卡博替尼XL184试药讨论（百度快照1-15页完整,LOLY提供）

ggyy · 发表于 2011-12-12 21:56:16

我妈妈前几天吃184腹泻，这两天又便秘的厉害，看了副作用：可能交替出现。原来如此。

独行 · 发表于 2011-12-15 19:29:28

我爸爸184副作用明显了，侥幸的心理失败了，恶心，心慌，乏力，没有食欲，我看手上也出现症状了，有水泡，大家告诉我怎么处理啊

慧质兰馨 · 发表于 2011-12-15 21:02:25

独行发表于 2011-12-15 19:29

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我爸爸184副作用明显了，侥幸的心理失败了，恶心，心慌，乏力，没有食欲，我看手上也出现症状了，有水泡，大 ...

恶心加服维生素B6；,心慌加服黄楊宁片和稳心颗粒；没食欲吃几天香砂养胃丸；手指的问题用百多邦。我家老歌吃184出现上述症状时的处置方法。对184的副作用有改善。

独行 · 发表于 2011-12-16 20:56:27

谢谢蕙质兰心！

64103474 · 发表于 2011-12-18 11:40:02

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太阳 · 发表于 2011-12-20 15:27:43

我妈妈12月17日开始服用184，每天100毫克，现在四天了，暂时还没有反映，希望骨转痛能减轻一些

老马 · 发表于 2011-12-20 15:35:00

J Clin Oncol 28:15s, 2010 (suppl; abstr 3017)
Author(s):
H. A. Wakelee, S. N. Gettinger, J. A. Engelman, P. A. Janne, H. J. West, D. S. Subramaniam, J. W. Leach, M. B. Wax, Y. Yaron, P. Lara Jr.; Stanford University School of Medicine, Stanford, CA; Yale University School of Medicine, New Haven, CT; Massachusetts General Hospital Cancer Center, Boston, MA; Dana-Farber Cancer Institute, Boston, MA; Swedish Cancer Institute, Seattle, WA; Georgetown University Hospital Lombardi Comprehensive Cancer Center, Washington, DC; Park Nicollet Institute, St. Louis Park, MN; Summit Medical Group, Summit, NJ; Exelixis, South San Francisco, CA; University of California, Davis, Sacramento, CA
Abstract:

Background: MET and VEGF play important roles in the pathobiology of NSCLC, and are associated with resistance to E. XL184 is an oral, potent inhibitor of MET, VEGFR2, and RET, with antitumor activity in combination with E in NSCLC xenografts with acquired E resistance. Thus, XL184 + E may be effective in pts with acquired E resistance. Methods: Adults with previously treated advanced NSCLC received daily doses of XL184 + E in a 3 + 3 design using combination doses across 5 cohorts in 2 parallel arms (A and B). Objectives include safety, pharmacokinetics (PK), pharmacodynamics, and maximum tolerated dose (MTD) determination. RECIST response is assessed every 8 weeks. Pts with at least 2 post-baseline tumor assessments or pts who discontinued early for PD or AE were assessable for response. Results: 54 NSCLC pts have been enrolled in phase Ib, the majority had prior E. The dose levels were: arm B (75 mg XL184 + 150 mg E and 50 mg XL184 + 150 mg E (MTD) and arm A (75 mg XL184 + 100 mg E; 125 mg XL184 + 100 mg E; and 125 mg XL184 + 50 mg E). MTD determination of arm A is ongoing. Across all dose levels, 12 pts experienced at least 1 DLT: diarrhea, elevated AST, palmar-plantar erythrodysesthesia, mucositis, hypertension, hypokalemia, elevated lipase, and fatigue. Of 34 pts in safety database, most frequent frade 3/4 AEs were diarrhea (26%), fatigue (15%), dyspnea (12%), and hypoxia (9%). Preliminary PK analysis does not show evidence of DDI. Genotyping plasma tumor DNA from 28 pts revealed EGFR T790M mutations in 7 pts (25%). FISH analysis of circulating tumor cells from 7 pts revealed MET copy number gain in 2 pts (28%). Six of 36 pts assessable for response including at least 3 pts with prior E therapy had ≥ 30% reduction in tumor measurements on at least 1 post-baseline scan, including 3 with a cPR (1 with MET amplification). Prolonged SD ≥ 4 months has been observed in some pts including one pt for 9+ months and one pt with EGFR T790M. Conclusions: The overall safety and tolerability profile of XL184 + E appears acceptable without evidence of a XL184/E DDI. Encouraging clinical activity of XL184 + E was observed in a largely E pretreated population, including pts with EGFR T790M and MET amplification.