The Institute of Cancer Research and Royal Marsden Hospital, London, UK.
Urology San Antonio, San Antonio, TX, USA.
Eur Urol. 2020 Aug;78(2):184-192. doi: 10.1016/j.eururo.2020.03.001. Epub 2020 Apr 6.
External beam radiotherapy (EBRT) with neoadjuvant/adjuvant androgen deprivation therapy (ADT) is an established treatment option to prolong survival for patients with intermediate- and high-risk prostate cancer (PCa). Relugolix, an oral gonadotropin-releasing hormone (GnRH) receptor antagonist, was evaluated in this clinical setting in comparison with degarelix, an injectable GnRH antagonist.
To evaluate the safety and efficacy of relugolix to achieve and maintain castration.
DESIGN, SETTING, AND PARTICIPANTS: A phase 2 open-label study was conducted in 103 intermediate-risk PCa patients undergoing primary EBRT and neoadjuvant/adjuvant ADT between June 2014 and December 2015.
Patients randomly assigned (3:2) to 24-wk treatment with either daily oral relugolix or 4-wk subcutaneous depot degarelix (reference control).
The primary endpoint was the rate of effective castration (testosterone <1.73nmol/l) in relugolix patients between 4 and 24 wk of treatment. Secondary endpoints included rate of profound castration (testosterone <0.7nmol/l), prostate-specific antigen (PSA) levels, prostate volume, quality of life (QoL) assessed using the Aging Males' Symptoms scale, and the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life (30-item EORTC core questionnaire [EORTC QLQ-C30] and 25-item EORTC prostate cancer module [EORTC QLQ-PR25]) questionnaires, and safety. No formal statistical comparisons with degarelix were planned.
Castration rates during treatment were 95% and 82% with relugolix and 89% and 68% with degarelix for 1.73 and 0.7nmol/l thresholds, respectively. Median time to castration in the relugolix arm was 4 d. During treatment, PSA levels and prostate volumes were reduced in both groups. Three months after discontinuing treatment, 52% of men on relugolix and 16% on degarelix experienced testosterone recovery (statistical significance of differences not tested). Mean and median QoL scores improved following treatment discontinuation. The most common adverse event was hot flush (relugolix 57%; degarelix 61%). Lack of blinding was a potential limitation.
Relugolix achieved testosterone suppression to castrate levels within days and maintained it over 24 wk with a safety profile consistent with its mechanism of action.
Oral once-daily relugolix may be a novel oral alternative to injectable androgen deprivation therapies.
外照射放射治疗（EBRT）联合新辅助/辅助去势治疗（ADT）是一种延长中高危前列腺癌（PCa）患者生存时间的既定治疗选择。在这种临床环境下，口服促性腺激素释放激素（GnRH）受体拮抗剂瑞戈非尼与注射 GnRH 拮抗剂地加瑞克进行了评估。
评估瑞戈非尼实现和维持去势的安全性和有效性。
设计、地点和参与者：一项开放标签的 2 期研究纳入了 2014 年 6 月至 2015 年 12 月期间 103 例接受原发 EBRT 和新辅助/辅助 ADT 的中危 PCa 患者。
患者被随机分配（3:2）接受为期 24 周的每日口服瑞戈非尼或 4 周皮下 depot 地加瑞克（参考对照）治疗。
主要终点是瑞戈非尼治疗 4 至 24 周时有效去势（睾酮<1.73nmol/l）的发生率。次要终点包括深度去势（睾酮<0.7nmol/l）、前列腺特异性抗原（PSA）水平、前列腺体积、使用衰老男性症状量表（Aging Males' Symptoms scale）评估的生活质量（QoL）以及欧洲癌症研究与治疗组织（EORTC）生活质量（30 项 EORTC 核心问卷[EORTC QLQ-C30]和 25 项 EORTC 前列腺癌模块[EORTC QLQ-PR25]）问卷以及安全性。未计划与地加瑞克进行正式的统计学比较。
瑞戈非尼和地加瑞克的 1.73 和 0.7nmol/l 阈值的去势率分别为 95%和 82%，89%和 68%。瑞戈非尼组的中位去势时间为 4 天。治疗期间，两组的 PSA 水平和前列腺体积均降低。治疗停止后 3 个月，瑞戈非尼组有 52%的男性和地加瑞克组有 16%的男性经历了睾酮恢复（未测试差异的统计学意义）。治疗停止后，平均和中位 QoL 评分均有所改善。最常见的不良事件是热潮红（瑞戈非尼 57%；地加瑞克 61%）。缺乏盲法是一个潜在的限制。
瑞戈非尼在数天内将睾酮抑制至去势水平，并在 24 周内维持该水平，其安全性与其作用机制一致。
口服瑞戈非尼可能是一种新型的口服雄激素剥夺治疗替代方案。
