Carolina Urologic Research Center, Myrtle Beach, SC.
Chesapeake Urology Research Associates, Towson, MD.
Clin Genitourin Cancer. 2018 Apr;16(2):149-154. doi: 10.1016/j.clgc.2017.10.022. Epub 2017 Nov 7.
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.
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).
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.
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.
美国食品和药物管理局批准了多种去势抵抗性前列腺癌（CRPC）疗法。镭-223 二氯化物（Ra-223）联合醋酸阿比特龙加泼尼松具有不同的作用机制和不同的脱靶副作用特征。我们前瞻性地研究了它们联合使用的安全性、耐受性和患者报告的结果测量指标。
eRADicAte 是一项由研究者发起的、二期临床试验，研究了来自 5 个美国泌尿肿瘤研究机构的 31 例转移性 CRPC 患者。患者接受了 6 个周期的 Ra-223 联合醋酸阿比特龙治疗。使用癌症治疗功能评估-前列腺量表和简明疼痛量表-短表及其子量表评估生活质量和疼痛；我们报告了每个量表达到临床有意义改善标准的患者数量。安全性评估包括东部肿瘤协作组表现状态、实验室变化、阿片类药物使用、影像学反应和不良事件（AE）。
31 例患者中有 20 例（65%）在癌症治疗功能评估-前列腺量表上有阳性的临床有意义的改善，31 例中有 25 例（81%）在前列腺癌子量表上有阳性的改善。31 例中有 18 例（58%）疼痛强度降低，31 例中有 12 例（39%）生活干扰减少。治疗前，患者平均有 11.6±2.8 个骨病变；治疗结束时，患者平均有 5.6±2.4 个骨病变（P=.0002）。最常见的 AE 是腹泻（17%）、恶心（17%）和疲劳（14%）。有 6 例严重 AE，其中 1 例导致研究退出。
患者的生活质量和疼痛得到了有临床意义的改善，且没有出现意外的毒性反应。目前正在进行 Ra-223 联合新型口服激素药物的三期联合试验，以进一步评估影像学进展和总生存获益。
