泼尼松转换为地塞米松治疗mCRPC的疗效分析  

Switch from prednisone to dexamethasone in metastatic castration-resistant prostate cancer patients progressing on abiraterone plus prednisone

作　　者：杨振宇 叶阳天 李志勇 李永红[1] 蒋丽娟[1] 陈东[1] 吴志明[1] 王延军[1] 何立儒[2] 史艳侠[3] '周芳坚[1] Yang Zhenyu;Ye Yangtian;Li Zhiyong;Li Yonghong;Jiang Lijuan;Chen Dong;Wu Zhiming;Wang Yanjun;He Liru;Shi Yanxia;Zhou Fangjian(Department of Urology,Sun Yat-sen University Cancer Center,Guangzhou 510060,China;Department of Radiation Oncology,Sun Yat-sen University Cancer Center,Guangzhou 510060,China;Department of Medical Oncology,Sun Yat-sen University Cancer Center,Guangzhou 510060,China;Department of Urology,the First Affiliated Hospital of Jinan University,Guangzhou 510630,China)

机构地区：[1]中山大学肿瘤防治中心泌尿外科,广州510060 [2]中山大学肿瘤防治中心放疗科,广州510060 [3]中山大学肿瘤防治中心肿瘤内科,广州510060 [4]暨南大学附属第一医院泌尿外科,广州510630

出　　处：《中华泌尿外科杂志》2020年第8期597-602,共6页Chinese Journal of Urology

基　　金：国家自然科学基金(81772726);广东省自然科学基金(2016A030310213)。

摘　　要：目的评估转移性去势抵抗性前列腺癌(mCRPC)患者接受阿比特龙联合泼尼松治疗(AA+P)出现进展后,更改为阿比特龙联合地塞米松(AA+D)治疗的疗效和安全性。方法回顾性分析2016年11月至2019年12月在中山大学肿瘤防治中心接受AA+P治疗出现进展、改为AA+D治疗的46例mCRPC患者的临床资料。中位年龄72岁(50~89岁),雄激素剥夺治疗(ADT)敏感中位时间14.6个月(2.1~168.5个月)。初诊时、开始AA+P治疗时、皮质激素转换时患者的中位PSA水平分别为258.9 ng/ml(10.0~11640.0 ng/ml)、56.6 ng/ml(3.6~1348.0 ng/ml)、25.1 ng/ml(2.2~933.6 ng/ml)。伴骨转移42例,淋巴结转移12例,内脏转移7例。28例Gleason评分≥8分,11例Gleason评分<8分,7例Gleason评分不详。主要研究终点为肿瘤无进展生存时间(PFS),次要研究终点包括前列腺特异性抗原(PSA)下降≥50%和30%的反应率以及安全性。根据患者接受AA+P治疗的PFS和皮质激素转换时的PSA水平对患者进行风险分层。结果46例接受AA+D治疗的患者中位随访时间4.9个月(2.0~24.1个月),至末次随访时40例出现进展,1例因脑梗死停止治疗,5例仍在接受AA+D治疗。所有患者治疗耐受性良好,无3级和4级不良反应。中位PFS为3.7个月(1.6~24.1个月)。12例(26.1%)接受AA+D治疗后PSA下降≥50%,21例(45.7%)PSA下降≥30%。PSA下降≥50%和PSA未下降≥50%的患者中位PFS分别为8.5个月(2.7~24.1个月)和3.0个月(1.6~17.8个月)。单因素分析结果提示以下4个指标与皮质激素转换后AA+D治疗较长的PFS有关:皮质激素转换时较低的PSA水平(<30 ng/ml,HR=0.30,95%CI 0.14~0.64,P=0.002),ADT敏感时间(≥18个月,HR=0.55,95%CI 0.28~1.06,P=0.045),较长的AA+P治疗PFS(≥8个月,HR=0.36,95%CI 0.18~0.72,P=0.004),AA+D治疗PSA较大的下降幅度(≥50%,HR=0.30,95%CI 0.17~0.75,P=0.007)。多因素分析结果提示上述4个指标是AA+D治疗PFS预后良好的独立因素(均P<0.05)。结论mCRPC患者接受AA+P治疗出现进展后,泼尼Objective To evaluate the efficacy and safety of switch from prednisone(AA+P)to dexamethasone(AA+D)in metastatic castration-resistant prostate cancer patients(mCRPC)progressing on abiraterone plus prednisone.Methods Between November 2016 and December 2019,46 mCRPC patients were switched to AA+D after progression on AA+P at Sun Yet-sen University Cancer center.Median age was 72 years(50 to 89 years),with median androgen deprivation therapy(ADT)duration 14.6 months(2.1 to 168.5 months).PSA level at the time of diagnosis,the initiation of AA+P treatment,the time of switch were 258.9 ng/ml,56.6 ng/ml,25.1 ng/ml,respectively.42(91.3%),12(26.1%),7(15.2%)patients had bone metastasis,lymph node metastasis,visceral metastasis,respectively.28 patients had Gleason score≥8,and 11 patients had Gleason score<8.The primary endpoint was progression free-survival(PFS).Secondary endpoints included PSA response rate of PSA decline≥50% and≥30% and safety.Patients were divided into different risk level groups according to PSA level at the time of switch and PFS on AA+P.Results The median follow-up of 46 patients was 4.9 months,40 patients progressed at the last follow-up,the treatment was terminated in 1 patient because of cerebral infarction,5 patients were still on the treatment of AA+D.Median PFS on AA+D of 46 patients was 3.7(1.6-24.1)months.A total of 12(26.1%)patients showed a PSA decline≥50%after treatment with AA+D,and 21(45.7%)patients showed a PSA decline≥30%.The median PFS was 8.5(2.7-24.1)and 3.0(1.6-17.8)months for patients with PSA decline≥50% and PSA didn’t decline≥50%,respectively.Four factors below were significantly associated with a longer PFS on AA+D after steroid switch in univariate analysis:lower PSA level at the time of switch(<30 ng/ml,HR=0.30,95%CI 0.14-0.64,P=0.002),longer ADT sensitivity duration(≥18 months,HR=0.55,95%CI 0.28-1.06,P=0.045),longer AA+P treatment PFS(≥8 months,HR=0.36,95%CI 0.18-0.72,P=0.004),and greater PSA decline on AA+D(≥50%,HR=0.30,95%CI 0.17-0.75,P=0.007).The abov

关 键 词：前列腺肿瘤 转移性 去势抵抗性 阿比特龙 泼尼松 地塞米松 

分 类 号：R737.25[医药卫生—肿瘤]