一项评估瑞戈非尼联合新型激素疗法治疗晚期前列腺癌的安全性和剂量的 I 期临床试验。
A Phase I Clinical Trial Evaluating the Safety and Dosing of Relugolix with Novel Hormonal Therapy for the Treatment of Advanced Prostate Cancer.
机构信息
Urology San Antonio, 3327 Research Plaza Suite 403, San Antonio, TX, 78235, USA.
Arizona Urology Specialists, Tucson, AZ, USA.
出版信息
Target Oncol. 2023 May;18(3):383-390. doi: 10.1007/s11523-023-00967-5. Epub 2023 Apr 15.
BACKGROUND
Androgen deprivation therapy (ADT), a cornerstone of prostate cancer treatment, is commonly co-prescribed as combination therapy.
OBJECTIVE
To better understand the safety and tolerability profile of relugolix, an oral non-peptide gonadotropin-releasing hormone (GnRH) receptor antagonist, in combination with abiraterone acetate (abiraterone) and apalutamide, a phase I study was undertaken.
PATIENTS AND METHODS
This is an ongoing, 52-week, open-label, parallel cohort study of relugolix in combination with abiraterone in men with metastatic castration-sensitive prostate cancer (mCSPC) or metastatic castration-resistant prostate cancer (mCRPC) [Part 1] and apalutamide in men with mCSPC or non-metastatic castration-resistant prostate cancer (nmCRPC) [Part 2]. Eligible patients treated with leuprolide acetate or degarelix with abiraterone or apalutamide prior to baseline, at which time they were transitioned to relugolix. Assessments included reporting of adverse events, clinical laboratory tests, vital sign measurements, electrocardiogram (ECG) parameters, and testosterone serum concentrations. In this interim report, patients completing ≥12 weeks were included.
RESULTS
Overall, 15 men were enrolled in Part 1 and 10 in Part 2. Adverse events were mostly mild-to-moderate in intensity and were consistent with the known safety profiles of the individual medications. No transition (from prior ADT treatment)- or time-related trends in clinical laboratory tests, vital sign measurements, or ECG parameters were observed. Mean testosterone concentrations remained below castration levels.
CONCLUSIONS
Combination therapy of relugolix and abiraterone or apalutamide was associated with a favorable safety and tolerability profile consistent with the known profiles of the individual medications. Castration levels of testosterone were maintained after transitioning to relugolix from other ADTs.
CLINICAL TRIAL REGISTRATION
ClinicalTrials.gov identifier: NCT04666129.
背景
去势治疗（ADT）是前列腺癌治疗的基石，通常联合治疗。
目的
为了更好地了解口服非肽类促性腺激素释放激素（GnRH）受体拮抗剂瑞戈非尼与醋酸阿比特龙（阿比特龙）和阿帕鲁胺联合应用的安全性和耐受性概况，进行了一项 I 期研究。
患者和方法
这是一项正在进行的、52 周、开放标签、平行队列研究，评估瑞戈非尼联合阿比特龙治疗转移性去势敏感前列腺癌（mCSPC）或转移性去势抵抗性前列腺癌（mCRPC）的男性[第 1 部分]和阿帕鲁胺治疗 mCSPC 或非转移性去势抵抗性前列腺癌（nmCRPC）的男性[第 2 部分]。符合条件的患者在基线时接受醋酸亮丙瑞林或地加瑞克联合阿比特龙或阿帕鲁胺治疗，此时他们转为瑞戈非尼治疗。评估包括不良事件报告、临床实验室检查、生命体征测量、心电图（ECG）参数和血清睾酮浓度。在本中期报告中，纳入了完成≥12 周治疗的患者。
结果
总体而言，第 1 部分有 15 名男性和第 2 部分有 10 名男性入组。不良事件大多为轻度至中度，与各药物的已知安全性特征一致。未观察到与治疗转换（来自之前的 ADT 治疗）或时间相关的临床实验室检查、生命体征测量或心电图参数的趋势。平均睾酮浓度保持在去势水平以下。
结论
瑞戈非尼联合阿比特龙或阿帕鲁胺治疗具有良好的安全性和耐受性，与各药物的已知特征一致。从其他 ADT 转换为瑞戈非尼后，仍保持去势水平的睾酮浓度。
临床试验注册
ClinicalTrials.gov 标识符：NCT04666129。
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