Evaluation of the oral uracil loading test as a sensitive, simple and cheap method to detect DPD deficiency.

Phase 2

Recruiting

Conditions: DPD deficiency
10027664
10027655

Registration Number: NL-OMON34231

Lead Sponsor: Diaconessenhuis Meppel / dr. J.G. Maring

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Recruiting

Sex: Not specified

Target Recruitment: 100

Inclusion Criteria

Case group
•Age > 18 years
•More than expected toxicity (grade 3-4, see table 2) after treatment with a 5-FU or capecitabine containing regimen, with clinical suspicions for DPD deficiency. All 5-FU or capecitabine containing chemotherapy schedules are allowed.
•Reduced DPD activity, i.e. < 5 nmol/mg/hour
•Signed informed consent;Control group
•Age > 18 years
•More than expected toxicity (grade 3-4, see table 2) after treatment with a 5-FU or capecitabine containing regimen, with clinical suspicions for DPD deficiency. All 5-FU or capecitabine containing chemotherapy schedules are allowed.
•Normal DPD activity i.e. > 5 nmol/mg/hour
•Signed informed consent

Exclusion Criteria

•Pregnancy
•Breast feeding
•Cimetidine use (due to drug-drug interactions with 5-fluorouracil and capecitabine)
•Renal failure (creatinine clearance less than 20 ml/min, calculated with Cockroft&Gault formula).

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>The main study parameters are the differences in uracil plasma levels and<br /><br>calculated uracil clearance between cases and controls. Based on these<br /><br>parameters, the sensitivity and specificity of the oral uracil loading test<br /><br>will be determined.</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>The secondary objectives of this study are:<br /><br>• to assess the sensitivity and specificity of the fasting endogenous<br /><br>uracil/dihydrouracil ratio in blood plasma as a potential screening tool for<br /><br>DPD deficiency<br /><br>• to investigate the causes of DPD deficiency and fluoropyrimidine toxicity on<br /><br>the molecular (genetic) level</p><br>