Correlation between endogenous DPD substrate concentrations and the pharmacokinetics and toxicity of 5-fluorouracil in patients with colorectal or pancreas cancer

Completed

Conditions: Colon cancer
colorectalcarcinoma
pancreas cancer
pancreascarcinoma
10017991

Registration Number: NL-OMON48600

Lead Sponsor: Catharina-ziekenhuis

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 50

Inclusion Criteria

1) Pathologically confirmed malignancy for which treatment with 5-FU is
indicated in the FOLFOX, FOLFIRI or FOLFIRINOX regimen.
2) Minimal acceptable safety laboratory values defined as
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, ALAT and ASAT *
2.5 x ULN; in case of liver metastases ALAT and ASAT * 5 x ULN.
d. renal function as defined by MDRD >30 ml/min

Exclusion Criteria

1. Patients with known substance abuse, psychotic disorders, and/or other
diseases expected to interfere with study or the patient*s safety
2. Women who are pregnant or breast feeding
3. Patients in whom the bolus injection will be skipped due to e.g. toxicity of
previous chemo therapy regimen.

Study & Design

Study Type: Observational invasive

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>The primary endpoint of the study are the plasma concentrations of 5-FU, DHFU<br /><br>and endogenous biomarkers U, DHU, T and DHT at all time points by using<br /><br>LC-MS/MS.</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>- Ratios of DHU/U, DHT/T and DHFU/FU will be calculated by using the plasma<br /><br>concentration<br /><br>- Determine DPYD genotype for each patient. If applicable, additional SNP<br /><br>analysis within the DPYD gene will be conducted at study end<br /><br>- DPD enzym activity<br /><br>- Severe adverse events following 5-FU infusion, including:<br /><br>* Toxicity-related hospitalization<br /><br>* Change in dose intensity: prolonged interval or dose reduction<br /><br>* Myelosuppression (leukocytes, neutrophils and thrombocytes) grade 3<br /><br>according to CTC-AE criteria<br /><br> Other toxicities including grade *3 mucositis and diarrhoea according to the<br /><br>CTC-AE criteria</p><br>