A combination of pre-screening for DPD deficiency by genotyping/phenotyping methods and pharmacokinetics-guided dosing of 5-FU for precision treatment to prevent severe toxicity in gastrointestinal cancer patients

Recruiting

Conditions: Gastrointestinal cancer

Registration Number: NL-OMON29105

Lead Sponsor: Isala

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Recruiting

Sex: Not specified

Target Recruitment: 65

Inclusion Criteria

•age 18 years and older
•histological proof of gastro-intestinal cancer
•patient is considered for treatment with capecitabine or 5-FU
•acceptable safety laboratory values
•ECOG performance status 0-2
•able and willing to give written informed consent
•able and willing to undergo blood sampling for DPYD genotyping, DPD phenotyping and pharmacokinetic analysis

Exclusion Criteria

•prior chemotherapy with fluoropyrimidines
•symptomatic or uncontrolled central nervous system metastases
•patient who cannot submit itself to the formal follow-up for psychological, social, family or geographical reasons
•women who are pregnant or breast-feeding
•women not consenting to use adequate contraceptive precautions during the study
•significant serious pathology or any instable medical condition (cardiac pathology uncontrolled, myocardial infarction within 6 months before enrolment, systemic active uncontrolled infection, cirrhosis (Child-Pugh score C), renal failure (GFR < 20 ml/min))
•any investigational agent within 4 weeks before enrolment
•cimetidine or sorivudine use (due to drug-drug interactions with 5-fluorouracil and capecitabine)

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
•DPYD genotyping on 4 common mutations: (E412E (c.1236G>A; rs56038477), IVS14 ds+1G>A (2A; c.1905+1G>A; rs3918290)), D949V (c.2846A>T; rs67376798), I560S (13; c.1679T>G; rs55886062))<br>•5-FU clearance (Cl) at steady state <br>•Final TDM adapted 5-FU dose

Secondary Outcome Measures

Name	Time	Method
•The incidence of 5-FU related toxicities<br>•U/DHU ratio<br>•DPD phenotype (EM, IM, and PM)<br>•5-FU doses<br>•Dosage adjustment <br>•Time to reach target AUC (cycle number)