cancer, treated with capecitabine or 5-FU in DPD-deficient individuals
Conditions
Interventions
Trade Name: Xeloda
Pharmaceutical Form: Tablet
Other descriptive name: CAPECITABINE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 500-
Trade Name: Xeloda
Pharmac
Sponsors
NKI-AVL
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Histological or cytological proof of cancer 2. Patient is considered for treatment with capecitabine or 5-FU 3. Age 18 years 4. Able and willing to give written informed consent 5. Able and willing to undergo blood sampling for pharmacogenetic and pharmacokinetic analysis 6. Life expectancy ? 3 months allowing adequate follow up of toxicity evalution and antitumor activity 7. Minimal acceptable safety laboratory values a. ANC of 1.5 x 109 /L b. Platelet count of ? 100 x 109 /L c. Hepatic function as defined by serum bilirubin ? 1.5 x ULN, ALT and AST ? 2.5 x ULN; in case of liver metastases ALT and AST = 5 ULN d. Renal function as defined by serum creatinine ? 1.5 x ULN or creatinine clearance ? 50 ml/min (by Cockcroft-Gault formula). 8. WHO performance status of ? 2 9. No radio- or chemotherapy within the last 3 weeks prior to study entry Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Patients with known alcoholism, drug addiction and/or psychotic disorders in the history that are not suitable for adequate follow up 2. Women who are pregnant or breast feeding 3. Women of childbearing potential who refuse to use a reliable contraceptive method throughout the study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To prospectively determine whether fluoropyrimidine-induced toxicity is preventable by dose adjustment prior to start of the first administration based on the polymorphic status of the DPYD*2A polymorphism in DPYD, in comparison with retrospectively determined full-dose treated heterozygous patients.;Secondary Objective: • To determine whether adaptive dosing based on polymorphic status of DPYD*2A is cost-saving. • To validate an individualized treatment algorithm for 5-FU and capecitabine therapy based on the polymorphic status of DPYD*2A. • To assess the pharmacokinetic profile of capecitabine and 5-FU in DPYD*2A mutant patients given reduced dosages of the respective drugs. • To estimate the frequency of the DPYD*2A polymorphism in a Dutch cancer population. ;Primary end point(s): To prospectively determine whether fluoropyrimidine-induced toxicity is preventable by dose adjustment prior to start of the first administration based on the polymorphic status of the DPYD*2A polymorphism in DPYD, in comparison with retrospectively determined full-dose treated heterozygous patients. | — |
Countries
Netherlands
Outcome results
None listed