Toxicity/Benefit Ratio Optimization of Chemotherapy in Colorectal Cancer (CRC) Patients by Determination of Individual Genotypic Determinants

This study intends to optimize a fluorouracil/irinotecan chemotherapy regimen by the identification of individual thymidylate synthase (TS) and UDP-glucuronosyltransferase 1 (UGT1A1) polymorphisms before the first administration.

The results of this identification determine the chemotherapy type: high-dose irinotecan or not.

• Drug: irinotecan
  180 mg/m² or 260 mg/m² in 90 minutes every 15 days
• Drug: 5 fluorouracil
  400 mg/m² in bolus in day 1 and 2400 mg/m² in 46 hours perfusion

Inclusion Criteria:

• Has provided written informed consent prior to study-specific screening procedures, with the understanding that the patient has the right to withdraw from the study at any time without prejudice
• Ages between 18 and 85 years
• Histologically confirmed colorectal cancer
• No treatment for metastatic disease
• No irinotecan previously administered
• World Health Organization (WHO) performance status < 3

• Laboratory values :

  • neutrophils > 1.5 x 10^9/L;
  • platelet count > 100 x 10^9/L;
  • serum creatinine < 130µmol/L;
  • serum bilirubin < 2 x upper limit of normal (ULN);
  • ASAT and ALAT < 2.5 x ULN;
  • alkaline phosphatase < 5 x ULN.
• At least one measurable lesion by Response Evaluation Criteria in Solid Tumors (RECIST) criteria

Exclusion Criteria:

• History of another malignancy except cured basal cell carcinoma of the skin or carcinoma in situ of the uterine cervix, breast or bladder.
• Other concomitant anticancer therapy.
• Pregnant or lactating women.
• Women of childbearing potential unless using a reliable and appropriate contraceptive method.
• Symptomatic cerebral or leptospiral metastasis.
• Intestinal obstruction.
• Uncontrolled seizures (diabetes, severe infection).
• Clinically significant cardiac disease.
• Central nervous system disorders or severe psychiatric disability.
• Participation in any investigational study within 4 weeks.