抗血管生成药治疗非小细胞肺癌

草船借箭 · 发表于 2013-12-10 15:05:27

dd163 发表于 2013-7-18 21:30
我家用阿西近三个月，三个月中效果很好，胸水与心包液都不涨了，停药后换易15天无效，CEA，胸水大涨。我家 ...

楼主家阿西用了三个月，不多见啊

草船借箭 · 发表于 2013-12-10 15:11:51

我老妈本来就有高血压、冠心病，现在2992有效中，如果我想EGFR耐药后轮换VEGFR的阿西是不是风险比较大，回头要看看阿西的用药讨论看看是否有类似情况。

老马 · 发表于 2013-12-10 16:47:45

Phase 3 Extension Trial of the Long Term Safety of BIBF 1120 in Patients With Idiopathic Pulmonary Fibrosis
http://www.clinicaltrial.gov/ct2 ... IBF1120&rank=27

BIBF 1120 in Recurrent Glioblastoma Multiforme
http://www.ncbi.nlm.nih.gov/pubmed/23184145
Abstract
Nintedanib (BIBF 1120) is a small, orally available, triple angiokinase inhibitor in phase III development (various indications) that targets VEGFR 1-3, FGFR 1-3, and PDGFR-α/β. This open-label, uncontrolled, phase II study assessed the efficacy and safety of nintedanib in patients with recurrent glioblastoma multiforme (GBM) who had previously failed radiotherapy plus temozolomide as first-line therapy (STUPP), or the same regimen with subsequent bevacizumab-based therapy as second-line treatment (BEV). Patients with a performance status of 0-1, histologically proven GBM, and measurable disease (by RANO) were enrolled. Nintedanib was given orally at a dose of 200 mg twice daily (bid), with magnetic resonance imaging undertaken every 8 weeks. The primary endpoint was objective response rate. The study was stopped prematurely following a preplanned futility analysis after inclusion of 13 patients in the STUPP arm and 12 in the BEV arm. Best response was stable disease (SD) in three patients (12 %); all other patients progressed within the first four 28-day cycles. One patient in the BEV arm has had SD for 17+ months. Median progression-free survival was 1 month and median overall survival was 6 months. Nintedanib had an acceptable safety profile, with no CTCAE grade 3-4 adverse events. Common adverse events were CTCAE grade 1-2 fatigue, loss of appetite, diarrhea, and nausea. Single-agent nintedanib (200 mg bid) demonstrated limited, but clinically non-relevant antitumor activity in patients with recurrent GBM who had failed 1-2 prior lines of therapy.

老马 · 发表于 2013-12-10 17:04:08

本帖最后由老马于 2013-12-10 17:06 编辑

Nintedanib（BIBF1120）是口服的抗血管生成的小分子激酶抑制剂，作用于VEGFR1-3、PDGF、FGFR1-3、RET 和 Fit3等。Hanna 等报道随机对照多中心Ⅲ期 Lume-Lung2 试验结果，比较了 Nintedanib+ 培美曲塞与安慰剂 + 培美曲塞二线治疗非鳞 NSCLC 的疗效。共计划入组 1116 例，主要研究终点为PFS。根据预先设定的中期 PFS分析结果而提前结束患者入组。共入组患者 713 例，两组分别为 353 例和 360 例，PFS 分别为4.4个月和3.6个月（P=0.0435），OS 分别为 12.2 个月和 12.7 个月（P=0.7921），ORR 分别为 9.1% 和 8.3%。两组患者黏膜炎、出血、高血压、血栓栓塞疾病、穿孔和手足综合征发生率均无差别。研究者同时还报道 Lume-Lung1 试验结果，比较了 Nintedanib 联合多烯紫杉醇与安慰剂联合多烯紫杉醇二线治疗 NSCLC 的疗效。主要研究终点为PFS。共入组1314例，两组分别为 655 例和 659 例，PFS 分别为 3.4 个月和2. 7 个月（P=0.0019），OS 分别为 10.1个月和 9.1 个月（P=0.2720）。腺癌和鳞癌无显著差别。

老马 · 发表于 2013-12-10 17:08:04

LUME-Lung 1试验是一项随机、双盲的Ⅲ期临床试验，旨在比较尼达尼布联合多西他赛和安慰剂联合多西他赛应用于一线治疗后的局部晚期和转移性NSCLC患者的结果。研究显示，尼达尼布联合多西他赛可使NSCLC腺癌患者的总生存期相较安慰剂联合多西他赛治疗组延长2.3个月(分别为12.6个月和10.3个月)。
　　该试验的主要终点是接受二线治疗的NSCLC患者的PFS。尼达尼布与多西他赛联合治疗组的PFS为3.4个月，相较于安慰剂组的2.7个月，在统计学上有显著性延长。
　　“LUME-Lung 1试验结果令人兴奋，因为初始化失败后，近十年以来，我们尚未看到接受二线治疗的NSCLC患者在总生存期方面出现任何进展。此外，这也是我们首次观察到，抗血管生长治疗能为那些初始化疗失败的NSCLC患者提供切实的受益。”LUME-Lung 1试验的主要研究者、德国Grosshansdorf肺科诊所胸外肿瘤科主任Martin Reck博士说。
　　LUME-Lung 1试验中最常见的不良事件是胃肠道反应和肝酶增高，而通过支持治疗或减少给药剂量能加以控制。
　　据悉，LUME-Lung 1试验在中国是由上海胸科医院廖美琳教授牵头，21家肿瘤中心参与，共入组患者173例。