Pharmacogenomic and Pharmacokinetic Safety and Cost-saving Analysis in Patients Treated With Fluoropyrimidines

Study Overview
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Brief Summary
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The primary purpose of this study is to prospectively determine whether capecitabine and 5-FU-induced toxicity is preventable by dose reduction prior to start of the first administration in patients heterozygous or homozygous mutant for DPYD*2A, and to determine whether this strategy is cost-effective. Secondly, an individualized treatment algorithm for capecitabine and 5-FU therapy in DPYD*2A mutant patients will be developed and the pharmacokinetic profile of capecitabine and 5-FU will be assessed.

Detailed Description
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Patients exhibiting a genetically determined disorder (DPYD*2A) in the metabolic degradation of the frequently used anticancer agents capecitabine and 5-FU (fluoropyrimidines) are at high risk of development of severe and life-threatening toxicity during standard treatment with these compounds. Treatment and recovery of this fluoropyrimidine-induced severe toxicity often requires prolonged periods of hospitalization. Screening for DPYD*2A in patients to treat with fluoropyrimidine drugs with subsequent dose adjustments in mutant individuals prior to start of therapy will possibly reduce the number of severe toxicity events. Furthermore, by reducing the frequency and/or duration of hospitalization, substantial medical costs can be saved, making this a cost-effective strategy.

Official Title
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Pharmacogenomic and Pharmacokinetic Safety and Cost-saving Analysis in Patients Treated With Fluoropyrimidines

Conditions
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Neoplasms

Intervention / Treatment
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* Drug: Capecitabine, 5-fluorouracil


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histological proof of cancer patient is considered for treatment with capecitabine or 5-FU hetero- or homozygous mutant for DPYD*2A able and willing to give written informed consent able and willing to undergo blood sampling for pharmacokinetic analysis life expectancy 3 months or longer acceptable safety laboratory values (ANC, platelet count, ASAT, ALAT, creatinine, WHO performance status 0-2 no radio- or chemotherapy within the last 3 weeks prior to study entry Exclusion Criteria: patients with known alcoholism, drug addiction and/or psychotic disorders that are not suitable for adequate follow-up women who are pregnant or breast-feeding

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: DPYD*2A<br>Patients are screened for a DPD-deficiency. Patients with a DPYD*2A mutation are eligible for intervention with capecitabine/5-FU . | Drug: Capecitabine, 5-fluorouracil<br>* Patients to treat with capecitabine/5-FU will be screened prior to start of therapy for DPYD*2A. Patients heterozygous or homozygous mutant for DPYD*2A receive dose reductions of capecitabine/5-FU of at least 50% in the first two courses. In case this dose is tolerated well, doses will be increased. In addition, the pharmacokinetics of capecitabine/5-FU and their metabolites will be assessed in these patients.<br>* Other names: 5-FU;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| safety |  | during fluoropyrimidine treatment of the patient | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| cost-effectiveness |  | during fluoropyrimidine treatment of the patient | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pharmacogenetics, cost-benefit analysis, toxicity, antineoplastic drugs, Dihydropyrimidine Dehydrogenase