eRADicAte: A Prospective Evaluation Combining Radium-223 Dichloride and Abiraterone Acetate Plus Prednisone in Patients With Castration-Resistant Prostate Cancer
eRADicAte: A Prospective Evaluation Combining Radium-223 Dichloride and Abiraterone Acetate Plus Prednisone in Patients With Castration-Resistant Prostate Cancer
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DOI：
10.1016/j.clgc.2017.10.022
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发表时间：
2018-04-01
影响因子：
3.2
通讯作者：
Harrelson, Stacey S.
中科院分区：
文献类型：
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作者：
Shore, Neal D.;Tutrone, Ronald F.;Harrelson, Stacey S.
这是第一项前瞻性评估镭-223二氯化物和一种新型口服激素治疗醋酸阿比特龙联合治疗转移性去势抵抗性前列腺癌的研究。eRADicAte研究表明，转移性去势抵抗性前列腺癌患者的生活质量得到了临床意义上的改善，疼痛减轻，骨病变减少，安全性和毒性可接受。背景：多种去势抵抗性前列腺癌（CRPC）疗法已被美国食品和药物管理局批准。二氯化镭-223（Ra-223）与醋酸阿比特龙加泼尼松具有不同的作用机制和明显的脱靶副作用特征。我们前瞻性地研究了它们的联合安全性、耐受性和患者报告的结局指标。患者和方法：eRADicAte是一项由化疗药物启动的II期试验，研究了来自5个美国泌尿肿瘤研究中心的31例转移性CRPC患者。患者完成了6个周期的Ra-223联合阿比特龙治疗。使用癌症治疗功能评估-前列腺和简明疼痛量表-简表问卷及其子量表评估生活质量和疼痛;我们报告了符合每个量表有临床意义改善的标准化标准的受试者人数。安全性评估包括东部肿瘤协作组的体能状态、实验室变化、阿片类药物使用、影像学反应和不良事件（AE）。结果如下：20/31（65%）例患者在癌症治疗功能评估-前列腺方面出现了积极的有临床意义的改善变化，25/31（81%）例患者在前列腺癌子量表方面出现了积极的有临床意义的改善变化。31例患者中有18例（58%）表现出疼痛强度降低，31例患者中有12例（39%）表现出疼痛干扰减少。基线时，受试者平均有11.6 +/- 2.8处骨病变;治疗结束时，受试者平均有5.6 +/- 2.4处骨病变（P=.0002）。最常见的AE为腹泻（17%）、恶心（17%）和疲乏（14%）。有6起严重AE; 1起导致退出研究。结论：患者在生活质量和疼痛方面经历了具有临床意义的改善，没有意外的不良反应。Ra-223与新型口服激素药物的III期联合试验正在进行中，以进一步评估放射学进展和总生存期获益。(C)2017作者（S）爱思唯尔公司出版
This is the first study to prospectively evaluate the combined use of radium-223 dichloride and a novel oral hormonal therapy, abiraterone acetate, in men with metastatic castration-resistant prostate cancer. The eRADicAte study showed that patients with metastatic castration-resistant prostate cancer experienced clinically meaningful improvements in quality of life with decreased pain, reduction in bone lesions, and an acceptable safety and toxicity profile.Background: Multiple castration-resistant prostate cancer (CRPC) therapies are approved by the United States Food and Drug Administration. Radium-223 dichloride (Ra-223) with abiraterone acetate plus prednisone have different mechanisms of action and distinct off-target side-effect profiles. We prospectively investigated their combined safety, tolerability, and patient-reported outcome measures. Patients and Methods: eRADicAte, an investigator-initiated, phase II trial, studied 31 patients with metastatic CRPC, from 5 United States uro-oncology research sites. Patients completed 6 cycles of Ra-223 with concurrent abiraterone therapy. Quality of life and pain were assessed using the Functional Assessment of Cancer Therapy-Prostate and the Brief Pain Inventory-Short Form questionnaires and their subscales; we reported the number of subjects meeting standardized criteria for clinically meaningful improvements on each scale. Safety assessment included Eastern Cooperative Oncology Group performance status, laboratory changes, opioid use, radiographic responses, and adverse events (AEs). Results: Twenty of 31 (65%) experienced positive clinically meaningful improvement changes on the Functional Assessment of Cancer Therapy-Prostate, and 25 (81%) of 31 on the Prostate Cancer Subscale. Eighteen (58%) of 31 demonstrated reduced pain intensity and 12 (39%) of 31 demonstrated reduction of pain interference in their lives. At baseline, subjects averaged 11.6 +/- 2.8 bone lesions; at the end of treatment, subjects averaged 5.6 +/- 2.4 bone lesions (P=.0002). The most frequent AEs were diarrhea (17%), nausea (17%), and fatigue (14%). There were 6 serious AEs; 1 led to study withdrawal. Conclusions: Patients experienced clinically meaningful improvements in quality of life and pain, without unexpected adverse toxicities. Phase III combination trials of Ra-223 with novel oral hormonal agents are ongoing to further evaluate radiographic progression and overall survival benefit. (C) 2017 The Author(s). Published by Elsevier Inc.