• 主题
高级搜索  >
历史搜索 清空历史
首页> 美国卫生研究院文献>Neuro-Oncology >AT-06A PHASE II TRIAL OF TAMOXIFEN AND BORTEZOMIB IN PATIENTS WITH RECURRENT HIGH GRADE GLIOMA
【2h】

AT-06A PHASE II TRIAL OF TAMOXIFEN AND BORTEZOMIB IN PATIENTS WITH RECURRENT HIGH GRADE GLIOMA

机译：复发性高度胶质瘤患者中他莫昔芬和波妥昔单抗的AT-06A期II期试验

代理获取
本网站仅为用户提供外文OA文献查询和代理获取服务，本网站没有原文。下单后我们将采用程序或人工为您竭诚获取高质量的原文，但由于OA文献来源多样且变更频繁，仍可能出现获取不到、文献不完整或与标题不符等情况，如果获取不到我们将提供退款服务。请知悉。
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

BACKGROUND: Preclinical studies indicated that inhibition of NF-kB with bortezemib markedly enhance tamoxifen-mediated glioma apoptosis. A potentially synergistic cytotoxic effect of the combination may benefit patients with malignant gliomas. METHODS: We conducted single institution phase II trial to evaluate efficacy and safety of high dose tamoxifen with bortezomib in adults with recurrent high-grade glioma (HGG). Primary endpoint was radiographic response. Exclusion criteria included concurrent enzyme inducing anticonvulsants and grade ≥2 peripheral neuropathy. Patients received tamoxifen (120 mg PO twice daily) and bortezomib (1.3 mg /m2 of IV on days 3, 6, 10, 13, 24, 27, 31, and 34) of every 6 week cycle. Contrast-enhanced MRI was obtained at the end of each cycle. RESULTS: 42 patients are included in this analysis; 12 anaplastic glioma (AG), 30 glioblastoma (GBM), 32 males, and 10 females. Median age was 39 years (range 28-65) for AG, and 48 years (range 19-68) for GBM. Median KPS at entry was 90 for AG (range 70-100) and 80 for GBM (range 60-100). Median number of prior therapies were 3 (range 1-7). Grade ≥3 treatment related toxicities included lymphopenia (4 pts), hypophosphatemia (3 pts), thromobocytopenia (2 pts), and one instance each of hyponatremia, headache, dyspnea, and DVT. One GBM patient withdrew, two were removed for toxicity, and all others had progression. Among 40 patients evaluable for response, only one achieved stable disease unsustained beyond the first response assessment; all others had rapid progression. Median progression free survival was 5.9 and 5.7 weeks while median overall survival was 25.6 and 14.7 weeks for AG and GBM respectively. The study was closed early due to poor enrollment and therapeutic futility. CONCLUSION: Combination tamoxifen and bortezomib has no activity in this cohort of recurrent HGG. Poor results were likely influenced by poor penetration of bortezomib across blood brain barrier.
机译：背景：临床前研究表明，硼替佐米抑制NF-kB明显增强了他莫昔芬介导的神经胶质瘤的凋亡。该组合的潜在协同细胞毒性作用可能使恶性神经胶质瘤患者受益。方法：我们进行了单机构II期试验，以评估高剂量他莫昔芬联合硼替佐米在复发性高级别胶质瘤（HGG）成人中的疗效和安全性。主要终点是影像学反应。排除标准包括并发酶诱导抗惊厥药和≥2级周围神经病。患者每6周周期接受他莫昔芬（每天两次，每次120 mg PO）和硼替佐米（第3、6、10、13、24、27、31和34天的IV静脉注射1.3 mg / m2）。在每个周期结束时获得对比增强的MRI。结果：42例患者被纳入分析。 12例间变性神经胶质瘤（AG），30例胶质母细胞瘤（GBM），32例男性和10例女性。 AG的中位年龄为39岁（范围28-65），GBM的中位年龄为48岁（范围19-68）。进入时的KPS中位数对于AG为90（范围70-100），对于GBM为80（范围60-100）。先前治疗的中位数为3（范围1-7）。 ≥3级与治疗相关的毒性反应包括淋巴细胞减少症（4分），低磷血症（3分），血小板减少症（2分），以及低钠血症，头痛，呼吸困难和DVT中的一种。一名GBM病人退出，两名因毒性撤出，其他所有病人都有进展。在40例可评估反应的患者中，只有一个患者达到了稳定的疾病，只有在首次反应评估后才得以维持。所有其他人进展迅速。 AG和GBM的中位无进展生存期分别为5.9和5.7周，中位总生存期分别为25.6和14.7周。由于入选不良和治疗无效，该研究提早结束。结论：他莫昔芬和硼替佐米联合治疗在这一复发性HGG患者中无活性。硼替佐米穿过血脑屏障的渗透性差可能会影响结果的准确性。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
代理获取

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号