[Relationship between dihydropyrimidine dehydrogenase(DPD) activity and toxicity of 5-FU-based adjuvant chemotherapy in colorectal cancer patients].
OBJECTIVE
The efficacy and toxicity of 5-FU was various in different patients. It was reported that they were correlated to the activity of dihydropyrimidine dehydrogenase (DPD). This study is to measure DPD activity in blood and to analyze the relationship among DPD activity, the toxicity of 5-FU based adjuvant chemotherapy and the 5-FU plasma concentration in colorectal cancer patients.


METHODS
30 colorectal cancer patients were enrolled into the study to receive adjuvant chemotherapy 2 weeks after cured resection. The regimen was 5-FU 425 mg/m(2) plus CF 60 mg/m(2) continuous infused for 2 hours, daily for 5 days. The concentration of endogenous uracil (U) and dihydrouracil (UH(2)) were assayed by high performance liquid chromatography (HPLC). The UH2-U ratio in plasma was used to represent DPD activity in blood. The plasma samples were collected before chemotherapy in all patients to detect the DPD activity in blood, and after 5-FU infusion at day 1 and day 5 to measure 5-FU plasma concentration. The relationship among the DPD activity in blood, the toxicity of chemotherapy and the plasma concentration of 5-FU in all patients were analyzed.


RESULTS
30 colorectal cancer patients have received adjuvant chemotherapy. The DPD activity in the blood of 30 colorectal cancer patients before chemotherapy was 4.09+/-1.21 (2.14-6.7), showed a trend of normal distribution. The 5-FU plasma concentration after 5-FU infusion was (2 079.12+/-621.41) microg/L (1 200.10-3 554.80 microg/L) at the first day, and (2 197.64+/-606.78) microg/L at the fifth day (1 259.00-3 441.03 microg/L). There was a negative relationship between the DPD activity in blood and the 5-FU plasma concentration at day 1 (r=-0.773, P=0.00), and day 5 after 5-FU infusion(r = -0.833, P = 0.00). No significant difference between the 5-FU plasma concentration of day 1 and day 5 was found (P=0.458). The 5-Fu associated toxicities had a negative relationship with DPD activity in blood, and had a positive relationship with 5-FU plasma concentration (P< 0.05).


CONCLUSIONS
The results indicated that the DPD activity in blood can be used to predict the toxicity and the 5-FU plasma concentration in patients with 5-FU based chemotherapy.
Zhou
Zhi-Wei
ZW
Department of Abdominal Surgery, Cancer Center, Sun Yat-sen University, Guangzhou,Guangdong,510060, P.R.China. zhouzhiw@pub.guangzhou.gd.cn
Wang
Guo-Qiang
GQ
Wan
De-Sen
DS
Pan
Zhi-Zhong
ZZ
Li
Su
S
Chen
Gong
G
Liao
Hai
H
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000601:surgery; D042943:Dihydrouracil Dehydrogenase (NADP) / Q000378:metabolism*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects*; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage; D007970:Leukopenia / Q000139:chemically induced; D008297:Male; D008875:Middle Aged; D012004:Rectal Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000601:surgery
D042943:Dihydrouracil Dehydrogenase (NADP); D002955:Leucovorin; D005472:Fluorouracil