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肺癌脑转新药ANG1005(GRN1005 )

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6881 13 老马 发表于 2012-12-6 22:27:07 |

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本帖最后由 老马 于 2012-12-6 22:32 编辑

ANG1005: Results of a phase I study in patients with advanced solid tumors and brain metastases.
Background: ANG1005 is a novel taxane derivative created from Angiochem's Engineered Peptide Compound (EPiC) platform shown to penetrate the blood-brain barrier (BBB) and tumor cells by targeting the low-density lipoprotein receptor-related protein (LRP), which is highly expressed on the surface of the BBB and upregulated on various tumor cells. Methods: Patients (pts) with advanced solid tumors, adequate organ function, ECOG ≤2 received ANG1005 by IV infusion q21d without premedication. Brain metastases were required at the maximum tolerated dose (MTD). Doses were escalated using a modified Fibonacci scheme in sequential cohorts of 1-6 pts each. Study objectives included characterizing safety, tolerability, PK, identifying the MTD and obtaining preliminary evidence of efficacy. Results: 56 pts received ANG1005 at doses of 30-700 mg/m2; 20 at 650 mg/m2, the identified MTD and recommended phase II dose. Median age: 54, male: 43%, ≥3 prior therapies: 73%, brain mets: 48 pts. Most common adverse events (≥Gr. 2, CTCAE v.3.0) were leucopenia (73%), neutropenia (66%), anemia (48%), and fatigue (30%); events were transient and manageable. The dose-limiting toxicity was Gr. 4 thrombocytopenia. No evidence of CNS toxicity or antibody production even in pts who received multiple doses. Only 5 infusion-related reactions and no significant peripheral neuropathy (1 Gr.3 at MTD). PK data indicate linear ANG1005 bioavailability and no accumulation. At 650 mg/m2, Cycle 1: Cmax 306 ug/mL, AUCinf 2571 ug·h/mL, T1/2 4.0 h, CL 285 mL/m2·h. Plasma concentrations of free paclitaxel measured at MTD revealed that it accounted for only a small fraction (~10%) of total plasma exposure. Overall disease control (≥ SD by RECIST) was achieved in 71% of pts dosed >300 mg/m2 including 7 pts who failed prior taxane therapy. PR in 7 pts at MTD: 3 Breast, 2 NSCL, 1 Ovarian, 1 SCL. Important reductions were also achieved in metastases located in organs including the liver, lung and lymph nodes. Median time to progression was 18 wks in responders (≥ SD) and 9.7 wks in all patients. Conclusions: ANG1005 is safe and well tolerated and demonstrates activity in advanced solid tumors and brain metastases, a disease for which there is currently no approved chemotherapy drug.
http://www.asco.org/ASCOv2/Meeti ... mp;abstractID=40334

http://www.clinicaltrials.gov/ct ... =GRN1005&rank=2
http://cancergrace.org/forums/index.php?topic=11353.0
http://www.clinicaltrials.gov/ct ... =GRN1005&rank=3
www.ncbi.nlm.nih.gov/pubmed/22203732
个人公众号:treeofhope

13条精彩回复,最后回复于 2014-6-19 11:21

一步错步步错  大学二年级 发表于 2012-12-7 15:56:17 | 显示全部楼层 来自: 四川资阳
谁能帮忙给翻译下呢
seacat  版主 发表于 2012-12-8 10:46:03 | 显示全部楼层 来自: 广东广州
真想一觉醒来,我在小学教室对着小学同桌说:“我做了好长一个梦。”
一步错步步错  大学二年级 发表于 2012-12-10 11:25:07 | 显示全部楼层 来自: 四川资阳
谢谢,只是一期也太遥远了.
成功  初中一年级 发表于 2012-12-10 14:17:37 | 显示全部楼层 来自: 河北唐山
晕,看不懂,不过有新药就是好事!
luohui  高中二年级 发表于 2012-12-11 06:53:00 | 显示全部楼层 来自: 美国
老马,谢谢你,能加你qq吗? 我爸多出脑转,现在吃特中,我特别关心脑转方面的用药,我也很想知道对于一些实验用药如果买到非正版,能否加你qq呢
cdlxyj2008  初中二年级 发表于 2012-12-12 15:15:42 | 显示全部楼层 来自: 河北唐山
希望早点面世
dgarden  初中二年级 发表于 2012-12-16 22:51:17 | 显示全部楼层 来自: 内蒙古包头
支持老马
黑月追风  初中一年级 发表于 2012-12-20 00:15:09 | 显示全部楼层 来自: 河南
在线翻译的
ANG 1005:结果第一阶段的研究治疗晚期实体瘤和脑转移瘤。背景:ANG 1005是一种新的紫杉烷衍生物创建angiochem的工程多肽化合物(史诗)平台证明穿透血脑屏障(血脑屏障)和肿瘤细胞靶向的低密度脂蛋白受体相关蛋白(蛋白),这是高度表达表面的血脑屏障和上调对不同肿瘤细胞。方法:患者(分)与先进的固体肿瘤,足够的器官功能,脑电图≤2收到ANG 1005的静脉注射,q21d无术前用药。脑转移所需的最大耐受剂量(最大耐受量)。剂量升级使用改进的Fibon acci方案在连续同伙每个1 - 6分。研究目标包括表征安全性,耐受性,峰,确定最大耐受量和获得初步证据的效力。结果:56例接受ANG 1005剂量30-700毫克/平方米;20在650毫克/平方米,确定最大耐受量和第二阶段的建议剂量。平均年龄:54,男:43%,73%,3≥事先疗法:大脑大都会队:48分。最常见的不良事件(≥组2,评价标准V3.0)为白细胞减少(73%),(66%)中性粒细胞减少,贫血(48%),和疲劳(30%);事件是短暂和管理。剂量限制性毒性组4的血小板减少症。没有证据的中枢神经系统毒性或抗体生产即使在警校谁收到多个剂量。只有5个输液反应和无显着周围神经病变(1 gr.3在最大耐受量)。峰数据表明线性ANG 1005生物利用度并没有积累。在650毫克/平方米,周期1:分别为306微克/毫升,aucinf 2571微克·小时\ /毫升,t 1 / 2 4小时,285毫升\ /平方米·小时血浆浓度无紫杉醇测定最大耐受量显示,它只占一小部分(~总数的10%)血浆暴露。综合疾病控制(≥处由上)取得了71%分剂量> 300毫克/平方米,包括7例谁没有事先紫杉醇治疗。公关在7分在最大耐受量:3,2是1,1个卵巢,中。重要的减少也取得了在转移位于器官包括肝,肺和淋巴结。位数进展时间为18周的反应(≥标准差)和9.7周所有患者。结论:ANG 1005是安全和耐受性良好,并演示活动先进的固体肿瘤和脑转移瘤,疾病,目前还没有批准的化疗
weiyi1900897111  初中三年级 发表于 2013-1-10 20:38:41 | 显示全部楼层 来自: 江西九江
新的紫杉烷衍生物 是新紫杉醇化疗药物吧?

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