血药浓度监测指导下伊马替尼减量治疗胃肠间质瘤完整切除术后辅助治疗患者的疗效分析  

Analysis of the efficacy of adjusting the dose of imatinib with therapeutic drug monitoring in adjuvant treatment after complete resection of gastrointestinal stromal tumors

作　　者：陈志亮 田红坤 丁嘉宁 李致颖 毛淦 杜雨强 沈乾 周红 韩勇[2] 曾祥宇[1] 陶凯雄[1] 张鹏[1] Chen Zhiliang;Tian Hongkun;Ding Jianing;Li Zhiying;Mao Gan;Du Yuqiang;Shen Qian;Zhou Hong;Han Yong;Zeng Xiangyu;Tao Kaixiong;Zhang Peng(Department of Gastrointestinal Surgery,Union Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan430022,China;Department of Pharmacy,Union Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan430022,China)

机构地区：[1]华中科技大学同济医学院附属协和医院胃肠外科,武汉430022 [2]华中科技大学同济医学院附属协和医院药剂科,武汉430022

出　　处：《中华胃肠外科杂志》2024年第11期1148-1154,共7页Chinese Journal of Gastrointestinal Surgery

基　　金：国家自然科学基金(81702386、82072736);湖北省自然科学基金(2021CFB566)。

摘　　要：目的探究血药浓度监测指导下伊马替尼减量治疗胃肠间质瘤完整切除术后辅助治疗患者的疗效。方法采用描述性观察性研究方法。纳入标准:(1)手术完整切除且病理诊断为胃肠间质瘤;(2)术后行伊马替尼辅助治疗且存在剂量调整;(3)多次行伊马替尼血药浓度监测;(4)临床病理资料及随访资料完整。回顾性收集2015年1月至2023年12月于华中科技大学同济医学院附属协和医院就诊的70例胃肠间质瘤病例资料。男性15例(21.4%),女性55例(78.6%);中位年龄60(25~82)岁;高危患者49例(70.0%),中危患者14例(20.0%),低危患者6例(8.6%),1例(1.4%)患者行伊马替尼术前治疗。患者每2~3个月至胃肠间质瘤专病门诊复查血药浓度。基于血药浓度监测下,综合患者不良反应是否≥Ⅲ级、首次血药谷浓度是否≥1500μg/L以及是否在血药浓度期望区间(760~1100μg/L),将剂量调整为300 mg/d或200 mg/d。观察指标包括剂量调整前后本组患者的不良反应、生活质量情况、以及剂量调整后总体生存期(OS)和无复发生存期(RFS)。结果剂量调整前,70例患者每日服药剂量均为400 mg,首次血药谷浓度水平为(1900±568)μg/L,剂量调整前服药时长中位数为8.3个月。剂量调整后,60例患者每日服用剂量为300 mg,血药谷浓度水平为(1216±350)μg/L;10例患者服用剂量为200 mg,血药谷浓度水平为(1023±269)μg/L,剂量调整后服药中位时长为23.4个月。伊马替尼剂量调整后,全组患者骨髓抑制减少[74.3%(52/70)比51.4%(36/70),χ^(2)=9.202,P=0.010];水肿减少[95.7%(67/70)比50.0%(35/70),χ^(2)=40.526,P<0.001];皮肤反应减少[70.0%(49/70)比32.9%(23/70),χ^(2)=22.495,P<0.001];消化道反应减少[38.6%(27/70)比10.0%(7/70),χ^(2)=15.899,P<0.001],差异均有统计学意义(均P<0.05)。剂量调整前后患者躯体健康总测量评分分别为(76±5)和(88±4)分,心理健康总测量评分分别为(75±6)和(89±4)分。全组患者中位随访36(6~126)个Objective To explore the efficacy of adjusting the dose of imatinib dose in the context of therapeutic drug monitoring(TDM)in patients with gastrointestinal stromal tumors(GISTs)who are receiving adjuvant therapy after complete resection of their tumors.Methods This was a descriptive study.Inclusion criteria were(1)complete surgical resection with a pathological diagnosis of GIST,(2)postoperative adjuvant therapy with imatinib and dosage adjustment,(3)multiple TDM of imatinib,and(4)complete clinical,pathological,and follow-up data.The data of 70 patients with GISTs treated at Union Hospital,Tongji Medical College,Huazhong University of Science and Technology between January 2015 and December 2023 were collected retrospectively.The study cohort comprised 15(21.4%)men and 55(78.6%)women of median age 60 years(range:25-82).Of the eligible patients,49(70.0%)were at high-risk,14(20.0%)at intermediate-risk,six(8.6%)at low-risk,and one(1.4%)at very low risk.Patients were followed up by the gastrointestinal stromal tumor clinic every 2-3 months and their plasma concentrations of imatinib were checked.The dose was adjusted to 300 mg/d or 200 mg/d depending on whether they had had≥grade III adverse reactions,and whether the first plasma concentration of imatinib was≥1,500μg/L or between the expected range of 760μg/L-1,100μg/L.Studied indicators included adverse reactions,quality of life before and after dose adjustment,and overall survival and recurrence-free survival(RFS)after dose adjustment.Results Before dose adjustment,all 70 patients received 400 mg of imatinib daily,with initial TDM values of 1,900±568μg/L,for a median duration of 8.3 months.After dose adjustment,60 patients received 300 mg daily,with a TDM of 1,216±350μg/L,whereas 10 received 200 mg daily,with a TDM of 1,023±269μg/L.The median duration of treatment after dose adjustment was 23.4 months.Compared with those whose dosages were not adjusted,the incidence of bone marrow suppression was significantly lower(74.3%[52/70]vs.51.4%[36/70],χ^(2)=

关 键 词：胃肠间质瘤 伊马替尼 不良反应 剂量调整 血药浓度 生活质量 

分 类 号：R735[医药卫生—肿瘤]