Correlation Of Pharmacokinetic Parameter AUC With Adverse Reaction And Short-term Effect Of 5-fluorouracil In Patients With Advanced Colorectal Cancer

ObjectiveTo investigate the relationship between pharmacokinetic parameter of 5-fluorouracil(5-FU)area under the curve drug concentration-time(AUC)and adverse reactions as well as therapeutic efficacy in patients with advanced colorectal cancer receiving chemotherapy regimen of m FOLFOX6(oxaliplatin plus calcium folinate and fluorouracil) by detecting pharmacokinetic parameter AUC and provide theoretical basis for clinical individual therapy. MethodsSixty-two patients with advanced colorectal cancer from 2014 to 2015 in the department of oncology, the People’s Hospital of Zhengzhou University, were given chemotherapy with standard m FOLFOX6, two weeks as one cycle. Blood samples were collected after 18-30 hours of infusion of 5-FU in the first cycle to detect the plasma concentration of 5-FU and calculate the pharmacokinetic parameter AUC value. The effect and adverse reactions of chemotherapy were evaluated after 2 cycles. The incidence of adverse reactions were analyzed in AUC≤25(mg·h)/L group and >25(mg·h)/L group, and the effect was compared between the AUC≤20(mg·h)/L group and >20(mg·h)/L group. Results(1) the pharmacokinetic parameter AUC of 5-FU in 62 patients with advanced colorectal cancer was normally distributed, ranging from 5.2 to 39.1(mg·h)/L, with the average and median level of 21.26 and 22.20(mg·h)/L. There were 25 patients with AUC >25(mg·h)/L, 12 patients with AUC 20 to 25(mg·h)/L and 25 patients with AUC≤20(mg·h)/L.(2) The incidence of myelotoxicity, diarrhea and mucoxitis in III-IV level were significantly lower in AUC≤25(mg·h)/L group(11%, 5%, 8%) than those in AUC>25(mg·h)/L group(44%, 28%, 32%)(P<0.05).(3)The complete remission rate was significantly lower effective rate in AUC≤20(mg·h)/L group(32.0%) than that in AUC>20(mg·h)/L group(59.5%)(P<0.05). ConclusionWhen the pharmacokinetic parameter AUC of 5-FU maintains from 20 to 25(mg·h)/L, the patients with advanced colorectal cancer receiving chemotherapy regimen of m FOLFOX6 will obtain optimal response rate and less toxicities.