除标准
- •Patients that earlier have been treated with 5-FU, capecitabine, or tegafur
结局指标
主要结局
Adverse events
时间窗: Up to 6 months
Rate of grade 3-5 adverse events (CTCAE) Version 5.0
次要结局
- Length of hospital stay(Up to 6 months)
- 5-FU or capecitabine or S1-related mortality, all patients(Up to 6 months)
- Overall mortality, all patients(Up to 6 months)
- Overall mortality, DPYD variant carriers(Up to 6 months)
- Rate of discontinuation of fluoropyrimidines due to adverse events(Up to 6 months)
- 5-FU or capecitabine or S1-related mortality, DPYD variant carriers(Up to 6 months)
研究者
Per Damkier
MD, ph.d. Clinical Professor,
University of Southern Denmark