高复发风险肾上腺皮质癌术后米托坦辅助治疗的疗效及安全性  

Efficacy and safety of postoperative adjuvant mitotane therapy in adrenocortical carcinoma at high riskof recurrence

作　　者：刘义 王站 陈嘉洋 邓建华[1] 徐维峰[1] 韩松辰 李亚囡 王旭[1] 赵扬 张玉石[1] Liu Yi;Wang Zhan;Chen Jiayang;Deng Jianhua;Xu Weifeng;Han Songchen;Li Yanan;Wang Xu;Zhao Yang;Zhang Yushi(Department of Urology,Peking Union Medical College Hospital,Chinese Academy of Medical Sciences&Peking Union Medical College,Beijing 100730,China)

机构地区：[1]中国医学科学院北京协和医学院北京协和医院泌尿外科,北京100730

出　　处：《中华泌尿外科杂志》2025年第1期5-9,共5页Chinese Journal of Urology

基　　金：北京协和医院中央高水平医院临床科研专项(2022-PUMCH-B-010);国家资助博士后研究人员计划(GZC20230301)

摘　　要：目的探讨米托坦在高复发风险肾上腺皮质癌(ACC)中的疗效及安全性。方法采用前瞻性观察性研究,筛选2022年9月至2023年11月北京协和医院门诊及住院收治的高复发风险ACC术后患者。符合以下任一条件者为高复发风险:切缘阳性、Ki-67指数>10%、包膜破裂、体积巨大、高级别。所有患者术后3个月内开始米托坦治疗,起始剂量为1.5 g/d,每周增加0.5g,增加至3 g/d后根据血药浓度调整米托坦剂量。所有患者使用米托坦至少1年,用药开始后每12周行1次CT检查评估疗效。主要终点为1年无进展生存率及安全性。采用Kaplan-Meier法进行生存分析,总结治疗相关不良事件。结果本研究共纳入12例。男、女各6例;中位年龄为48(35,51)岁;肿瘤位于左侧8例,右侧3例,双侧1例;患者肾上腺肿瘤欧洲协作组(ENSAT)分期Ⅱ期5例,Ⅲ期7例;肿瘤最大直径为(9.07±2.86)cm;Ki-67指数中位值为(28.9±16.1)%。术后中位31.0(23.0,43.2)d接受米托坦治疗,9例患者血药浓度达到14~20 mg/L。中位随访时间为16.7(12.4,25.2)个月。服用米托坦1年时,10例(83.8%)患者仍处于无疾病进展生存状态;米托坦治疗中位无进展生存时间为27.6个月(95%CI 16.4~未达到)。所有ACC患者使用米托坦后均出现1~2级不良事件;其中1例(8.3%)出现天冬氨酸转氨酶、丙氨酸转氨酶升高及厌食症3级不良事件;所有患者均未出现4~5级不良事件。最常见的不良事件为胃肠道相关症状(10例),包括恶心、呕吐、厌食症、腹泻;其次为肝功能损害(9例)及神经系统毒性(4例)。结论米托坦展现出改善ACC术后高复发风险患者预后的前景,但其具有较大毒性作用,需监测其血药浓度调整用药剂量,同时对不良反应采取措施,以确保患者用药安全。ObjectiveTo explore the efficacy and safety of mitotane in adrenal cortical carcinoma(ACC)at high risk of recurrence.MethodsA prospective observational study was designed from September 2022 to November 2023.ACC patients undergoing surgery with high recurrence risk(positive margin or Ki-67 index>10%or capsule rupture or large size or high-grade ACC)in Peking Union Medical College Hospital were enrolled in this study.All patients started mitotane treatment within 3 months after surgery,with a dose of 1.5 g/d,increased by 0.5 g per week.Once the dose reached 3 g/day,adjustments were made based on blood concentration levels.All patients received mitotane therapy for at least 1 year,and CT was performed every 12 weeks to evaluate the efficacy.The primary endpoint was 1-year progression-free survival(PFS)and safety.The efficacy was analyzed by Kaplan-Meier method for survival,and the occurrence of treatment-related adverse events was summarized.ResultsA total of 12 ACC patients at high risk of recurrence were screened,comprising 6 males and 6 females.Tumors were located on the left side in 8 patients,on the right in 3,and bilaterally in 1.Five patients were classified as ENSAT stageⅡ,while 7 were classified as ENSAT stageⅢ.The maximum diameter of tumor was(9.07±2.86)cm;the median age at diagnosis was 48(35,51)years,and the median Ki-67 index was(28.9±16.1)%.The median time from surgery to initiation of mitotane therapy was 31(23.0,43.2)days,and 9 patients had blood drug concentrations of 14-20 mg/L.The median follow-up time was 16.7(12.4,25.2)months.At 1 year after mitotane therapy,10(83.8%)patients were still in disease-free survival state,with a median mitotane PFS of 27.6 months(95%CI 16.4-not reached).All ACC patients experienced 1-2 grade adverse events after taking mitotane.One patient(8.3%)experienced grade 3 adverse event,including the increasing of alanine aminotransferase and aspartate aminotransferase,as well as anorexia.No grade 4-5 adverse events occurred.The most common adverse events were gastroin

关 键 词：肾上腺皮质肿瘤 癌 米托坦 疗效 安全性 预后 

分 类 号：R736.6[医药卫生—肿瘤]