A phase II study of 2-methoxyestradiol (2ME2) NanoCrystalA® dispersion (NCD) in patients with taxane-refractory, metastatic castrate-resistant prostate cancer (CRPC)
A phase II study of 2-methoxyestradiol (2ME2) NanoCrystalA® dispersion (NCD) in patients with taxane-refractory, metastatic castrate-resistant prostate cancer (CRPC)
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DOI：
10.1007/s10637-010-9455-x
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发表时间：
2011-12-01
影响因子：
3.4
通讯作者：
Liu, Glenn
中科院分区：
文献类型：
--
作者：
Harrison, Michael R.;Hahn, Noah M.;Liu, Glenn
目的：2ME2 （PanzemA (R)）是雌二醇的非雌激素衍生物，具有抗增殖和抗血管生成活性。临床前数据支持前列腺癌的抗肿瘤活性。该试验评估了2ME2 NCD在紫杉烷难治性转移性CRPC患者中的疗效。实验设计：转移性CRPC患者，既往仅接受过一种紫杉烷为基础的治疗方案。所有患者均接受2ME2 NCD治疗，剂量为1500mg，每日口服4次，每28天重复一次。主要终点是第6个月的无进展生存期，次要终点是PSA反应。一个探索性终点是FDG-PET成像的代谢反应。结果：共计划50例。研究在21分后终止，因为无效分析显示主要终点不太可能达到。研究中位数周期数为2（范围< 1至12）。与研究药物相关的a级不良事件（AE）发生在7例（33%）患者中：肝功能检查升高、疲劳或虚弱、胃肠道出血和低钠血症。11例患者获得配对FDG-PET扫描。未观察到代谢反应。结论：在本研究中，2ME2 NCD似乎没有显著的临床活性。2ME2非传染性疾病耐受性良好，并显示出一定的生物活性。考虑到紫杉烷耐药人群的侵袭性生物学，细胞抑制剂如2ME2的潜在益处可能更好地在化疗前（或仅PSA升高）CRPC阶段实现。
Purpose: 2ME2 (PanzemA (R)) is a non-estrogenic derivative of estradiol with antiproliferative and antiangiogenic activity. Preclinical data support antitumor activity in prostate cancer. This trial evaluated the efficacy of 2ME2 NCD in patients with taxane-refractory, metastatic CRPC. Experimental Design: Patients with metastatic CRPC who had progressed on only one prior taxane-based regimen were eligible. All patients received 2ME2 NCD at 1,500 mg orally four times daily, repeated in 28 day cycles. The primary endpoint was progression-free survival at month 6, with a secondary endpoint of PSA response. An exploratory endpoint was metabolic response on FDG-PET imaging. Results: A total of 50 pts was planned. The study was terminated after 21 pts when a futility analysis showed the primary endpoint was unlikely to be reached. The median number of cycles on study was 2 (range < 1 to 12). Adverse events (AE) of grade a parts per thousand yen3 related to the study drug occurred in 7 unique patients (33%): elevations in liver function tests, fatigue or weakness, gastrointestinal hemorrhage, and hyponatremia. Paired FDG-PET scans were obtained for 11 pts. No metabolic responses were observed. Conclusions: 2ME2 NCD did not appear to have clinically significant activity in this study. 2ME2 NCD was well-tolerated and showed some evidence of biologic activity. Given the aggressive biology in this taxane-refractory population, the potential benefit from a cytostatic agent like 2ME2 might better be realized in the pre-chemotherapy (or rising PSA only) stage of CRPC.