非小细胞肺癌脑转治疗方法荟萃（更新于2011年11月9日）

Neuro Oncol. 2012 Oct 25. [Epub ahead of print]


A phase I/II trial of vandetanib for patients with recurrent malignant glioma.

Kreisl TN, McNeill KA, Sul J, Iwamoto FM, Shih J, Fine HA.
Source
Neuro-Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (T.K., K.M., F.I., J.S., H.F.); Biometric Research Branch, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, Maryland (J.S.).

Abstract
Vandetanib is a once-daily multitargeted tyrosine kinase inhibitor of vascular endothelial growth factor receptor-2, epidermal growth factor receptor, and the rearranged-during-transfection oncogene. A phase I trial was conducted to describe the pharmacokinetics of vandetanib in patients with recurrent glioma on enzyme-inducing anti-epileptic drugs (EIAEDs) and to identify the maximum tolerated dose (MTD) in this population. A phase II trial evaluated the efficacy of vandetanib in patients with recurrent malignant glioma not on EIAEDs as measured by 6-month progression-free survival (PFS6). In the phase I trial, 15 patients were treated with vandetanib at doses of 300, 400, and 500 mg/day, in a standard dose-escalation design. The MTD in patients on EIAEDs was 400 mg/day, and steady-state levels were similar to those measured in patients not on EIAEDs. Dose-limiting toxicities were prolonged QTc and thromboembolism. Thirty-two patients with recurrent glioblastoma multiforme (GBM) and 32 patients with recurrent anaplastic gliomas (AGs) were treated in the phase II trial, at a dosage of 300 mg/day on 28-day cycles. Six patients (4 GBM, 2 AG) had radiographic response. PFS6 was 6.5% in the GBM arm and 7.0% in the AG arm. Median overall survival was 6.3 months in the GBM arm and 7.6 months in the AG arm. Seizures were an unexpected toxicity of therapy. Vandetanib did not have significant activity in unselected patients with recurrent malignant glioma.

  Phase II study of sunitinib malate in patients with recurrent high-grade glioma

2011   
Journal of neuro-oncology

Receptor tyrosine kinase signaling causes profound neo-angiogenesis in high-grade gliomas (HGG). The KIT, PDGFR-α, and VEGFR2 genes are frequently amplified and expressed in HGG and are molecular targets for therapeutic inhibition by the small-molecule kinase inhibitor sunitinib malate. Twenty-one patients with progressive HGG after prior radiotherapy and chemotherapy received a daily dose of 37.5 mg sunitinib until progression or unacceptable toxicity. Magnetic resonance imaging (MRI) and dynamic susceptibility contrast (DSC)-enhanced perfusion measurements were performed before and during therapy. Cerebral blood volume (CBV) and cerebral blood flow (CBF) lesion-to-normal-white matter ratios were measured to evaluate the antiangiogenic effects of sunitinib. The most frequent grade ≥3 adverse events were skin toxicity, neutropenia, thrombocytopenia, and lymphocytopenia. None of the patients achieved an objective response, whereas a decrease in CBV and CBF within the lesion compared with the normal brain was documented in four out of 14 (29%) patients evaluable for DSC-enhanced perfusion measurements. All patients experienced progression of their disease before or after eight weeks of therapy. Median time-to-progression and overall survival were 1.6 (95%CI 0.8-2.5) and 3.8 (95% CI 2.2-5.3) months, respectively. No correlation could be established between VEGFR2, PDGFR-α, and KIT gene copy numbers or protein expression and the effects of sunitinib. Single-agent sunitinib at 37.5 mg/day had insufficient activity to warrant further investigation of this monotherapy regimen in recurrent HGG.

Stratified Phase II trial of cetuximab in patients with recurrent high-grade glioma

2009   
Annals of oncology : official journal of the European Society for Medical Oncology / ESMO

BACKGROUND: To evaluate the antitumor activity and toxicity of single-agent cetuximab in patients with recurrent high-grade glioma (HGG) after failure of surgery, radiation therapy, and chemotherapy.

patients AND METHODS: In this two-arm, open-label, Phase II study patients were stratified according to their epidermal growth factor receptor (EGFR) gene amplification status. Cetuximab was administered intravenously at a dose of 400 mg/m(2) on week 1 followed by weekly dose of 250 mg/m(2). The primary end point for this study was the response rate in both study arms separately.

RESULTS: Fifty-five eligible patients (28 with and 27 without EGFR amplification) tolerated cetuximab well. Three patients (5.5%) had a partial response and 16 patients (29.6%) had stable disease. The median time to progression was 1.9 months [95% confidence interval (CI) 1.6-2.2 months]. Whereas the progression-free survival (PFS) was <6 months in the majority (n = 50/55) of patients, five patients (9.2%) had a PFS on cetuximab of >9 months. Median overall survival was 5.0 months (95% CI 4.2-5.9 months). No significant correlation was found between response, survival and EGFR amplification.

CONCLUSIONS: Cetuximab was well tolerated but had limited activity in this patient population with progressive HGG. A minority of patients may derive a more durable benefit but were not prospectively identified by EGFR gene copy number.

Glioblastoma Recurrence after Cediranib Therapy in Patients: Lack of "Rebound" Revascularization as Mode of Escape
Emmanuelle di Tomaso1,6, Matija Snuderl2, Walid S. Kamoun1, Dan G. Duda1, Pavan K. Auluck2, Ladan Fazlollahi2, Ovidiu C. Andronesi3, Matthew P. Frosch2, Patrick Y. Wen4, Scott R. Plotkin5, E. Tessa Hedley-Whyte2, A. Gregory Sorensen3, Tracy T. Batchelor5, and Rakesh K. Jain1
Authors' Affiliations: Departments of 1 Radiation Oncology and 2 Pathology (Neuropathology), and 3 Martinos Center for Biomedical Imaging, Massachusetts General Hospital & Massachusetts Institute of Technology, 4 Department of Adult Oncology, Dana-Farber Cancer Institute, and 5 Stephen E. & Catherine Pappas Center for Neuro-Oncology, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, 6 Current affiliation: Novartis Institutes for BioMedical Research, Cambridge, MA.

Corresponding Author: Rakesh K. Jain, Steele Laboratory, COX-734, Massachusetts General Hospital, 100 Blossom Street, Boston, MA 02114. Phone: 617-726-4083; Fax: 617-724-1819. E-mail: Jain@steele.mgh.harvard.edu


Recurrent glioblastomas (rGBM) invariably relapse after initial response to anti-VEGF therapy. There are 2 prevailing hypotheses on how these tumors escape antiangiogenic therapy: switch to VEGF-independent angiogenic pathways and vessel co-option. However, direct evidence in rGBM patients is lacking. Thus, we compared molecular, cellular, and vascular parameters in autopsy tissues from 5 rGBM patients who had been treated with the pan-VEGF receptor tyrosine kinase inhibitor cediranib versus 7 patients who received no therapy or chemoradiation but no antiangiogenic agents. After cediranib treatment, endothelial proliferation and glomeruloid vessels were decreased, and vessel diameters and perimeters were reduced to levels comparable to the unaffected contralateral brain hemisphere. In addition, tumor endothelial cells expressed molecular markers specific to the blood–brain barrier, indicative of a lack of revascularization despite the discontinuation of therapy. Surprisingly, in cediranib-treated GBM, cellular density in the central area of the tumor was lower than in control cases and gradually decreased toward the infiltrating edge, indicative of a change in growth pattern of rGBMs after cediranib treatment, unlike that after chemoradiation. Finally, cediranib-treated GBMs showed high levels of PDGF-C (platelet-derived growth factor C) and c-Met expression and infiltration by myeloid cells, which may potentially contribute to resistance to anti-VEGF therapy. In summary, we show that rGBMs switch their growth pattern after anti-VEGF therapy—characterized by lower tumor cellularity in the central area, decreased pseudopalisading necrosis, and blood vessels with normal molecular expression and morphology—without a second wave of angiogenesis. Cancer Res; 71(1); 19–28. &copy;2011 AACR.

我母亲12年9月多发脑转，行全脑放30gy，12次，今年4月脑核磁发一个（0.49-1.00），坏死？这个去年就有。目前正在试特，期待有效。

有一个药物叫memantine (Namenda),可以减少脑部放疗的副作用
Can a drug reduce risk of cognitive side effects from whole brain radiation therapy?

http://cancergrace.org/radiation ... -radiation-therapy/
Last week, I wrote a post highlighting a relatively new blog and a review article about whole brain radiation therapy (WBRT) by my friend, Moffitt Cancer Center-based radiation oncologist Dr. Jacob Scott.   I found the review article to be among the very best I’ve ever encountered on this very important subject, but it only made passing reference to an important trial called RTOG (for Radiation Therapy Oncology Group) 0614, which randomized patients to WBRT with or without the agent memantine (Namenda), a medication for Alzheimer’s disease.  Memantine works by blocking glutamate receptors in the brain, which can excite brain cells, but at high levels of transmission, the effect can be harmful on memory formation and brain function.  Radiation oncologists developed the study to ask whether the this agent that can have a (modestly) beneficial effect on cognitive function on Alzheimer’s disease might also be beneficial in reducing cognitive deficits in patients who undergo WBRT.

I asked Dr. Scott for his thoughts on the recently reported preliminary results of the RTOG 0614 trial, which was among the most important results presented at the big radiation oncology conference in October of last year, called ASTRO (American Society for Radiation Oncology — I think the T is sometimes said to abbreviate “Therapeutic”, sometimes acknowledged as gratuitous to make an elegant abbreviation).  As described in a very nice follow-up post by Dr. Scott, the results suggested a borderline statistically significant result, with a p value just above our magic threshold of 0.05 that makes us more convinced that it should change our practice patterns.  

Dr. Scott offered his personal commentary on what this should mean.  I’ve had my own discussions with radiation oncologists and found, as he did, that there isn’t any clear consensus on whether these results should establish a new standard of care.  But like Dr. Scott, I think it’s a mistake to over-interpret a statistical result, whether it does or doesn’t meet a threshold of 0.05, as having some magical significance.  Particularly in trials that have smaller patient numbers (as occurred here because, unfortunately, many patients died without being able to be followed longitudinally), potentially very clinically significant results may be dismissed because insufficient numbers leave a difference with a p value that falls a little short of a line we’ve drawn as being critically important.  I’ve touched on this important issue of clinical vs. statistical significance myself and have even written a post about it, nearly 5 years ago, that comes to the same conclusion Dr. Scott reached: we shouldn’t let a p value threshold come between us and the logical acceptance of a compelling result.

Accordingly, I’m increasingly inclined to favor inclusion of memantine for my patients who undergo WBRT, and several of the radiation oncologists with whom I work share this strategy.  The challenge we then face is whether insurers are swayed enough by the results to cover memantine for patients who don’t have Alzheimer’s disease.  I haven’t had enough patients to say what to expect in this regard, but I expect that they will if this agent becomes a more universally accepted standard of care paired with WBRT.

2003年，美国FDA批准美金刚胺（memantine，Namenda）作为第一种用于治疗中、重度老年痴呆症的药物，目前FDA已经批准上市的其它4种药物只能治疗早期老年痴呆症。美金刚胺可以抑制大脑过多的谷氨酸盐，这种物质可伤害或杀死神经细胞。经证实，美金刚胺可使老年痴呆症的恶化速度减缓，让患者自行上厕所等行动维持的时间延长。III期临床试验已经表明，和安慰剂相比Namenda能够统计学明显的增强病人的认知能力和综合功能。        

商品名称：易倍申 盐酸美金刚片 28片类别： 中西药品 > 神经系统 > 痴呆

通用名：盐酸美金刚片

批准文号：注册证号H20060272有效期：

功能主治：易倍申治疗中重度至重度阿尔茨海默型痴呆。

用法用量：本品应由对阿尔茨海默型痴呆的诊断和治疗富有经验的医生处方并指导患者的使用。患者身边有按时监督患者服药的照料者的情况下才能开始治疗。应按照现行的诊断标准和指南对痴呆进行诊断。 成人：每日最大剂量20mg。为了减少副作用的发生，在治疗的前3周应按每周递增5mg剂量的方法逐渐达到维持剂量，具体如下：治疗第一周的剂量为每日5mg（半片，晨服），第二周每天10mg（每次半片，每日两次），第三周每天15mg（早上服一片，下午服半片），第4周开始以后服用推荐的维持剂量每天20mg（每次一片，每日两次）。 美金刚片剂可空腹服用，也可随食物同服。

副 作 用：本品的不良事件总发生率与安慰剂水平相当，且所发生的不良事件通常为轻中度。本品的常见不良反应（发生率低于2%）有幻觉、意识混沌、头晕、头痛和疲倦。少见的不良反应（发生率为0.1-1%）有焦虑、肌张力增高、呕吐、膀胱炎和性欲增加。根据自发报告，有癫痫发作的报告，多发生在有惊厥病史的患者。

430元一盒。

您好，麻烦帮忙看下我的贴好吗，万分感谢http://www.yuaigongwu.com/thread-10131-1-1.html

老马 发表于 2013-5-18 01:33

                               
登录/注册后可看大图

2003年，美国FDA批准美金刚胺（memantine，Namenda）作为第一种用于治疗中、重度老年痴呆症的药物，目前FD ...

老马哥，请教一下，你们家氧疗是怎么进行的？每天多久，需要面罩还是光一根管子吸氧？有什么需要注意的？谢谢