本帖最后由 荷花池荒岛 于 2015-11-2 08:49 编辑
Nintedanib(BIBF1120,尼达尼布)
在美国nintedanib(商标名:OFEV)用于特发性肺纤维化的治疗。2014年11月28日,欧盟委员会(EC)批准nintedanib联合多西紫杉醇(docetaxel)用于一线化疗后腺癌肿瘤学为局部晚期或转移性复发性非小细胞肺癌(NSCLC)患者的治疗,商标名为Vargatef。
Nintedanib在欧盟获得批准主要基于LUME-Lung 1研究所获得的阳性结果,此项研究在27个国家纳入超过1300名患者。LUME-Lung 1试验是一项随机、双盲、III期临床试验,此项试验针对尼达尼布*联合多西他赛应用于一线治疗后的局部晚期/转移性NSCLC患者的效果与安慰剂联合多西他赛进行了比较1。此项试验纳入了来自欧洲、亚洲和南非的1,314 名患者,这些患者随机接受尼达尼布* 200 mg每日给药两次联合多西他赛 75mg/m2 每日给药一次的治疗方案(n=655)或安慰剂联合多西他赛的治疗方案(n=659),治疗时间为3周。
尼达尼布已被证实具有可控的不良事件谱,而且不会进一步损害患者的总体健康相关性生活质量。尼达尼布*联合多西他赛相较于多西他赛单药治疗不会显著增加停药率。
尼达尼布是一种每日口服一次的治疗药物,也是勃林格殷格翰公司抗肿瘤产品线中第二个获得注册批准的化合物。GIOTRIF® (阿法替尼‡)是抗肿瘤产品线中首个获准的药物,用于治疗特定类型的EGFR突变阳性的非小细胞肺癌患者。
尼达尼布是一种口服三联血管激酶抑制剂,可同时阻断3种生长因子受体:血管内皮生长因子受体(VEGFR 1-3)、血小板源性生长因子受体(PDGFR α和β)、成纤维细胞生长因子受体(FGFR 1-3)。所有这3种受体在血管生成和肿瘤生长过程中均发挥着重要作用。这些受体的阻断,可能导致血管生成的抑制,而血管生成在肿瘤生长中起着关键作用。
http://www.229877.com/article/2015/0113/article_35091.html
http://www.referencepreparation. ... /article_35155.html
备注一:临床剂量和剂型
1120在半衰期约为10小时,临床中测定的最大耐受剂量为200mg*2每天,推荐临床剂量剂量为150mg*2每天
使用胃溶胶囊封装,辅料和1120的混合比例为2:1,乳糖和淀粉均可。
参考:http://www.yuaigongwu.com/forum.php?mod=viewthread&tid=14804
备注二:憨豆精神拟定非小细胞肺癌(不含ALK阳性)轮换使用靶向药的方法及解读
http://blog.sina.com.cn/u/5306366644
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譬如易或特无效,可能有T790或CMET阻隔,那么就需要4002+易或特;或者直接用9291;或者用280+易或特,用这些添加和替换的一种解决;又譬如有人走第二步用2992无效,那么在下一循环再走到第二步时,就可以用299804或26B代替2992;又譬如已经证实了第三步凡德他尼非常无效(CEA升2至几倍),在走到该凡德上场的时候改用半量易或特+半量阿西替尼(一起下肚),这两药联合就可能顶上凡德的作用;又譬如该吃阿西替尼而已知阿西替尼必定无效,这时可用其他抗血管生成抑制剂,如1120、多吉美、索坦、7080等等,也可以半量280+阿西替尼(假如已经检测存在CMET扩增的话)。
四步法的用药是开放的,它重视的是每一步需要打击抑制的靶点,只要达到这些目的,每一步的用药都可以在既定的目的下因着靶点而添加或替换。
这样的添加和替换,如何保证其正确性?即如何保证用药能击中靶点?这就需要精确的全面的基因检测,哪种基因有突变,哪种基因有扩增,哪种基因有高表达,都尽可能在用药前一目了然。否则,有可能添加错,有可能该添加的没添加,有可能该替换的没替换。
举阿西替尼无效为例。如果存在CMET扩增,那么,CMET与肝细胞生长因子结合,就可以使阿西替尼无效,但这时采用280+阿西替尼,很可能就顺利解决这个遗憾;如果VEGFR很弱,不如成纤维生长因子强大,或不如血小板样生长因子强大,那么,这时用1120代替阿西替尼,可能这一步就走得非常美好;又或者存在PI3K扩增,这时用120+阿西替尼就可能很好;又譬如存在缺氧因子,这时添加一些依维莫司则会收到奇效……诸如此类的添加和替换是个大舞台,有待有心之人大胆之人有准备有凭据地尝试实践,他们关于肿瘤基因靶点和关于靶向药的靶点的知识是必不可少的。
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备注三:
A double blind phase II study of BIBF 1,120 in patients suffering from relapsed advanced non-small cell lung cancer
http://meeting.ascopubs.org/cgi/content/short/25/18_suppl/7635
2007 American Society of Clinical Oncology
Background: Vascular endothelial-(VEGF), platelet derived- (PDGF), and fibroblast growth factor (FGF) with their receptors compose critical cellular pathways controlling angiogenesis. BIBF 1120 is an oral potent triple angiokinase inhibitor targeting VEGFR, PDGFR, FGFR kinases. Methods: In this double blind multi-center trial, patients with an ECOG score of 0–2 with locally advanced or metastatic (stage IIIB/IV) relapsed NSCLC after failure of first or second line chemotherapy were randomly assigned to daily treatment with 2x250 mg or 2x150 mg of BIBF 1,120 until progression. In the event of dose limiting toxicity, a single dose reduction to open label treatment with 2x150 or 2x100 mg of BIBF 1,120 was allowed. Patients with stable brain metastases or squamous cell carcinoma were not excluded. Primary endpoints were progression free survival (PFS) and objective tumor response (RECIST, determined every 6 weeks). Results: Seventy three of 74 patients enrolled received BIBF 1120 (61% males, median age: 64 years, range 36–80). The most common histology was adenocarcinoma (55%), followed by squamous cell carcinoma (23%). The median PFS of all patients (n= 73) was 1.6 months without significant difference between both treatment arms. The stable disease rate was 48% without objective tumour responses. However, patients with an ECOG performance status of 0 or 1 (n= 57) had a median PFS of 2.9 months and a three- and 5 months PFS rate of 46% and 31%, without any difference between both treatment arms. The stable disease rate was 59%. Patients treated with 2x250 mg per day had more dose limiting CTCAE Grade 3 and 4 toxicities compared with patients treated with 2x150 mg (27% versus 2.8%, p=0.006, two-sided Fisher-test). The most frequent adverse events irrespective of relatedness observed in 73 patients were of CTCAE Grade 1 or 2 and included nausea (41%), diarrhoea (41%), vomiting (33%), fatigue (29%) and abdominal pain (22%). Grade 3 and 4 toxicities included nausea (8%), diarrhoea (7%), vomiting (4%), abdominal pain (4%) and AST and/or ALT elevations (5.4%). Conclusions: BIBF 1120 is safe and well tolerated and showed promising efficacy data in ECOG 0–1 patients. A high disease control rate of 59% could be observed.
*Common Terminology Criteria for Adverse Events(CTCAE)
*ECOG performance status:http://ecog-acrin.org/resources/ecog-performance-status
备注四:论坛网友服药经验
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