Inoue Takahiro, Ogura Keiji, Kawakita Mutushi, Tsukino Hiromasa, Akamatsu Shusuke, Yamasaki Toshinari, Matsui Yoshiyuki, Segawa Takehiko, Sugino Yoshio, Kamoto Toshiyuki, Kamba Tomomi, Tanaka Shiro, Ogawa Osamu
Department of Urology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Department of Urology, Japanese Red Cross Otsu Hospital, Otsu, Japan.
Clin Genitourin Cancer. 2016 Feb;14(1):e9-e17. doi: 10.1016/j.clgc.2015.08.008. Epub 2015 Sep 2.
Despite the favorable toxicity profile at the standard dose of 560 mg daily, the tolerability and toxicology of estramustine phosphate (EMP) have been a cause for concern at administration. Moreover, we do not know whether a lower dose of 280 mg of EMP daily can be administered with some efficacy and fewer side effects. The results of our phase II study suggest that low-dose EMP is a safe treatment option with the same efficacy in patients with castration-resistant prostate cancer.
We evaluated the efficacy and safety of low-dose estramustine phosphate (EMP) in Japanese patients with castration-resistant prostate cancer (CRPC).
The present study was a single-arm, nonrandomized prospective study in which all patients received EMP orally twice daily for a total dose of 280 mg/day. A total of 31 patients with CRPC were enrolled from December 2009 to December 2012 at 5 institutions in Japan. The primary endpoint was the prostate-specific antigen (PSA) response, defined as a 50% decline in the serum PSA level, confirmed ≥ 3 weeks later. The secondary endpoints included the objective response rate, interval to PSA progression, PSA response duration, progression-free survival, disease-specific survival, overall survival, safety, and quality-of-life assessment using the Functional Assessment of Cancer Therapy-Prostate scores.
Ten patients (32%) had a PSA response, and no patient had an objective response. The treatment was well tolerated, and the most frequent toxicities were grade 1 to 2 nausea/vomiting, anorexia, and gynecomastia. The median interval to PSA progression was 140 days (95% confidence interval [CI], 117-260 days). The PSA response duration was 119 days (95% CI, 49-219 days). The median progression-free survival was 213 days (95% CI, 167-422 days). The 3-year disease-specific survival and overall survival rates were 68.6% (median not reached; 95% CI, 33 months to not available) and 59.9% (median 42 months, 95% CI, 28 months to not available), respectively.
Low-dose EMP seems to be a safe treatment option with some efficacy in patients with CRPC.
尽管每日560毫克的标准剂量具有良好的毒性特征，但磷酸雌莫司汀（EMP）的耐受性和毒理学在给药时一直令人担忧。此外，我们不知道每日280毫克的较低剂量EMP是否可以在具有一定疗效且副作用较少的情况下给药。我们的II期研究结果表明，低剂量EMP是去势抵抗性前列腺癌患者的一种安全治疗选择，且疗效相同。
我们评估了低剂量磷酸雌莫司汀（EMP）对日本去势抵抗性前列腺癌（CRPC）患者的疗效和安全性。
本研究是一项单臂、非随机前瞻性研究，所有患者每日口服EMP两次，总剂量为280毫克/天。2009年12月至2012年12月期间，日本5家机构共招募了31例CRPC患者。主要终点是前列腺特异性抗原（PSA）反应，定义为血清PSA水平下降50%，并在≥3周后得到确认。次要终点包括客观缓解率、PSA进展间隔、PSA反应持续时间、无进展生存期、疾病特异性生存期、总生存期、安全性以及使用癌症治疗功能评估-前列腺评分进行的生活质量评估。
10例患者（32%）出现PSA反应，无患者出现客观缓解。治疗耐受性良好，最常见的毒性反应为1至2级恶心/呕吐、厌食和男性乳房发育。PSA进展的中位间隔为140天（95%置信区间[CI]，117 - 260天）。PSA反应持续时间为119天（95%CI，49 - 219天）。中位无进展生存期为213天（95%CI，167 - 422天）。3年疾病特异性生存率和总生存率分别为68.6%（中位未达到；95%CI，33个月至不可用）和59.9%（中位42个月，95%CI，28个月至不可用）。
低剂量EMP似乎是CRPC患者的一种安全治疗选择，且具有一定疗效。
