Cancer (breast cancer colorectal cancer gastric cancer)
Conditions
Interventions
Patients with a pretreatment serum uracil concentration above 16 ng/ml and
patients with c.1236G>A or c.2846A>T variant wil receive a 50% dose reduction.
Patients with a homozygous or compound heter
Sponsors
Antoni van Leeuwenhoek Ziekenhuis
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. Pathologically confirmed malignancy for which treatment with a fluoropyrimidine is considered to be in the patient*s best interest 2. Patient need to be of Western descent 3. Age >= 18 4. Able and willing to give written informed consent 5. WHO performance status of 0, 1 or 2 6. Able and willing to undergo extra blood sampling for study related analysis 7. Adequate baseline patient characteristics (complete blood count, hepatic function which involves serum bilirubin, AST, ALT, and renal function)
Exclusion criteria
Exclusion criteria: 1. Prior treatment with fluoropyrimidines 2. Patients with known substance abuse, psychotic disorders, and/or other diseases expected to interfere with study or the patient*s safety 3. Patients treated with the combination of a fluoropyrimidine and irinotecan
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary endpoint in this study is the incidence of severe treatment-related toxicity (NCI CTC-AE grade 3 to 5) in DPYD wildtype patients treated with a reduced dose based on DPD phenotype compared to DPYD wildtype patients treated with a full dose of fluoropyrimidines after 2 cycles, based on uracil concentration. | — |
Secondary
| Measure | Time frame |
|---|---|
| • Incidence of grade 3 - 5 toxicity in patients given a reduced starting dose of fluoropyrimidines • Incidence of toxicity-related hospital admissions • Assessment of pharmacokinetics in patients given a reduced starting dose of fluoropyrimidines • Incidence of treatment delay due to prospective combined DPYD genotyping and DPD phenotyping. • Costanalysis of combined upfront genotypic and phenotypic assessment of DPD deficiency • Association between time of administration capecitabine and grade 3 - 5 toxicity • Association between geriatric frailty parameters and grade 3-5 toxicity or early treatment discontinuation • Association between the duration between capecitabine administration and radiotherapy and grade 3 -5 toxicity • Association between circadian rhythm and concentration of the serum uracil • Similarity of patients with an uracil concentration above 16 ng/ml and patients who would have received a dose reduction if you looked at DHU/U- ratio retrospectively • Exploration and /or correlation between other genetic markers and capecitabine toxicity | — |
Countries
Netherlands
Outcome results
None listed