醋酸阿比特龙在未经化疗的日本转移性去势抵抗性前列腺癌男性患者中的2期试验（JPN - 201研究）
A phase 2 trial of abiraterone acetate in Japanese men with metastatic castration-resistant prostate cancer and without prior chemotherapy (JPN-201 study).
作者信息
Matsubara Nobuaki, Uemura Hirotsugu, Satoh Takefumi, Suzuki Hiroyoshi, Nishiyama Tsutomu, Uemura Hiroji, Hashine Katsuyoshi, Imanaka Keiichiro, Ozono Seiichiro, Akaza Hideyuki
机构信息
Division of Oncology and Hematology, National Cancer Center Hospital East, Chiba
Department of Urology, Kinki University Faculty of Medicine, Osaka.
出版信息
Jpn J Clin Oncol. 2014 Dec;44(12):1216-26. doi: 10.1093/jjco/hyu149. Epub 2014 Oct 15.
OBJECTIVE
Abiraterone acetate has been approved in >70 countries for chemotherapy-naïve metastatic castration-resistant prostate cancer patients. Efficacy and safety of abiraterone acetate (1000 mg/once daily) with prednisolone (5 mg/twice daily) in chemotherapy-naïve Japanese patients with metastatic castration-resistant prostate cancer was evaluated.
METHODS
Men, ≥20 years, with prostate-specific antigen levels of ≥5 ng/ml and evidence of progression were enrolled in this Phase 2, multicenter, open-label study. Primary efficacy endpoint was proportion of patients achieving a prostate-specific antigen decline of ≥50% from baseline (prostate-specific antigen response) after 12 week of treatment. Secondary efficacy endpoints and safety were assessed.
RESULTS
A confirmed prostate-specific antigen response was observed in 29/48 (60.4%) patients by week 12; lower limit of two-sided 90% confidence interval was >35% (threshold response rate), demonstrating efficacy of abiraterone acetate. Secondary efficacy endpoints: prostate-specific antigen response rate during treatment period: 62.5%; objective radiographic response, partial response: 4/18 (22.2%) patients; complete response: none; stable disease: 11/18 (61.1%) patients; median percent change in prostate-specific antigen level from baseline at Week 12: -66.62%. Median prostate-specific antigen response duration and progression-free survival were not reached, and median radiographic progression-free survival was 253 days. Of 31/48 (64.6%) patients experienced adverse events of special interest; most common was hepatic function abnormality (37.5%, Grade 3: 10.4%). One Grade 3 hypertension was the only mineralocorticoid adverse event >Grade 1/2.
CONCLUSIONS
Efficacy of abiraterone acetate plus prednisolone was demonstrated by decline in prostate-specific antigen levels with evidence of antitumor activity by radiography in Japanese patients with chemotherapy-naïve metastatic castration-resistant prostate cancer. Abiraterone acetate plus prednisolone had an acceptable safety profile.
CLINICAL TRIAL REGISTRATION NO
NCT01756638.
目的
醋酸阿比特龙已在70多个国家获批用于未经化疗的转移性去势抵抗性前列腺癌患者。评估了醋酸阿比特龙（1000毫克/每日一次）联合泼尼松龙（5毫克/每日两次）用于未经化疗的日本转移性去势抵抗性前列腺癌患者的疗效和安全性。
方法
年龄≥20岁、前列腺特异性抗原水平≥5纳克/毫升且有疾病进展证据的男性纳入了这项2期、多中心、开放标签研究。主要疗效终点是治疗12周后前列腺特异性抗原水平较基线下降≥50%的患者比例（前列腺特异性抗原反应）。评估了次要疗效终点和安全性。
结果
到第12周时，29/48（60.4%）的患者出现了确认的前列腺特异性抗原反应；双侧90%置信区间下限>35%（阈值反应率），证明了醋酸阿比特龙的疗效。次要疗效终点：治疗期间前列腺特异性抗原反应率为62.5%；客观影像学反应，部分缓解：4/18（22.2%）的患者；完全缓解：无；疾病稳定：11/18（61.1%）的患者；第12周时前列腺特异性抗原水平较基线的中位变化百分比为-66.62%。未达到前列腺特异性抗原反应持续时间和无进展生存期的中位数，影像学无进展生存期的中位数为253天。31/48（64.6%）的患者发生了特别关注的不良事件；最常见的是肝功能异常（37.5%，3级：10.4%）。1例3级高血压是唯一大于1/2级的盐皮质激素不良事件。
结论
在未经化疗的日本转移性去势抵抗性前列腺癌患者中，醋酸阿比特龙联合泼尼松龙可使前列腺特异性抗原水平下降，影像学显示有抗肿瘤活性，证明了其疗效。醋酸阿比特龙联合泼尼松龙的安全性可接受。
临床试验注册号
NCT01756638。
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