Trial Information

Tailored Treatment of Metastatic Colorectal Cancer Based on Genetic Markers

The TS and MTHFR polymorphism has been investigated in a new study based on analysis of
normal tissue. The results indicated that protein with a 3/3 TS polymorphism or a MTHFR T
polymorphism had a significantly higher response rate and a longer time to progression than
the other groups when treated with bolus 5-FU.

Capecitabine is metabolised to 5-FU through a number of enzymatic steps. It is the first
rationally designed drug that is based upon the high concentration of thymidine
phosphorylase (TP) in many human tumors compared to normal tissue. TP is the last step in
the conversion of capecitabine to 5-FU and seems to be the limiting factor for the
activation. Capecitabine may to some extent mimic continues 5-FU infusion as opposed to
bolus 5-FU. A number of small investigations have indicated that patients with 2R/2R TS
polymorphism have a higher response rate than heterozygous patients.

The TS and MTHFR polymorphism analysis can easily be performed on sputum, which means an
easy collection and sending of the samples.

At present single agent chemotherapy is based on three drugs (5-FU, capecitabine, and
Irinotecan) with almost the same overall activity. It seems rational to investigate if
improvement can be obtained by tailoring the treatment according to gene polymorphism.