Tailored Treatment in Metastatic Colorectal Cancer
To compare the response rate of single agent chemotherapy in advanced colorectal cancer given as standard treatment versus tailored treatment in a randomised phase III trial.
Metastatic Colorectal Cancer
Drug: Capecitabine, Irinotecan, 5-Fluorouracil+Calciumfolinat
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Tailored Treatment of Metastatic Colorectal Cancer Based on Genetic Markers|
- The primary end point is
- Response according to RECIST criteria.
- Secondary end points are
- Progression free survival
- Overall survival
|Study Start Date:||November 2006|
|Estimated Study Completion Date:||March 2009|
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.
|Aalborg, Denmark, 9100|
|Aarhus University Hospital|
|Aarhus, Denmark, 8000|
|Copenhagen, Denmark, 2100|
|Sydvestjysk Hospital Esbjerg|
|Esbjerg, Denmark, 6700|
|Herlev, Denmark, 2730|
|Herning Central Hospital|
|Herning, Denmark, 7400|
|Næstved, Denmark, 4700|
|Odense University Hospital|
|Odense, Denmark, 5000|
|Roskilde, Denmark, 4000|
|Viborg, Denmark, 8800|
|Principal Investigator:||Anders Jakobsen, Prof, MDSc||Department of Oncology, Vejle Hospital, 7100 Vejle, DK-Denmark|