Determining the optimal 5-FU therapeutic dosage in the treatment of colorectal cancer patients

Abstract

Fluorouracil (5-FU) has been wildly used as a primary medication in the treatment of solid tumors including colorectal cancer. The treatment efficacy and toxicity of 5-FU varies greatly among individuals, suggesting a need for individualized regimen for cancer patients. The present study analyzed the blood concentration of 5-FU and its therapeutic efficacy and toxicity, evaluated the relationship of AUC (area under the plasma concentration-time curve), and the protein expression of DPD (dihydropyrimidine dehydrogenase) and TS (thymidylate synthetase), and therapeutic efficacy and toxicity. It was found that the AUC of 5-FU was 34.16±14.83mg·h/L in this cohort of study. The immunohistochemical analysis revealed 38.96% and 81.82% positive staining for DPD and TS in colorectal cancer tissues, respectively. We demonstrated that the expression of TS is positively correlated with the expression of DPD. There was a positive correlation between AUC and therapeutic efficacy, and gastrointestinal tract and neural toxicity. The expression of neither DPD nor TS had significant correlations with therapeutic efficacy and toxicity. Based on the blood 5-FU concentration and its relationship with treatment efficacy and toxicity, we determined an optimal therapeutic dosage of 5-FU to be equivalent to an AUC=28.03-38.94mg·h/L. Our study will be helpful in providing an individualized medical regimen for the treatment of colorectal cancer patients.