• 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>other >ACTR-14. PHASE I STUDY OF AZD1775 WITH RADIATION THERAPY (RT) AND TEMOZOLOMIDE (TMZ) IN PATIENTS WITH NEWLY DIAGNOSED GLIOBLASTOMA (GBM) AND EVALUATION OF INTRATUMORAL DRUG DISTRIBUTION (IDD) IN PATIENTS WITH RECURRENT GBM
【2h】

ACTR-14. PHASE I STUDY OF AZD1775 WITH RADIATION THERAPY (RT) AND TEMOZOLOMIDE (TMZ) IN PATIENTS WITH NEWLY DIAGNOSED GLIOBLASTOMA (GBM) AND EVALUATION OF INTRATUMORAL DRUG DISTRIBUTION (IDD) IN PATIENTS WITH RECURRENT GBM

机译：ACTR-14。新诊断的胶质母细胞瘤（GBM）患者接受放射治疗（RT）和替莫唑胺（TMZ）治疗的AZD1775的第一阶段研究以及复发性GBM患者的气管内药物分布（IDD）评价

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

AZD1775 is an oral small molecular inhibitor of the G2/M checkpoint regulator Wee1. The Adult Brain Tumor Consortium 1202 trial () is a phase I, open label, multicenter dose-finding study of AZD1775 in combination with standard RT and TMZ followed by an IDD study for patients undergoing surgery for recurrent GBM. Dose of AZD1775 was increased in a 3 + 3 design M-F during concurrent RT/TMZ and x 5d/28d cycle with adjuvant TMZ in separate cohorts. A combination cohort with both concurrent and adjuvant AZD1775 at MTD and analysis of PK/PD and IDD at MTD in patients undergoing surgery for recurrent GBM followed. MTD was 200 mg for concurrent with 2/6 patients experiencing DLTs (grade 4 neutropenia, grade 3 ALT elevation). MTD for the adjuvant cohort was 425 mg with 1/6 patients experiencing DLT (grade 4 decrease in ANC). 6/12 patients experienced DLTs when cohorts were combined, however, five during the concurrent phase. Three patients had grade ≥3 ALT/AST elevation, one had grade 3 afib, and one had grade 4 neutropenia/thrombocytopenia, grade 3 dehydration/fatigue/muscle weakness. A sixth patient had grade 4 neutropenia in the first adjuvant cycle. Following amendment, an additional 6 patients were enrolled with 150 mg (concurrent) and 425 mg (adjuvant) combination and are in the observation period with one DLT currently. Drug concentration in contrast enhancing and non-enhancing brain tumor was 4–8 x and 0.5–2.6 x greater than plasma, respectively for patients on IDD portion.CONCLUSIONSAZD1775 in combination with RT/TMZ at 200 mg qd M-F with concurrent RT/TMZ and 425 mg qd x 5d/28d cycle in combination with adjuvant TMZ had unacceptable DLT rate in the concurrent phase. A cohort with 150 mg concurrent/425 mg adjuvant has competed accrual with acceptable rates of toxicity currently in observation. AZD1775 has good penetration to non-enhancing and enhancing tumor areas.
机译：AZD1775是G2 / M检查点调节剂Wee1的口服小分子抑制剂。成人脑肿瘤联合会1202试验（）是AZD1775与标准RT和TMZ联合进行的I期，开放标签，多中心剂量寻找研究，随后是针对复发性GBM手术患者的IDD研究。在同时的RT / TMZ和x 5d / 28d周期中，在单独的队列中使用佐剂TMZ在3 + 3设计M-F中增加了AZD1775的剂量。在复发性GBM手术中，在MTD时同时使用和佐剂AZD1775联合队列，并在MTD时分析PK / PD和IDD。对于2/6患有DLT（4级中性粒细胞减少症，3级ALT升高）的患者，MTD为200毫克。辅助队列的MTD为425 mg，其中1/6例患者经历了DLT（ANC降低4级）。当队列合并时，有6/12例患者经历了DLT，但是在同期阶段有5例。 3例ALT / AST升高≥3级，1例3房颤，1例中性白细胞减少/血小板减少，3例脱水/疲劳/肌无力。第六例患者在第一个辅助周期中出现4级中性粒细胞减少。修改后，又有6名患者接受了150 mg（并行）和425 mg（佐剂）的合并治疗，并且处于观察期，目前有1个DLT。 IDD部分患者在对比增强和非增强脑瘤中的药物浓度分别比血浆高4–8倍和0.5–2.6 x。结论SAZD1775与200 mg qd MF的RT / TMZ联用并发RT / TMZ和425 mg qd x 5d / 28d周期与佐剂TMZ结合的同时期DLT率不可接受。具有150毫克并发/ 425毫克佐剂的队列已在目前的观察中以可接受的毒性发生竞争。 AZD1775对非增强和增强肿瘤区域具有良好的渗透性。

著录项

相似文献

  • 外文文献
  • 中文文献
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