摘要
目的多西他赛广泛应用于多种癌症治疗,但由于其个体药代动力学差异较大和治疗窗狭窄,个体间疗效和不良反应差异较大。本研究探讨晚期食管癌患者应用多西他赛联合奈达铂方案化疗过程中,进行治疗药物监测的意义。方法收集2014-07-01-2015-12-31南通大学附属肿瘤医院晚期食管癌患者72例,给予多西他赛75mg/m2,静脉滴入d1;奈达铂80mg/m2,静脉滴入d1,21d为1个周期。多西他赛静脉滴入结束前10min和静脉滴入结束后30~60min各采集静脉2mL,采用胶乳免疫比浊法检测血药浓度,对血药浓度结果进行药代动力学分析,得出血药浓度-时间曲线下面积(area under concentration-time curve,AUC)。根据多西他赛AUC值,分为高AUC组、正常范围AUC组和低AUC组。比较3组近期疗效,每2个周期结束评价近期疗效,并观察不良反应发生情况。结果 3组有效率、临床获益率差异均无统计学意义,P>0.05。低AUC组Ⅲ+Ⅳ级白细胞减少发生率为11.76%,低于正常范围AUC组的42.86%,P=0.033;高AUC组Ⅲ+Ⅳ级血小板减少发生率为61.54%,明显高于正常范围AUC组23.81%,P=0.020。较正常范围AUC组贫血发生率52.27%,高AUC组贫血发生率(92.31%)明显升高,P=0.015。而恶心呕吐、口腔炎和体液潴留等不良反应发生率比较差异无统计学意义,P>0.05。结论多西他赛药代动力学参数AUC与晚期食管癌患者多西他赛联合奈达铂化疗所致血液学毒性严重程度密切相关,进行治疗药物监测值得在临床推广和应用。
OBJECTIVE Although docetaxel is highly effective in cancer treatment,its use is associated with serious complications attributable to large interindividual variability in pharmacokinetics and a narrow therapeutic window.Therefore,we evaluated the effect of therapeutic drug monitoring on the efficacy and toxicity,given the chemotherapy of docetaxel combined with nedaplatin.METHODS Seventy-two advanced esophageal cancer patients were recruited from the Affiliated Tumor Hospital to Nantong University from 1July 2014 to 31December 2015.Patients received intravenous injection of 75mg/m～2 docetacel by day 1,and 80mg/m～2 nedaplatin by day 1,for 21 days as one cycle.Plasma concentration of docetacel was measured by immunoturbidimetry.Two mL vein blood was obtained 10 minutes before,and30 to 60minutes after intravenous injection of docetacel,respectively.The pharmacokinetic data as area under concentration-time curve（AUC）and toxicity data were recorded.Patients were divided into three groups according to AUC.RESULTS There were no statistical significances in the response rates and clinical benefit rates in the three groups.The incidence of leucopeniaⅢtoⅣ was 11.76%in low AUC group,significantly lower in high AUC group than in the normal range AUC group 42.86%（P=0.033）.The incidences of thrombocytopeniaⅢtoⅣ and anemia were higher than that in the normal range AUC group,respectively（P=0.020,P=0.015）.There were no statistical significances in the incidences of nausea and vomiting,stomatitis and fluid retention.CONCLUSIONS Individual exposure to docetaxel is variable and predictive of high grade hematologic toxicity.The therapeutic drug monitoring of docetacel was useful and safe for estimating the individual dose in advanced esophageal cancer in the Chinese population.
出处
《中华肿瘤防治杂志》
CAS
北大核心
2017年第3期192-195,共4页
Chinese Journal of Cancer Prevention and Treatment
基金
江苏省药学会-奥赛康临床药学基金(201515)
南通市卫生局青年科研基金(WQ2014042)
