FOLFOX6方案中5-氟尿嘧啶稳态血药浓度与个体药理差异及毒性相关性研究

目的:检测接受奥沙利铂+亚叶酸钙+5-氟尿嘧啶(5-Fu)(FOLFOX6)方案化疗的晚期结直肠病人5-Fu血药浓度-时间曲线下面积(AUC),分析AUC在降低不良反应发生率,提高治疗效果方面的相关性.方法:选取以FOLFOX6方案化疗的晚期结直肠癌病人40例,随机分为对照组和观察组,各20例.基于体表面积(BSA)给药,接受2个周期化疗.第1周期所有病人均以传统的BSA给药方式,第2周期开始至化疗结束,对照组仍采用BSA给药方式,观察组在化疗第1周期5-Fu静脉泵入18~30 h内采集外周静脉血测5-Fu血药浓度,并根据5-Fu的AUC调整第2周期用药剂量.2个周期化疗结束后比较2组病人出现的不良反应及疗效情况.结果:2组Ⅰ~Ⅱ级腹泻、胃肠道反应、黏膜炎发生率及Ⅲ~Ⅳ级骨髓抑制、胃肠道反应发生率差异均有统计学意义(P<0.05);2组Ⅰ~Ⅱ级骨髓抑制、手足综合征发生率及Ⅲ~Ⅳ级腹泻、黏膜炎、手足综合征发生率差异均无统计学意义(P>0.05).观察组总体反应率(60.00%)高于对照组的25.00%(P<0.05).结论:实时监测接受FOLFOX6方案化疗的晚期结直肠癌病人5-Fu血药浓度,并根据AUC调整用药剂量,将有效降低不良反应,提高治疗效果.

Study on the correlation between 5-Fu steady-state blood concentration in FOLFOX6 scheme,and individual pharmacological difference and toxicity

Objective:To investigate the plasma concentration of 5-fluorouracil(5-Fu) and area under time curve(AUC) in FOLFOX6oxaliplatin,calcium folinate and 5-Fu scheme treating advanced colorectal cancer,analyze the correlations between AUC,and reducing the incidence of adverse reaction and improving the therapeutic effect.Methods:Forty advanced colorectal cancer patients treated with FOLFOX 6 scheme were randomly divided into the control group and observation group(20 cases each group).Two groups were treated with chemotherapy for two cycles based on body surface area(BSA) administration.The control group was treated with traditional administration mode during two cycles.The observation group was treated with 5-Fu by intravenous infusion for 18 to 30 h in the first cycle,and adjusted dosage of 5-Fu according to the AUC of 5-Fu in the second cycle.The adverse reactions and efficacy between two groups were compared after chemotherapy.Results:The differences of the incidence rates of leveⅠ to Ⅱ diarrhea,gastrointestinal reaction,mucositis and level Ⅲ to Ⅳ myelosuppression between two groups were statistically significant(P<0.05).The differences of the incidence rates of level Ⅰ to Ⅱ myelosuppression,hand-foot syndrome and level Ⅲ to Ⅳ diarrhea between two groups were not statistically significant(P>0.05).The total reaction rate of observation group(60.00%)was higher than the control group(25.00%)(P<0.05).Conclusions:Real-time monitoring the 5-Fu blood concentration in advanced colorectal cancer patients treated with FOLFOX6 chemotherapy and adjusting the dose of 5-Fu according to the AUC can effectively reduce the adverse reaction,and improve the therapeutic effect.