非小细胞肺癌脑转治疗方法荟萃（更新于2011年11月9日）

5. A phase II study of daily afatinib (BIBW 2992) with or without temozolomide (21/28 days) in the treatment of patients with recurrent glioblastoma.
Meeting:
2011 ASCO Annual Meeting
Abstract No:
2010
Citation:
J Clin Oncol 29: 2011 (suppl; abstr 2010)


Author(s): D. D. Eisenstat, L. B. Nabors, W. P. Mason, J. R. Perry, W. R. Shapiro, P. Kavan, S. Phuphanich, Y. Fu, X. J. Cong, M. Shahidi, D. A. Reardon; CancerCare Manitoba, University of Manitoba, Winnipeg, MB, Canada; University of Alabama at Birmingham, Birmingham, AL; Princess Margaret Hospital, University of Toronto, Toronto, ON, Canada; Sunnybrook Health Sciences Centre, Toronto, ON, Canada; St. Joseph's Hospital and Medical Center, Phoenix, AZ; McGill University and Segal Cancer Centre, Jewish General Hospital, Montreal, QC, Canada; Cedars-Sinai Medical Center, Los Angeles, CA; Boehringer Ingelheim, Ridgefield, CT; Boehringer Ingelheim, Bracknell, United Kingdom; Duke University Medical Center, Durham, NC

Abstract Disclosures

Abstract:
Background: Epidermal growth factor receptor (EGFR) is over-expressed in ~50% of glioblastoma (GBM); approximately half express the constitutively active mutant receptor EGFRvIII. Afatinib (A), an irreversible erbB family blocker (including EGFRvIII), has high levels of in vitro activity in tumor cell lines resistant to reversible EGFR inhibitors.Temozolomide (T) can overcome O6-methylguanine methyltransferase (MGMT) resistance. We hypothesized that daily A or daily A+T (AT, 21/28 days) may be an effective treatment for recurrent GBM. Methods: The trial’s primary objectives were to evaluate efficacy and safety of A and AT compared to T in recurrent GBM, and to assess molecular determinants of response to A. Patients (pts) with histologically-confirmed GBM at first recurrence after prior combined chemoradiotherapy were randomized 1:1:1 to receive A, AT or T. Randomization was stratified by age (≤50 vs. >50 years) and Karnofsky Performance Status (KPS; 70, 80 vs. 90, 100). A was dosed daily at 40 mg; T was dosed at 75 mg/m2 for 21/28 days. The primary endpoint was 6-month progression-free survival rate (PFS-6). Independent imaging and pharmacokinetic assessments were obtained. Archival tumor samples were assessed for EGFR, EGFRvIII, PTEN, pAKT and MGMT. Patients were treated until undue toxicity or disease progression. Results: Enrolment was completed in June 2010. 119 pts were randomized (median age 58 years [range 22–81]) and 54% had a KPS of 70–80. The most frequent AEs in pts A-treated pts were diarrhea (70% and 68% in A and AT, respectively) and rash (80% and 69%). PFS-6 by investigator assessment was 3%, 17% and 22% in the A, AT and T arms, respectively. A was statistically worse compared to T (p=0.008); AT was comparable to T (p =0.59). Best overall response included partial response in one, five and six pts and SD in 22, 20 and 21 pts in A, AT and T, respectively. Preliminary biomarker data in 54 pts suggested durable disease control in EGFRvIII-positive pts treated with A/AT. Updated biomarker data will be presented. Conclusions: Afatinib has limited single-agent activity in recurrent GBM; however, potential activity in biomarker-selected pts warrants further evaluation.

一共有119名病人，按1：1：1分组，临床结果表明，2992单药组的有效率缓解人数是1人，联合组是5人，替莫措胺组是6人；，2992单药组的稳定人数是22人，联合组是20人，替莫措胺组是21人。
说明2992单药对胶质瘤的效率还成，但比替莫措胺差不少，而2992联合替与替单药没有区别。

感谢楼主，我母亲刚开始放疗，这个对我太有用了。。。

我爸爸也马上要结束20次的头部放疗了，副作用太大了，大小便困难，四肢无力，呕吐没食欲，希望停止放疗后能够慢慢改善吧。

Dr. Loiselle has explained that there are some subtle nuances: http://cancergrace.org/forums/index.php?topic=6708.150

Specifcially, Dr. West has said, "My understanding is that Cyber knife and Gamma Knife have very subtle differences but are essentially brand names for different company models of very comparable machines, like two different camera company's names for image stabilizing technology that works remarkably similarly.

Dr. Loiselle has said, "With regard to your question about Cyberknife vs. Gamma Knife - Dr. West is right - both machines typically offer highly effective and comparable treatment in this situation.  There are a few differences in the technology which make one or the other more useful in certain situations, but in your case, they likely will have a similar effect.

First off, there is no knife with either device - though they do provide very precise, highly focused radiotherapy.  They both are very good at targeting small brain lesions.  Overall, both devices can crossfire pencil thin radiation beams at small brain lesions, effectively depositing high dose radiation in the target tumor, while at the same time dramatically limiting the otherwise healthy brain tissue to a safe low dose.  For both cyberknife and gamma knife, each radiation beam generated is quite weak, but where they all cross, a high dose of radiation is delivered... your physicians will align that beam crossing point right on the tumor.

For Gamma knife treatment, a metal headframe is affixed to the skull with typically 4 pins which go through the skin in to the outer table of the skull.  The skin is numbed with lidocaine, so the pin placement is actual typically quite bearable.

For Cyberknife treatment, a custom made plastic mask is used to hold the head still, and the cyberknife has cameras which track and monitor the position of the skull within the mask.  No pins, no needles.

Because the Gamma Knife frame is fixed to the skull, it is probably 1 mm or so more precise.  However, in your circumstance, that may not be relevant or meaningful in terms of risk for side effects nor effectiveness in controlling the cancer.  In some cases, that extra 1mm makes a really big difference - for example, when treating to higher doses than likely to be necessary for your situation or for irradiating targets right next to the nerves which control things like vision.   Sometimes though, if you have one truly very small lesion, gamma knife may be slightly better in its ability to really focus a very small target radiation dose to one very small area.  Gamma knife can also sometimes be better if one decides to treat multiple brain lesions with stereoctactic radiosurgery.

Both the Gamma Knife and Cyberknife share the ability to treat tumors inside the brain.  The Cyberknife has the additional cabability to treat tumors in the lung, spine, and liver.

The Gamma knife has the advantage for intracranial targets that it often is a much faster treatment (with new/updated GAmma Knife machinery that is).   Sometimes the cyberknife treatments can take longer.  Also from a more technical perspective, the gamma knife radiation beam angles and cyberknife beam angles are different.  The Gamma knife beam array hemisphere is above the head.  The cyberknife beam array hemisphere is in front of the head.  These technical factors sometimes make one treatment better than the other for a certain situation.

I hope that helps.  Either way - both cyberknife and gamma knife are very good.  For most patients with brain metastases as you have described, either technology can offer precise, high focused, and safe treatment."

http://cancergrace.org/forums/index.php?topic=10185.0

http://cancergrace.org/radiation/2011/06/10/brain-mets-cases/

http://cancergrace.org/radiation ... f-brain-metastases/

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伽马刀和X刀治疗脑转移瘤的讨论
http://forum.e2002.com/forum.php?mod=viewthread&tid=150638

中医根据咳嗽的不同表征，将咳嗽分为5种类型。 风寒咳嗽：吐稀痰，伴有头痛、鼻塞、流清涕、怕冷及发烧；风热咳嗽：多有发热、口干、吐痰不爽、喉痛；燥火咳嗽：干咳、少痰、唇及咽喉干燥；痰湿咳嗽：痰 多粘稠，喉中呼噜作响，可能出现胸闷，呼吸急促等症状；阴虚咳嗽：咳嗽时发时止，面目苍白、两颧（眼睛之下的颜面骨）发红、提气不上或手足发烧，有时痰中 带血或咯血。

用白萝卜来食疗的主要是对风寒咳嗽而言；用藕汁、梨汁食疗的是对风热咳嗽；用新鲜熟木瓜是治疗痰热咳嗽；用桔皮是辅助治疗痰湿咳嗽；用百合是相对于肺气虚久咳或阴虚久咳而言。

老马 发表于 2012-5-9 22:59

                               
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5. A phase II study of daily afatinib (BIBW 2992) with or without temozolomide (21/28 days) in the t ...

     借用老马的贴子上再说下我妈妈脑转的治疗情况，希望对脑转病友能起到点参考作用。2012年2月15号复查脑部进展以后，两次阿瓦无效后换了2992，现在回头来看第一个月2992是有效的，几个大的病灶略有缩小，其他稳定，但是第二个月2992彻底失败，脑部所有病灶都增大了，而且出现了新发病灶。无奈之下改用阿帕，副作用巨大而且头晕越来越严重，10天以后只好重新回到原来有效的方案脉冲特+替莫，第二天头晕就有好转。看来我们脑转主要还是靠脉冲特+替莫，实在不行的时候用2992顶一下。现在最担心第二次脉冲特+替莫有效的时间可能不会长，后面还能有什么药可用。
     另外，正如憨叔以前提醒我的，脉冲特的心脏毒性太大，已经把四粒特改成了三粒，心脏还是不舒服，尤其是用药的第一天心脏副作用立竿见影，等到逐渐好转又到了第二次脉冲的时间，很难办。辅酶Q10、倍他乐克、潘南金都在用，都不见效。

85749326 发表于 2012-3-3 21:24

                               
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我在网上查看到 转移来的脑瘤是没有血脑屏障的 那正常来讲 是不是特罗凯能够起到控制肺鳞癌脑转移的瘤呢？求 ...

同问啊！还没人回答吗？