【3年】爸爸，很爱很爱你，你的爱永远陪伴我。。

爱的力量

原帖由 海蓝 于 2009-12-23 00:40 发表
安安，看完你的全贴，获益良多，感动于你的孝心，也钦佩你的坚强聪慧！加油！

虽然腺癌和小细胞的治疗方式不同，来到这里我们的心都是一样的，永不放弃，加油，祝福家人！

爸爸的女儿

安安, 我觉得邵医生是以肿瘤内科擅长的, 骨科的治疗还是要谨慎, 不能完全听他的.

爱的力量

Everyone is now familiar with the success stories of targeted agents in cancer therapy. A new promising targeted agent is Pfizer drug PF02341066, the story of which may be more analogous to the development of Gleevec (imatinib)or Herceptin (trastuzumab) than to Tarceva Tarceva. Both of the former drugs were tested in selected patients, with the idea that we knew which patients were likely to benefit. This is in contrast to Tarceva, which was tested in unselected patients and found to benefit a subset; it was only afterwards that investigators identified the critical importance of EGFR mutations.

   At the recent ASCO meeting, Dr. Eunice Kwak presented fascinating results of a trial in which a novel agent was tested in patients selected because of a known genetic abnormality in their lung cancers.   To provide a little background, the EML4-ALK fusion gene was identified in 2007 by a group of Japanese investigators headed by Dr. Hiroyuki Mano, who identifed a novel fusion gene from a surgical specimen of a patient with lung adenocarcinoma. The EML4 gene and the ALK gene, which are normally separate from each other but both on chromosome 2, had become fused together in this patient’s cancer. This fusion results in increased activity of ALK, which was already known to be implicated in a certain type of lymphoma.  The authors subsequently found that this fusion gene was present in the tumors of other patients. When they put this gene into cells and then put the cells into mice, the mice developed tumors. In the lab, they tested an inhibitor of ALK against cancer cells with this fusion gene and found that it dramatically inhibited their growth.   Subsequent studies have identified that patients with the EML4-ALK fusion gene tend to be younger than the average lung cancer patient, are more likely to be light or never smokers, and have adenocarcinomas. While these clinical characteristics are also shared by patients with EGFR mutations, patients with EML4-ALK do not have EGFR mutations.

   In another ASCO 2009 abstract, Dr. Alice Shaw and colleagues performed a retrospective study of the frequency of EML4-ALK in patients with these clinical characteristics. They found that 13% of the 141 patients in their sample had this fusion gene. The patients with the fusion gene were younger (average age 52 vs. 64 in those who didn’t have the mutation) and were more likely to be male. None of the patients with EML4-ALK had responded to treatment with Tarceva or Iressa. However, patients with EML4-ALK were just as likely to respond to chemotherapy and their 1-year survival was similar to other patients in the group.

   In the presentation referenced above, Dr. Kwak and colleagues initially conducted a first-in-human study to determine the maximum tolerated dose of the drug. One patient in that initial group (a 49-year-old man) had an EML4-ALK lung cancer. He had a dramatic response to treatment, coming off oxygen after receiving the drug. The side effects of the drug overall were overall mild: nausea, fatigue and liver enzyme elevations the most common. The next phase of the study included only patients with ALK fusions. Out of 19 patients, over 50% had a response to treatment and 80% had either a response or stable disease. These results are especially impressive given that most of the patients had received numerous previous treatments for their lung cancers. On the basis of these promising results, a large phase III study of PF02341066 is planned to further evaluate this drug for patients with EML4-ALK lung cancer.

   The story of EML4-ALK lung cancer is a new and important one, and it gives us a glimpse into a future where the idea of treating all patients with NSCLC the same way will be preposterous. This all started with an analysis of a single patient’s tumor and is one of the most elegant examples of translational research and personalized medicine that I have seen: a discovery going from a patient to the lab and back to patients, all within the space of two years.

    I’m looking forward to seeing more of this.  Lung cancer needs a Gleevec.

一个身在日本的病友分享的重要信息，值得期待，我会稍作翻译。

碱性健康人

安安，很高兴阿瓦斯丁见效了，这个邵医生真让我们又爱又恨啊，不过，他对骨转移射频消融还是信心爆棚的，我还是比较相信他，当时我家小爱有骨痛，差点想搞去给他做一下了，用他的话说是“一劳永逸”，比放疗好多了。好在现在小爱不痛了，也不用去找他了。

如果说保健品方面对小爱的帮助，我认为大量的钙镁片是功臣，自从他有痛症后，我一直在蔬果汁里加三片安利的钙镁片，每天三杯，就是九片了。出院后没多久就停用止痛药了。

还有其它很重要的方法，这里不多说了，希望你爸有好的治疗效果，不必东奔西跑吧。。。路程近还可以考虑，太远了就太折腾，风险非常大。。。最后小爱还是没去香港看邵医生，一直是我给他买药的。

上面的信息，等待你的译文了。。。简单一点就行了，说出关键的东西。

爱的力量

如今大家都非常熟悉靶向药物在治疗癌症上取得的重大成果。一个新兴的有重大意义的靶向药物就是辉瑞的新药PF02341066. 这个发现类似于格列卫和赫赛汀相比于特罗凯。（根据作者的语气，应是认为此药的意义远超特罗凯。）格列卫和赫赛汀都是选择了认为会受益的目标人群进行实验。相比于特罗凯，是广泛实验再发现受益的子群，后来研究人员才明确关键在于EGFR基因的突变。
最近ASCO会议上，肖博士发布了一种新的靶向药物在已知基因变异优选肺癌病人身上产生的惊人的效果。首先提供一些背景，EML4-ALK混合基因在2007年被一个日本研究团队发现，研究者从一个肺腺癌患者的病理样本中发现一种新型的混合基因，EML4基因和ALK基因，正常情况下是分开的但都存在于2号染色体上，在这个患者身上基因融合在一起。融合导致了ALK的激增活动，之前已经发现可以导致某种淋巴癌。作者逐渐发现混合基因存在于其他病人的肿瘤种。当他们把基因片段植入小鼠，小鼠迅速生长肿瘤。实验中，他们实验了一种ALK的抑制剂发现大幅抑制了肿瘤的生长。随后的研究他们界定出EML4-ALK基因突变的病人倾向于比平均病患年龄年轻，不吸烟或少量吸烟的腺癌患者。虽然他们和EGFR的目标人群临床特性吻合，但是有EML4-ALK基因变异的患者没有EGFR基因变异。
（这样说来，目标人群，但是易瑞沙特罗凯都无效的，或者说是易瑞沙特罗凯快速耐药的人会是最有可能的受益人群。）
在肖博士的一次关于EML4-ALK变异几率的回溯研究中。他们发现141个病人中有13%有这个混合基因。病人平均年龄52（没有这个变异的平均年龄是64），更多的是男性。没有一个带有EML4-ALK的病人对易瑞沙或特罗凯响应。TOT..然而，带有EML4-ALK变异的病人对于化疗的响应和1年生存期都等同于其他病人。
在以上的陈述中，肖博士首先在人体实验开展了最大耐受剂量的决定。一个49对的男性肺癌病人带有EML4-ALK，在用药后戏剧性缩小并脱离氧气。副作用总体来说算是温和的，恶心，疲劳，肝损都是总体常见的。下一期实验只包括有ALK混合病人。在19个病人中，超过50%对于药物响应，80%稳定或响应。实验结果非常令人鼓舞的是大部分病人在此前都接受过长期各种的治疗。在这个基础上将开展3期试验。
关于这个新基因的发现，更我们一个更清晰的景象未来的非小细胞肺癌的治疗会根据病人状况定制，更让我看到了2年时间，从单个病人的分析到实验室再到病人，这个惊人的速度。
我期待看到更多的消息，肺癌太需要一个“格列卫”了。
（格列卫不太了解，应该是可以给病人一个相对非常长期的稳定时间，让我来说，我更希望肺癌有一个“胰岛素”）END

爱的力量

原帖由 爸爸的女儿 于 2009-12-23 10:36 发表
安安, 我觉得邵医生是以肿瘤内科擅长的, 骨科的治疗还是要谨慎, 不能完全听他的.

lily姐，我也是浅听则止，这个问题是非常的复杂了，要说后悔只能是易瑞沙耐药到上力比泰中间经历2次放疗，一次手术，过了个春节，硬是拖到了很难挽回的损伤，现在我也只能走一步看一步，没保住家人的生活质量，这一点我很失败。

爱的力量

原帖由 碱性健康人 于 2009-12-23 22:36 发表
安安，很高兴阿瓦斯丁见效了，这个邵医生真让我们又爱又恨啊，不过，他对骨转移射频消融还是信心爆棚的，我还是比较相信他，当时我家小爱有骨痛，差点想搞去给他做一下了，用他的话说是“一劳永逸”，比放疗好多了。 ...

小爱太太，想多跟你交流一下治疗上的问题，呵呵，看你的记录还是温情的多，治疗的少。现在你们小爱主要在用什么治疗维持，我爸爸这个问题不是普通的骨部问题了，胸椎，腰椎，骶椎这些都是会影响到神经的，所以非常的麻烦，我觉得邵也是搞不定的。补钙的问题，因为我们持续在用双磷酸盐，里面的禁忌症也写明禁高钙，所以我一直不敢贸然补钙，望多交流，加我QQ吧，在下面签名档。

legenddad

格列卫针对的也是一个融合基因ABL-BCR,不过用于慢粒白血病,还有这个病几乎所有病人都有这个基因,它才真正称的上是靶向药,五年生存率很高的,现在发现对胃肠间质瘤也有效,好了去学习了,期待