氟唑帕利治疗转移性去势抵抗性前列腺癌的初步有效性及安全性研究  

Preliminary study on efficacy and safety of fluzoparib in patients with metastatic castration-resistant prostate cancer

作　　者：韦煜 张挺维 何屹 李俊[3] 毕建斌[4] 曾宇[5] 万里军[6] 吴高亮[7] 王焕昇[8] 张军 朱崴 瞿元元 朱耀 叶定伟 WEI Yu;ZHANG Tingwei;HE Yi;LI Jun;BI Jianbin;ZENG Yu;WAN Lijun;WU Gaoliang;WANG Huansheng;ZHANG Jun;ZHU Wei;QU Yuanyuan;ZHU Yao;YE Dingwei(Department of Urology,Fudan University Shanghai Cancer Center,Department of Oncology,Shanghai Medical College,Fudan University,Shanghai 200032,China;Department of Urology,The First Hospital of Jiaxing,Jiaxing 314000,Zhejiang Province,China;Department of Urology,Sichuan Provincial People’s Hospital,Chengdu 610000,Sichuan Province,China;Department of Urology,The First Affiliated Hospital of China Medical University,Shenyang 110001,Liaoning Province,China;Department of Urology,Liaoning Cancer Hospital,Shenyang 110042,Liaoning Province,China;Department of Urology,Quzhou People’s Hospital,Quzhou 324000,Zhejiang Province,China;Department of Urology,Jiangxi Cancer Hospital,Nanchang 330000,Jiangxi Province,China;Department of Urology,Shandong Cancer Hospital,Jinan 250117,Shandong Province,China;Department of Urology,Third Affiliated Hospital,Army Medical University,Chongqing 400030,China)

机构地区：[1]复旦大学附属肿瘤医院泌尿外科,复旦大学上海医学院肿瘤学系,上海200032 [2]嘉兴市第一医院泌尿外科,浙江嘉兴314000 [3]四川省人民医院泌尿外科,四川成都610000 [4]中国医科大学附属第一医院泌尿外科,辽宁沈阳110001 [5]辽宁省肿瘤医院泌尿外科,辽宁沈阳110042 [6]衢州市人民医院泌尿外科,浙江衢州324000 [7]江西省肿瘤医院泌尿外科,江西南昌330000 [8]山东省肿瘤医院泌尿外科,山东济南250117 [9]陆军军医大学第三附属医院泌尿外科,重庆400030

出　　处：《中国癌症杂志》2021年第7期561-566,共6页China Oncology

基　　金：国家自然科学基金面上项目(81872099)。

摘　　要：背景与目的:多聚腺苷二磷酸核糖聚合酶抑制剂[inhibitors of poly(ADP-ribose)polymerase,PARPi]已被多项临床试验证实能使同源重组修复(homologous recombination repair,HRR)基因突变的转移性去势抵抗性前列腺癌(metastatic castration-resistant prostate cancer,mCRPC)患者生存获益。氟唑帕利作为新型PARPi,已获批用于卵巢癌、输卵管癌及腹膜癌的治疗,但尚未见在前列腺癌中的研究报道。初步评价氟唑帕利治疗前列腺癌患者的有效性和安全性。方法:回顾性分析2020年1月1日—2021年2月1日在复旦大学附属肿瘤医院等全国9家医院接受氟唑帕利单药或联合治疗的13例mCRPC患者的临床资料。基因突变数据、生存数据、不良反应等通过门诊随访或电话随访获得。结果:13例患者中,3例行氟唑帕利单药治疗,8例行氟唑帕利联合阿比特龙治疗,2例行氟唑帕利联合雄激素受体拮抗剂SHR3680治疗。单药治疗的3例患者均携带HRR基因突变,且均见前列腺特异性抗原(prostate-specific antigen,PSA)下降,其中2例(66.7%)患者的PSA下降50%以上。氟唑帕利联合阿比特龙治疗的8例患者前期均已阿比特龙耐药,基因检测结果显示,2例患者未携带HRR致病突变,1例患者未接受基因检测,8例患者中仅1例未携带HRR突变的患者接受联合治疗后PSA升高,其余7例(87.5%)患者的PSA下降,3例(37.5%)患者PSA下降50%以上,2例(25.0%)患者PSA下降90%以上。氟唑帕利联合SHR3680治疗的2例患者前期均已阿比特龙及多西他赛耐药,1例患者未接受基因检测且无PSA应答,另1例患者未检测出DNA损伤修复(DNA damage repair,DDR)基因突变但PSA下降50%以上。同时,61.5%(8/13)的患者出现了不同程度的不良反应,主要不良反应为贫血、关节疼痛、食欲下降及乏力;23.1%(3/13)的患者出现了3级贫血,其中1例患者因3级贫血而停止治疗。结论:氟唑帕利单药或联合治疗方案,在mCRPC患者中均显示出一定的�Background and purpose:Inhibitors of poly(ADP-ribose) polymerase(PARPi) has been shown in multiple clinical trials to benefit survival in patients with homologous recombination repair(HRR) gene mutations in metastatic castrationresistant prostate cancer(mCRPC). Fluzoparib has been approved for the treatment of ovarian, fallopian tube and peritoneal cancers, but no data have been reported for prostate cancer. The purpose of this study was to evaluate the efficacy and safety of fluzoparib in the treatment of patients with prostate cancer. Methods:The clinical data of 13 mCRPC patients treated with fluzoparib alone or fluzoparib combined with abiraterone or SHR3680(androgen receptor antagonist) in 9 hospitals nationwide including Fudan University Shanghai Cancer Center from January 1, 2020 to February 1, 2021 were retrospectively analyzed. Genetic mutation data, survival data, adverse reactions and other data were obtained through outpatient cases or telephone follow-up. Results:Among the 13 patients, 3 patients were treated with fluzoparib alone, 8 patients were treated with fluzoparib combined with abiraterone, and 2 patients were treated with fluzoparib combined with SHR3680. All the 3 patients treated with monotherapy carried HRR gene mutations, and all had prostate-specific antigen(PSA);among those, 2 patients(66.7%) had PSA decrease of more than 50%. All the 8 patients treated with fluzoparib combined with abiraterone had been resistant to abiraterone at the earlier stage, and the genetic testing results showed that 2 patients did not carry HRR pathogenic mutation, and 1 patient did not receive genetic testing. Among the 8 patients, only 1 patient without HRR pathogenic mutation had an increase in PSA after receiving the combined treatment, while the remaining 7 patients(87.5%) had a decrease in PSA. PSA decreased by more than 50% in 3 patients(37.5%) and 90% in 2 patients(25.0%). The 2 patients treated with fluzoparib combined with SHR3680 had been resistant to abiraterone and docetaxel at the earlier stage,

关 键 词：前列腺癌 氟唑帕利 同源重组修复缺陷 有效性 

分 类 号：R737.25[医药卫生—肿瘤]