晚期结直肠癌患者5-氟尿嘧啶理想血药浓度-时间曲线下面积区间值研究

Research on the Interval Value of Area Under the Curve of Ideal Blood Concentration-Time of 5-Fluorouracil in Patients with Advanced Colorectal Cancer

目的:探讨晚期结直肠癌(colorectal cancer,CRC)患者应用5-氟尿嘧啶(5-FU)为基础化疗时,5-FU理想血药浓度-时间曲线下面积(AUC)的区间值。方法:本研究纳入2017年8月至2018年6月哈尔滨医科大学附属肿瘤医院收治的应用5-FU为基础化疗方案治疗的晚期CRC患者49例,5-FU的给药剂量根据患者的体表面积(BSA)确定。利用超高效液相色谱-串联质谱技术测定CRC患者应用5-FU持续静脉滴注18~30 h的5-FU稳态血药浓度(CSS),准确记录患者使用5-FU的滴注开始时间及结束时间,计算患者持续滴注时间(TCI),根据AUC=CSS×TCI计算患者AUC值。同时对患者的治疗效果及不良反应进行评价,分析CRC患者5-FU AUC与疗效和不良反应的关系,探讨5-FU在结直肠癌治疗中的理想AUC范围。结果:5-FU的CSS范围为180~880 ng/ml;5-FU AUC呈非正态分布,范围为8.43~41.1 mg·h/L,均值为(19.01±7.32) mg·h/L,AUC具有明显个体间差异,可达5倍;相关性分析结果提示,5-FU AUC与临床疗效、不良反应之间存在明显相关性。5-FU理想AUC范围是21.75~28.63 mg·h/L。结论:晚期CRC患者基于BSA确定5-FU给药剂量,5-FU的AUC存在明显的个体差异,5-FU理想AUC区间为21.75~28.63 mg·h/L。

OBJECTIVE: To probe into the interval value of area under the curve( AUC) of ideal blood concentration-time of 5-fluorouracil( 5-FU) when patients with advanced colorectal cancer( CRC) were receiving5-FU based chemotherapy. METHODS: Totally 49 patients with advanced CRC receiving 5-FU based chemotherapy from Aug. 2017 to Jun. 2018 in Harbin Medical University Cancer Hospital were involved in this study,the dosage of5-FU was determined according to the patient’s body surface area( BSA). Using ultra-high performance liquid chromatography-tandem mass spectrum technology to determine the 5-FU steady-state blood concentration( CSS) in CRC patients receiving 5-FU in continuous intravenous infusion for 18-30 h,the start time and end time of 5-FU infusion in patients were accurately recorded,the continuous infusion time( TCI) was calculated,and the AUC value was calculated according to AUC = CSS× TCI. At the same time,the treatment effect and adverse drug reactions of patients were evaluated,in order to analyze the relationship between 5-FU AUC and efficacy and adverse drug reactions in CRC patients,and explore the ideal AUC range of 5-FU in the treatment of colorectal cancer. RESULTS: The CSS range of 5-FU was 180-880 ng/ml;the AUC of 5-FU presented an abnormal distribution,ranging from 8. 43 to41. 1 mg·h/L,with an average value of 19. 01 ± 7. 32 mg·h/L,and the AUC value had obvious inter-individual differences up to 5 times. Correlation analysis results revealed that there was a significant correlation between AUC of5-FU and clinical efficacy and adverse drug reactions. The ideal AUC range of 5-FU was 21. 75-28. 63 mg·h/L.CONCLUSIONS: There are obvious individual differences in AUC value in CRC patients receiving different dosages of5-FU based on BSA. The ideal AUC interval value of 5-FU is 21. 75-28. 63 mg·h/L.