Clinical Research Papers:
Determining the optimal 5-FU therapeutic dosage in the treatment of colorectal cancer patients
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Ling Fang1,*, Yi Jiang2,*, Yuxian Yang2,*, Yuqiong Zheng3,*, Jin Zheng2,*, Hong Jiang4,*, Shengqi Zhang2, Lifang Lin1, Jieting Zheng1, Shuyao Zhang1 and Xiaowen Zhuang2
1 Pharmacy Intravenous Admixture Service, Cancer Hospital of Shantou University Medical College, Shantou, Guangdong, China
2 Digestive Medical Oncology, Cancer Hospital of Shantou University Medical College, Shantou, Guangdong, China
3 Clinical Laboratory, The First Afﬁliated Hospital of Shantou University Medical College, Shantou, Guangdong, China
4 Radiology department, Cancer Hospital of Shantou University Medical College, Shantou, Guangdong, China
* These authors have contributed equally to this work
Shuyao Zhang, email:
Xiaowen Zhuang, email:
Keywords: area under the plasma concentration-time curve, fluorouracil, dihydropyrimidine dehydrogenase, thymidylate synthetase
Received: April 19, 2016 Accepted: September 02, 2016 Published: September 12, 2016
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.
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