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

Conditions: Colorectal or pancreas cancer

Registration Number: NL-OMON21471

Lead Sponsor: Catharina Hospital Eindhoven

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Pending

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. Age = 18 years
3. Able and willing to give written informed consent
4. WHO performance status 0-2
5. 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 non invasive

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
To determine the correlation between the baseline endogenous DPD substrate plasma ratios of DHU/U and DHT/T with the pharmacokinetics of 5-FU in patients with pancreas or colorectal cancer treated with intravenous 5-FU-based chemotherapy.

Secondary Outcome Measures

Name	Time	Method
-To determine the potential changes in U, DHU, T and DHT concentrations over time during the prolonged 5-FU infusion<br>-To determine the DHU/U, DHT/T and DHFU/FU ratios over time during 5-FU prolonged infusion <br>-To establish a cut-off concentration in a daily Dutch patient population for all measured analytes, their metabolites and ratios, including 5-FU, DHFU, U, DHU, T and DHT<br>-To determine the effect of DPYD genotype on the U, DHU, T and DHT concentrations and on the pharmacokinetics of 5-FU<br>-To determine the correlation between serious adverse events or 5-FU toxicity to AUC of 5-FU, DHU/U or DHT/T ratio<br>-To determine the effect of other genetic polymorphisms on the pharmacokinetics of 5-FU (if applicable)<br>