^(225)Ac-PSMA-617治疗转移性去势抵抗性前列腺癌的安全性和有效性

Safety and efficacy of ^(225)Ac-PSMA-617 in the treatment of metastatic castration-resistant prostate cancer

目的探索^(225)Ac-前列腺特异膜抗原(PSMA)用于转移性去势抵抗性前列腺癌(mCRPC)治疗的安全性和疗效。方法回顾性分析2021年7月至2023年10月在西南医科大学附属医院接受^(225)Ac-PSMA-617治疗的11例mCRPC患者[年龄(70.0±8.8)岁]。采用前列腺癌临床试验工作组3(PCWG3)标准评价治疗前后前列腺特异抗原(PSA)水平的变化以评估疗效。进行治疗前后^(68)Ga-PSMA-11 PET/CT显像, 采用改良后的实体瘤疗效PET评价标准(PERCIST)1.0评估分子影像学反应。采用Kaplan-Meier法分析无进展生存(PFS)和总生存(OS)。采用不良事件通用术语标准5.0版(CTCAE 5.0)进行毒性评估。治疗前后参数比较采用配对t检验或Wilcoxon符号秩检验。结果 11例患者中, 9例患者的PSA水平显著低于治疗前[17.83(4.74, 41.25)与124.33(77.85, 784.22) μg/L;z=-2.67, P=0.008], 其中6例下降>50%;2例患者PSA水平上升>25%, 疾病进展(PD)。^(68)Ga-PSMA-11 PET/CT显像示, 治疗后11例患者中有7例达到基于分子影像的部分缓解(PR);2例达到疾病稳定(SD);2例发生PD。11例患者的OS为12.0(10.0, 18.0)个月, PFS为8.0(6.0, 11.0)个月。所有患者的WBC计数、Hb、PLT、肌酐、肾小球滤过率、丙氨酸氨基转移酶、天冬氨酸氨基转移酶、总胆红素在治疗前后差异均无统计学意义(z值:-1.07~0.00, t值:-0.77~1.76, 均P>0.05)。未发现Ⅲ/Ⅳ级肾脏毒性及唾液腺毒性。结论 ^(225)Ac-PSMA-617是mCRPC有前景的新型治疗选择, 安全性及耐受性良好。

ObjectiveTo evaluate the safety and efficacy of ^(225)Ac-prostate specific membrane antigen(PSMA)in the treatment of metastatic castration-resistant prostate cancer(mCRPC).MethodsEleven patients(age(70.0±8.8)years)with mCRPC who were treated with ^(225)Ac-PSMA-617 between July 2021 and October 2023 in the Affiliated Hospital of Southwest Medical University were retrospectively analyzed.In order to assess efficacy,the Prostate Cancer Clinical Trials Working Group 3(PCWG3)criteria were used to evaluate the changes in prostate specific antigen(PSA)level after the treatment.^(68)Ga-PSMA-11 PET/CT imaging was performed at the baseline and after the treatment,and molecular imaging response was assessed using the modified PET response criteria in solid tumors(PERCIST)1.0.Progression-free survival(PFS)and overall survival(OS)were analyzed using the Kaplan-Meier method.Toxicity was assessed by common terminology criteria for adverse events version 5.0(CTCAE 5.0).The paired t test or Wilcoxon signed rank test was used to compare the parameters before and after treatment.ResultsPost-treatment PSA levels were significantly lower than pre-treatment in 9 of 11 patients(17.83(4.74,41.25)vs 124.33(77.85,784.22)μg/L;z=-2.67,P=0.008),and 6 of them decreasing by more than 50%and 2 patients experienced progressive disease(PD)with PSA levels rising by more than 25%.Post-treatment ^(68)Ga-PSMA-11 PET/CT showed that 7 patients achieved partial response(PR),2 patients achieved stable disease(SD),and 2 patients were with PD.The OS was 12.0(10.0,18.0)months and PFS was 8.0(6.0,11.0)months in 11 patients.There were no statistically significant differences after therapy in WBC counts,Hb,PLT,creatinine,glomerular filtration rate,alanine aminotransferase,aspartate aminotransferase,total bilirubin(z values:from-1.07 to 0.00,t values:from-0.77 to 1.76,all P>0.05).No gradeⅢ/Ⅳnephrotoxicity or salivary gland toxicity was observed.Conclusion ^(225)Ac-PSMA-617 is a promising novel therapeutic option for mCRPC with favorable safety and tolerability.