The dihydrouracil/uracil ratios in plasma and toxicities of 5-fluorouracil-based adjuvant chemotherapy in colorectal cancer patients.
BACKGROUND
This study was designed to measure the dihydrouracil (UH(2))/uracil (U) ratio in plasma as a surrogate marker for dihydropyrimidine dehydrogenase (DPD) activity and to investigate the relationships of the UH(2)/U ratios in plasma with the toxicities of 5-fluorouracil (5-FU)-based adjuvant chemotherapy and 5-FU plasma concentrations in colorectal cancer patients.


METHODS
Thirty colorectal cancer patients received adjuvant chemotherapy of leucovorin plus 5-FU after operations. The concentrations of UH(2), U and 5-FU were assayed by the high-performance liquid chromatography method. The relationships of the UH(2)/U ratios with the 5-FU toxicities and 5-FU plasma concentrations were analyzed.


RESULTS
There was a negative relationship between the UH(2)/U ratios and 5-FU plasma concentrations (p <0.001). 5-FU toxicities had a negative correlation with the UH(2)/U ratios and a positive correlation with 5-FU plasma concentrations (p < 0.05).


CONCLUSIONS
The UH(2)/U ratio in plasma has close correlations with the 5-FU plasma concentration and 5-FU toxicity during chemotherapy, which may highlight the theoretical base of individual therapy for patients with colorectal cancer.
Zhou
Zhi Wei
ZW
Department of Abdominal Surgery, State Key Laboratory of Oncology in Southern China, Cancer Center, Sun Yat-sen University, Guangzhou, China.
Wang
Guo Qiang
GQ
Wan
De Sen
de S
Lu
Zhen Hai
ZH
Chen
Ying Bo
YB
Li
Su
S
Chen
Gong
G
Pan
Zhi Zhong
ZZ
D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use; D017024:Chemotherapy, Adjuvant; D015179:Colorectal Neoplasms / Q000097:blood* / Q000188:drug therapy; D005260:Female; D005472:Fluorouracil / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use; D006801:Humans; D002955:Leucovorin / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D014498:Uracil / Q000031:analogs & derivatives* / Q000097:blood*; D014803:Vitamin B Complex / Q000627:therapeutic use
D000964:Antimetabolites, Antineoplastic; C007419:dihydrouracil; D014803:Vitamin B Complex; D014498:Uracil; D002955:Leucovorin; D005472:Fluorouracil