title: 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±14.83mgmg·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=28.03-38.94mgmg·h/L. Our study will be helpful in providing an individualized medical regimen for the treatment of colorectal cancer patients.
authors.affiliation: Pharmacy Intravenous Admixture Service, Cancer Hospital of Shantou University Medical College, Shantou, Guangdong, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Fang
authors.affiliation: Digestive Medical Oncology, Cancer Hospital of Shantou University Medical College, Shantou, Guangdong, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Digestive Medical Oncology, Cancer Hospital of Shantou University Medical College, Shantou, Guangdong, China.
authors.forename: Yuxian
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Clinical Laboratory, The First Afﬁliated Hospital of Shantou University Medical College, Shantou, Guangdong, China.
authors.forename: Yuqiong
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Digestive Medical Oncology, Cancer Hospital of Shantou University Medical College, Shantou, Guangdong, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Zheng
authors.affiliation: Radiology department, Cancer Hospital of Shantou University Medical College, Shantou, Guangdong, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Jiang
authors.affiliation: Digestive Medical Oncology, Cancer Hospital of Shantou University Medical College, Shantou, Guangdong, China.
authors.forename: Shengqi
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Pharmacy Intravenous Admixture Service, Cancer Hospital of Shantou University Medical College, Shantou, Guangdong, China.
authors.forename: Lifang
authors.initials: L
authors.lastname: Lin
authors.affiliation: Pharmacy Intravenous Admixture Service, Cancer Hospital of Shantou University Medical College, Shantou, Guangdong, China.
authors.forename: Jieting
authors.initials: J
authors.lastname: Zheng
authors.affiliation: Pharmacy Intravenous Admixture Service, Cancer Hospital of Shantou University Medical College, Shantou, Guangdong, China.
authors.forename: Shuyao
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Digestive Medical Oncology, Cancer Hospital of Shantou University Medical College, Shantou, Guangdong, China.
authors.forename: Xiaowen
authors.initials: X
authors.lastname: Zhuang
mesh_terms: D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics; D019540:Area Under Curve; D015179:Colorectal Neoplasms / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D042943:Dihydrouracil Dehydrogenase (NADP) / Q000378:metabolism; D054796:Drug Dosage Calculations; D016903:Drug Monitoring; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D013940:Thymidylate Synthase / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D000964:Antimetabolites, Antineoplastic; D042943:Dihydrouracil Dehydrogenase (NADP); D013940:Thymidylate Synthase; D005472:Fluorouracil
keywords: area under the plasma concentration-time curve; dihydropyrimidine dehydrogenase; fluorouracil; thymidylate synthetase