Pharmacogenomic and Pharmacokinetic Safety and Cost-saving Analysis in Patients Treated With Fluoropyrimidines
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.
|Study Design:||Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Prevention
|Official Title:||Pharmacogenomic and Pharmacokinetic Safety and Cost-saving Analysis in Patients Treated With Fluoropyrimidines|
- safety [ Time Frame: during fluoropyrimidine treatment of the patient ] [ Designated as safety issue: Yes ]
- cost-effectiveness [ Time Frame: during fluoropyrimidine treatment of the patient ] [ Designated as safety issue: No ]
|Study Start Date:||May 2007|
|Study Completion Date:||October 2011|
|Primary Completion Date:||October 2011 (Final data collection date for primary outcome measure)|
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
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.
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00838370
|Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital|
|Amsterdam, Netherlands, 1066CX|
|Amsterdam, Netherlands, 1066|
|Canisius Wilhelmina Hospital|
|Nijmegen, Netherlands, 6532SZ|
|Principal Investigator:||Jan HM Schellens, MD, PhD||Netherlands Cancer Institute, Amsterdam, the Netherlands|