Neoplasms
Conditions
Keywords
Fluoropyrimidines, DPYD, Genotyping, Capecitabine, 5-Fluorouracil, 5-FU, Non-Western
Brief summary
This is a observational, multicenter study to identify novel variants of the DPYD gene which are possible deleterious in patients of non-Western descent.
Detailed description
Research has shown that DPYD-guided dose-individualization based on 4 DPYD variants (DPYD\*2A, c.1236G\>A, c.2846A\>T and c.1679T\>G) can significantly reduce severe fluoropyrimidine-related toxicity. However, these 4 variants are most likely not predictive for toxicity in patients of non-Western descent. In this study the DPYD gene of patients of non-Western descent will be sequenced to identify novel variants that could be associated with a reduced DPD enzyme activity and an increased risk of developing severe fluoropyrimdine-related toxicity. Additionally, the ability to predict if a DPYD variant is possibly deleterious by a recombinant model systen (DPYD-varifier) will be studied.
Interventions
GENETICSequencing of DPYD gene
The DPYD gene of non-Western patients will be sequenced to identify DPYD variants that are possibly associated with an increased risk of developing severe fluoropyrimidine-related toxicity.
Sponsors
The Netherlands Cancer Institute
Erasmus Medical Center
Haga Hospital
Medical Center Haaglanden
Leiden University Medical Center
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Pathologically confirmed malignancy for which treatment with a fluoropyrimidine is considered to be in the patient's best interest * Patients need to be self-declared non-Western * Age 18 years and older * Able and willing to give written informed consent * WHO performance status of 0, 1 or 2 * Life expectancy of at least 12 weeks * Able and willing to undergo blood sampling for study related analysis * Adequate baseline patient characteristics (complete blood count, hepatic function which involves serum bilirubin, ASAT, ALAT, and renal function)
Exclusion criteria
* Prior treatment with fluoropyrimidines * Patients with known substance abuse, psychotic disorders, and/or other diseases expected to interfere with study or the patient's safety
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Presence of variants of the DPYD gene that are possibly associated with an increased risk of severe fluoropyrimidine-related toxicity in patients of non-Western descent | Patients will be followed for the first 2 cycles (each cycle is 28 days). |
Secondary
| Measure | Time frame |
|---|---|
| DPD enzyme activity of patients carrying a novel DPYD variant compared to wildtype patients measured in peripheral blood mononuclear cells (PBMCs) | Through study completion, an average of 2 years |
| Ability of the DPYD-varifier to predict if a novel DPYD variant is deleterious | Through study completion, an average of 2 years |
| Frequency of DPYD variants per ethnic origin | Through study completion, an average of 2 years |
| Correlation between genetic variants in genes other than DPYD and fluoropyrimidine-related toxicity | Through study completion, an average of 2 years |
Contacts
Primary ContactHans Gelderblom, Prof.
Backup ContactJesse Swen, PhD
Outcome results
None listed