Clin Lung Cancer. 2012 Jan;13(1):24-30. doi: 10.1016/j.cllc.2011.05.007. Epub 2011 Aug 10.
Brain metastases as the primary site of relapse in two randomized phase III pemetrexed trials in advanced non-small-cell lung cancer.
Ortuzar W, Hanna N, Pennella E, Peng G, Langer C, Monberg M, Scagliotti G.
SourceEli Lilly and Company or one of its subsidiaries, Indianapolis, IN 46285, USA. ortuzarwa@lilly.com
Abstract
BACKGROUND: Symptomatic brain metastases (BM) frequently occurs after initial treatment of non-small-cell lung cancer (NSCLC). Therefore, 2 large randomized trials that involved pemetrexed were retrospectively analyzed to determine the pattern of symptomatic relapse in the brain and to gauge if pemetrexed could influence the incidence.
METHODS: Two large phase III studies of pemetrexed in advanced NSCLC were included. One study compared pemetrexed with docetaxel in previously treated patients (n = 571); the other study tested cisplatin plus pemetrexed vs. cisplatin plus gemcitabine in chemotherapy-naive patients with advanced NSCLC (n = 1725). Patients with known BM at study entry were excluded from this analysis. Each study was analyzed separately, then jointly to determine the rate of BM reported as the only site of progressive disease by treatment group and histology. Logistic regression was used to obtain an odds ratio for the treatment effect on the overall occurrence of BM while controlling for potential confounding factors.
RESULTS: Overall, 71.5% of patients in pemetrexed-containing arms (819 of 1145), and 68.2% of patients in non-pemetrexed-containing arms (785 of 1151) experienced progressive disease. BM recurrence rates were 3.2% (95% confidence interval , 2.1%-4.6%) in the pemetrexed-containing arms vs. 6.6% (95% CI, 5.0%-8.6%) in the non-pemetrexed-containing arms (P = .002). The odds ratio for BM recurrence associated with exposure to pemetrexed was 0.49 (95% CI, 0.32-0.76; P = .001). The beneficial effect of pemetrexed on BM was confined to patients with nonsquamous NSCLC.
CONCLUSIONS: Patients with advanced nonsquamous NSCLC treated with pemetrexed either in first-line or second-line therapy may reduce the risk of developing BM as the first site of progressive disease. This retrospective analysis is limited due to the lack of baseline and periodic brain scans, and it reflects symptomatic BM only. Regardless, these findings suggest a potential beneficial effect of pemetrexed-based treatments on the control of BM.
http://www.ncbi.nlm.nih.gov/pubmed/21831719
Outcomes associated with brain metastases in a three-arm phase III trial of gemcitabine-containing regimens versus paclitaxel plus carboplatin for advanced non-small cell lung cancer.
Edelman MJ, Belani CP, Socinski MA, Ansari RH, Obasaju CK, Chen R, Monberg MJ, Treat J; Alpha Oncology Research Network.
SourceUniversity of Maryland Greenebaum Cancer Center, Baltimore, Maryland 21201-1595, USA, medelman@umm.edu
Abstract
BACKGROUND: Brain metastases (BMs) are a common complication of non-small cell lung cancer (NSCLC). Because of historical data indicating a poor prognosis for patients with BM, few randomized phase III studies of advanced NSCLC have included patients with BM at presentation. Because the potential benefits of systemic therapy in patients with BM are uncertain, we analyzed data from a recent phase III study.
METHODS: One thousand one hundred thirty-five chemonaïve patients with stage IIIB/IV NSCLC were randomized to receive gemcitabine/carboplatin, gemcitabine/paclitaxel, or paclitaxel/carboplatin. Stratification was based on presence or absence of BM, stage, and baseline weight loss. Patients with BM were required to be clinically stable after treatment with radiotherapy or surgery before entry. Results were retrospectively analyzed by presence or absence of BM at study entry.
RESULTS: Rate of BM was 17.1% overall. The response rate was 28.9% for patients with BM (n = 194) versus 29.1% without BM (n = 941). Time to progression was 4.3 months with BM and 4.6 months without BM (p = 0.03). Median survival was 7.7 months (95% confidence interval: 6.7-9.3) among patients with BM (n = 194) and 8.6 months (95% confidence interval: 7.9-9.5) for patients without BM (n = 941), p = 0.09. Rates of hematologic adverse events were not different among patients with and without BM.
CONCLUSIONS: There were no significant differences in response, survival, or hematologic toxicity for patients with or without BM; however, patients with BM had a small but significantly shorter time to progression. Nonprogressing patients with treated BM are appropriate candidates for systemic therapy and entry into clinical trials.
http://www.ncbi.nlm.nih.gov/pubmed/20035187
Continuous pemetrexed treatment for brain metastasis in non-small cell lung cancer-A report of two cases.
Nobuaki Ochi, Hiromichi Yamane, Tomoko Yamagishi, Nagio Takigawa
Department of General Internal Medicine 4, Kawasaki Medical School, Okayama, Japan.
Lung cancer (Amsterdam, Netherlands) (Impact Factor: 3.14). 12/2012; DOI:10.1016/j.lungcan.2012.12.010
Source: PubMed
ABSTRACT Brain metastasis is a major complication in patients with advanced non-small cell lung cancer (NSCLC), which is the malignancy that metastasizes most frequently to the central nervous system (CNS). Although the CNS is protected from cytotoxic agents by the blood-brain barrier under normal conditions, the blood-brain barrier is thought to become less functional in the presence of brain metastasis. Here, we describe two NSCLC patients who relapsed with brain metastases. Following brain stereotactic irradiation, salvage chemotherapy using pemetrexed was given. Continuous pemetrexed treatment resulted in no recurrence, including brain metastasis, over 2 years without whole-brain irradiation. Our experience suggests that pemetrexed suppresses brain metastasis after stereotactic irradiation.
http://www.researchgate.net/publication/234031329_Continuous_pemetrexed_treatment_for_brain_metastasis_in_non-small_cell_lung_cancer-A_report_of_two_cases
ACR Appropriateness Criteria® multiple brain metastases.
http://www.guideline.gov/content.aspx?id=35161
请教老马老师，本人2010年底发现肺腺癌早期，进行了根治手术，四次吉西他滨加顺铂的化疗，此后一直吃中药，今年9月复查发现小脑单转（其他部位均好），又进行了切除手术，然后又进行了2次化疗（紫杉醇加顺铂）。进行了基因检测，EGFR基因21外显子突变。现在想吃靶向药。想请教一下：1、现在体内无病灶，抗原指标也一直正常，吃正版靶向药可以获赠吗？2、吃易瑞沙还是特罗凯？3、吃鸦胆子油有用吗？
不平则鸣 发表于 2013-11-28 21:03 static/image/common/back.gif
请教老马老师，本人2010年底发现肺腺癌早期，进行了根治手术，四次吉西他滨加顺铂的化疗，此后一直吃中药， ...
谢谢回复！我主要是担心如果今后复发治疗难度更大，所以想象憨叔那样吃靶向药把癌细胞控制住不让他复发。这样是否比出现病灶再上靶向要好。此外，我现在已做了两次化疗（紫杉醇加顺铂），是否有必要做完4次？如果有脑转，特罗凯的效果是否更好？再次谢谢马老师！
yezi 发表于 2011-10-15 22:00 static/image/common/back.gif
我妈妈一直是脑转的问题控制不住，所以很感谢老马开了脑转治疗专贴。借这个帖子简单描述下我妈妈脑转用过的 ...
楼主你好，你妈妈当时脑转是什么症状啊，放疗后吃特效果很明显啊？我妈今天化疗第二天，用的是卡莫司汀，不知道此药效果如何，医生建议先化疗然后局部放疗，我想如果化疗效果好，是否可以试试特呢，我妈基因无突变不知道可否试特呢？因为肺转移头，我很害怕耽误治疗，您给看看如何是好呢？
snow0371 发表于 2013-11-15 10:31 static/image/common/back.gif
帖子全部看完了，谢谢老马为我们大家的辛勤付出，可惜最近几天才注意到到妈妈全脑放疗后继发的语言障碍、肢 ...
全脑放的后遗症是什么时候体现出来的呢？为什么给我妈看病的医生说他从医这么久没发现全脑放就立马傻的，大概都是过十年二十年才会体现出来的，真是这样吗
snowswan721 发表于 2013-12-7 23:07 static/image/common/back.gif
楼主你好，你妈妈当时脑转是什么症状啊，放疗后吃特效果很明显啊？我妈今天化疗第二天，用的是卡莫司汀， ...
其实全脑放疗并没有用够全量，一般大夫会用总量的80%，还留20%这剩下的计量是给大病灶单个治疗准备的，我妈妈全脑放疗完以后有些后遗症，肢体没以灵活了（也许是脑水肿的原因），单个放疗（射波刀）做了三次，一次是脑、一次纵膈和肺、一次肝脏，历时一年多（每次放疗中间也需要休息），现在行动越来越不好了基本上卧床了，具体是因为病情还是因为放疗这个我不能完全定性，但是我们去做射波刀，上海复旦大学射波刀中心的大夫跟我们说，现在放疗的有一种趋势就是长一个做一个这样病人的生活质量高，当初我们做全脑放疗的时候也不知道有射波刀这样的手段，当时做全脑放疗的时候主要考虑的是把脑部能够看到的和看不到的小病灶都控制一下，现在妈妈脑部稳定，但是生活质量的确不高，我们要求也不高人在就行了，能看到她大家都很觉得很开心，即使是现在如果能够从新选择具体做不做全脑放疗我估计我仍然会纠结。
罗氏的Brain Shuttle技术
http://www.roche.com/research_and_development/what_we_are_working_on/research_technologies/protein-related_technologies/brain_shuttle.htm
Brain Shuttle is a technology that we have developed at Roche to increase penetration of large molecules such as antibodies into the brain. Access of large molecules to the brain is restricted by the blood brain barrier (BBB), a gatekeeper between the blood and the brain tissue that carefully filters which molecules can enter the brain. By using the Roche antibody engineering platform, we have created antibodies that are able to cross the blood brain barrier by binding to one of the protein receptors located on its surface. The so-called “brain shuttle” technology could potentially transport all types of therapeutic molecules into the brain, regardless of their intrinsic ability to cross the blood brain barrier.