Pharmacogenomic and Pharmacokinetic Safety and Cost-saving Analysis in Patients Treated With Fluoropyrimidines
- Registration Number
- NCT00838370
- Lead Sponsor
- The Netherlands Cancer Institute
- Brief Summary
The primary purpose of this study is to prospectively determine whether capecitabine and 5-FU-induced toxicity is preventable by dose reduction prior to start of the first administration in patients heterozygous or homozygous mutant for DPYD\*2A, and to determine whether this strategy is cost-effective. Secondly, an individualized treatment algorithm for capecitabine and 5-FU therapy in DPYD\*2A mutant patients will be developed and the pharmacokinetic profile of capecitabine and 5-FU will be assessed.
- Detailed Description
Patients exhibiting a genetically determined disorder (DPYD\*2A) in the metabolic degradation of the frequently used anticancer agents capecitabine and 5-FU (fluoropyrimidines) are at high risk of development of severe and life-threatening toxicity during standard treatment with these compounds. Treatment and recovery of this fluoropyrimidine-induced severe toxicity often requires prolonged periods of hospitalization.
Screening for DPYD\*2A in patients to treat with fluoropyrimidine drugs with subsequent dose adjustments in mutant individuals prior to start of therapy will possibly reduce the number of severe toxicity events. Furthermore, by reducing the frequency and/or duration of hospitalization, substantial medical costs can be saved, making this a cost-effective strategy.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 22
- Histological proof of cancer
- patient is considered for treatment with capecitabine or 5-FU
- hetero- or homozygous mutant for DPYD*2A
- able and willing to give written informed consent
- able and willing to undergo blood sampling for pharmacokinetic analysis
- life expectancy 3 months or longer
- acceptable safety laboratory values (ANC, platelet count, ASAT, ALAT, creatinine,
- WHO performance status 0-2
- no radio- or chemotherapy within the last 3 weeks prior to study entry
- patients with known alcoholism, drug addiction and/or psychotic disorders that are not suitable for adequate follow-up
- women who are pregnant or breast-feeding
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description DPYD*2A Capecitabine, 5-fluorouracil Patients are screened for a DPD-deficiency. Patients with a DPYD\*2A mutation are eligible for intervention with capecitabine/5-FU .
- Primary Outcome Measures
Name Time Method safety during fluoropyrimidine treatment of the patient
- Secondary Outcome Measures
Name Time Method cost-effectiveness during fluoropyrimidine treatment of the patient
Trial Locations
- Locations (3)
Slotervaart Hospital
🇳🇱Amsterdam, Netherlands
Canisius Wilhelmina Hospital
🇳🇱Nijmegen, Netherlands
Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital
🇳🇱Amsterdam, Netherlands