Gastrointestinal cancer
Conditions
Interventions
5-FU dose adaptation according to IATDMCT guideline
Sponsors
Isala
Eligibility
Inclusion criteria
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
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)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| •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)) •5-FU clearance (Cl) at steady state •Final TDM adapted 5-FU dose | — |
Secondary
| Measure | Time frame |
|---|---|
| • The incidence of 5-FU related toxicities • U/DHU ratio • DPD phenotype (EM, IM, and PM) • 5-FU doses • Dosage adjustment • Time to reach target AUC (cycle number) | — |
Contacts
Public ContactPawida Veluwenkamp-Worawutputtapong
Isala klinieken
Outcome results
None listed