Activity of 2 methoxyestradiol (Panzem® NCD) in advanced, platinum-resistant ovarian cancer and primary peritoneal carcinomatosis: A Hoosier Oncology Group trial
Activity of 2 methoxyestradiol (Panzem® NCD) in advanced, platinum-resistant ovarian cancer and primary peritoneal carcinomatosis: A Hoosier Oncology Group trial
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DOI：
10.1016/j.ygyno.2009.05.042
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发表时间：
2009-10-01
影响因子：
4.7
通讯作者：
Sidor, Carolyn
中科院分区：
文献类型：
--
作者：
Matei, Daniela;Schilder, Jeanne;Sidor, Carolyn
背景：2-甲氧基yestradiol （Panzem (R), 2ME2）是雌二醇的内源性代谢物，具有破坏微管稳定性和抗血管生成特性。本研究旨在确定2ME2作为纳米晶体(R)分散体（NCD）制剂用于复发性铂耐药上皮性卵巢癌（EOC）患者的活性和安全性。符合条件的患者为复发、铂耐药或难治性EOC，伴有可测量或可检测的疾病。先前治疗方案的数量没有限制。2ME2 NCD 1000mg口服，每日4次（q.i.d），连续用药4周。主要终点为客观缓解率（ORR）。次要终点是毒性评估、临床获益率（定义为经历客观反应、CA125反应或病情稳定（SD）的患者数量）、CA-125的平均变化、无离子生存（PFS）进展以及2me2的药代动力学分析。18名患者入组。中位年龄为65.5岁（范围40-73岁）。患者之前接受过5次治疗。最常见的不良事件是疲劳（78%）、恶心（78%）、腹泻（39%）、神经病变（50%）、水肿（39%）和呼吸困难（44%），大多数为1-2级。没有客观反应，但有7例患者的最佳反应是SO。其中，两名患者的SO持续时间超过12个月。临床获益率为31.3%。在预测的治疗窗口内观察到相当稳定的血浆2ME2水平。NCO制剂的2ME2在大量预处理的EOC患者中耐受性良好。这些经过大量预处理的患者中很少有病情持续稳定的。Elsevier Inc.出版。
Background. 2-Methoxyestradiol (Panzem (R), 2ME2) is an endogenous metabolite of estradiol that destabilizes microtubules and exerts anti-angiogenic properties. This study was conducted to determine the activity and safety of 2ME2 administered as a NanoCrystal (R) dispersion (NCD) formulation in patients with recurrent, platinum-resistant epithelial ovarian cancer (EOC).Methods. Eligible patients had relapsed, platinum-resistant or refractory EOC with measurable or detectable disease. There was no limit on the number of prior treatment regimens. 2ME2 NCD 1000 mg orally four times daily (q.i.d.) was administered continuously during 4 week cycles. The primary endpoint was objective response rate (ORR). Secondary endpoints were assessment of toxicity, rate of clinical benefit defined as the number of patients experiencing an objective response, a CA125 response or stable disease (SD) >3 months, mean change in CA-125, progress ion-free survival (PFS), and pharmacokinetic analyses of 2ME2.Results. Eighteen patients were enrolled. Median age was 65.5 (range 40-73). Patients had received a median of five prior treatments. The most common adverse events were fatigue (78%), nausea (78%), diarrhea (39%), neuropathy (50%), edema (39%), and dyspnea (44%), the majority being grade 1-2. There were no objective responses, but seven patients had SO as best response. Of those, two patients had SO for greater than 12 months. The rate of clinical benefit was 31.3%. Fairly stable plasma levels of 2ME2 ranging within the predicted therapeutic window were observed.Conclusions. The NCO formulation of 2ME2 is well tolerated in patients with heavily pretreated EOC. Few of these heavily pretreated patients had sustained stable disease. Published by Elsevier Inc.