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WZ4002,延缓因T790M突变导致易、特、2992的耐药及耐药后的选择

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272563 331 又一个五年 发表于 2012-12-2 10:56:35 | 精华 |
phpinfo  大学二年级 发表于 2013-2-16 16:15:14 | 显示全部楼层 来自: 北京
这个药看来是还没有进入到一期临床吧 如果大家有人已经在用 麻烦发泄使用的经验和注意给大家参考参考吧
改变生活  初中二年级 发表于 2013-2-20 16:24:55 | 显示全部楼层 来自: 海南
可否设想一下,如果用易得同时使用WZ4002,这样可以抑制T790M突变,同时抑制EGFR原突变?
老马  博士一年级 发表于 2013-2-20 23:44:25 | 显示全部楼层 来自: 浙江杭州
大家好!我是来自于纽约纪念斯隆-凯特林癌症中心的Mark Kris。我想和大家深入讨论一下关于肺癌疾病进展方面的话题。这是一个常见的问题。我们每天都会碰到疾病进展,但仍然缺乏关于疾病进展定义和分配的关键评估。病例多种多样。在上次的讨论中,我提到了针对接受传统化疗方案患者进展标准的使用。
那么对于接受靶向药治疗的患者又该如何评价呢?首先,我们必须记住,这些肺癌病人与其它病人有所区别。他们的肿瘤细胞依赖于EGFR或者alk信号通路,这也是我们在肺癌中发现的两种最常见的类型。
这些肿瘤是由各种具有不同分子通路的细胞组成。部分细胞含有野生型基因或者单座位野生型等位基因。其它细胞含有突变基因。只有少量基因在耐药的时候发生第二突变或者耐药突变。事实上,当我们首次检测到与耐药相关的突变时,它们仅是所有EGFR等位基因中的一小部分。仍有大量的肿瘤细胞对药物敏感,此时如果我们停止使用靶向药,这些肿瘤细胞将会更快地增殖。
基于实验室试验和病人情况观察可以得出结论,EGFR耐药突变(T790M突变)的肿瘤细胞相对于EGFR敏感肿瘤细胞来说其生长速度较慢。假如我们停止服药TKI,耐药的肿瘤细胞将会继续缓慢生长。他们只占肿瘤组织中的一小部分。那些EGFR抑制剂敏感肿瘤细胞则快速增殖。很多人见过类似快速增殖,就象“耀斑现象”。
这些生物学知识,与我们以往在医学院学到的肿瘤知识截然不同,我们应该怎么办呢?正如在化疗治疗中,当出现全身转移,出现一个新的病灶时,我们需要修改化疗方案。对于EGFR-TKI治疗,情况有所不同
如果只是主病灶发生改变的情况又该如何?请记住当我们使用的是RECIST标准时,是基于肿瘤最小尺寸来判断,20%的增加意味着进展。如果是一个8cm的肿瘤,经过治疗缩小到2cm,然后又增加到了2.4cm,这也意味着符合RECIST标准的进展。
我们知道不同的病人基因类型不同,治疗过程也不一样。在座的很多人都碰到这样的患者,他们仅有一个病灶,且多年来的增长都非常缓慢。对具有这种情况患者停药可能将会对患者造成伤害。相同的标准在化疗治疗中也非常重要。你需要确定你的病人没有明显症状,而且他仍能够耐受这种药物。如果满足上述标准,对于单纯的主病灶增大的病人,应继续使用EGFR抑制剂,同时我们也应小心地保持评估、观察和影像检查。
对于决定更换治疗方案的患者,持续服用EGFR靶向药或类似能抑制EGFR信号通路的替代药物是非常重要的。目前在美国,我们只有特罗凯一种EGFR抑制剂可用。以后,我们会拥有更多的EGFR抑制剂,更换为另一种EGFR抑制剂或许可行。但目前,我们只能继续服用特罗凯。
如果你认为一位病人出现新的病灶或者新的症状需要除了厄洛替尼外的其他治疗,可进行局部治疗例如脑转,或者联用一种新的药物。
不幸的是,正如肿瘤学中的很多案例,肿瘤进展非常复杂,很难用一个词来描绘。当一个病人的影像学显示进展,你需要通过了解他初始治疗前后的肿瘤分子生物特征而做出最佳选择。

点评

谢谢老马!  发表于 2013-2-22 11:48
个人公众号:treeofhope
老马  博士一年级 发表于 2013-2-22 01:36:59 | 显示全部楼层 来自: 浙江温州
本帖最后由 老马 于 2013-2-22 13:17 编辑

Fighting over molecules
By Steven Syre
Some fights start over the smallest things. This one is about a molecule called WZ4002.
There is no shortage of people and powerful organizations fighting over the molecule, discovered by Boston scientists at the Dana-Farber Cancer Institute; it could be worth a fortune as a new treatment for many lung cancer patients.

Then again, WZ4002 could turn out to be a big nothing. It’s too early to tell.

But no one is waiting around to find out, and recent lawsuits offer a rare public glimpse of a fight over medicine and money that usually takes place behind closed doors.

Drug giant Novartis International Pharmaceutical Ltd. is locking horns with the scientists who discovered WZ4002. Those researchers are at odds with the president of the company they formed to represent their commercial interests. Dana-Farber is caught awkwardly in the middle, with important interests of its own at stake.

The conflict is remarkable because the molecule is nowhere close to becoming an approved drug. It has not been the subject of a single clinical trial. It’s still a compound in a lab, not a therapy.

John Mirick, a lawyer for researcher Nathanael Gray and three other Dana-Farber scientists behind WZ4002, says development of the molecule has been treading water since the licensing dispute broke out last year.

That would be bad news for patients, the real people at the heart of this story. Jamie Gorenberg has paid close attention to the development of WZ4002 because her mother, Caren Gorenberg, suffers from advanced lung cancer. She recognizes it’s a long shot but hopes the molecule might help her mother in a clinical trial someday soon.

“I know that’s a big if, but we live on ifs,’’ says Gorenberg. “That’s better than nothing, and I’m going to grab onto it.’’

Gorenberg learned about WZ4002 by reading an article in the scientific journal Nature in December 2009 that described how the molecule could help patients with non-small cell lung cancer who also have common gene mutations. Those mutations help the cancer resist the leading treatments, and WZ4002 might get around that problem.

The article in Nature also came as news to executives at Novartis, which spends more than $15 million a year on sponsored research at Dana-Farber, according to court papers. The drug company funded some work in Gray’s lab, and executives soon pressed Dana-Farber for rights to WZ4002. Their view: Novartis owned those commercial rights.

That was a big problem because Dana-Farber gave an option for the rights to Gatekeeper Pharmaceuticals Inc., a company formed by Gray and his colleagues. The cancer institute filed a patent application for WZ4002 but was stuck between the commercial interests of its scientists and a big research sponsor.

Dana-Farber’s solution: Sue and let US District Judge David Woodlock decide who owns what.

“We are not seeking any monetary award,’’ Dana-Farber said in a statement yesterday. “We are simply asking the court to determine which of the two parties has the superior rights to the technology.’’

Meanwhile, the scientists who formed Gatekeeper didn’t see eye to eye with John Chant, whom they hired to run the company and advance the commercial interests of WZ4002.

Chant didn’t like the company’s legal strategy. He made the ambitious argument that Gatekeeper’s founders, who owned 87 percent of the company and constituted its board, were conflicted in the case because they worked at Dana-Farber, among other reasons.

Chant wants to intervene on behalf of Gatekeeper and pursue another legal strategy.

Gray and his colleagues say they are open to a settlement with both Novartis and Dana-Farber. Chant wanted to fight for damages and insisted any settlement must include $750,000 to cover deferred and future compensation for him, according to court papers filed by the scientists.

“The board concluded Mr. Chant was primarily concerned for his salary and benefits,’’ they said in the documents.

Strange fact: Chant is still employed by Gatekeeper.

Chant’s lawyer did not return a call yesterday.

Now the judge has to figure it all out or push for a settlement. But time matters.

“All I can say is, move quickly,’’ Gorenberg says. “I’m not trying to blame anyone or point fingers.’’

The molecule in question may save lives, though the odds are long. But no one will figure that out until everyone agrees on who owns WZ4002.

http://www.boston.com/business/h ... ust_wait_for_cures/

点评

让他们打去吧,我们试我们的。  发表于 2013-2-22 11:50
个人公众号:treeofhope
又一个五年  高中一年级 发表于 2013-2-22 12:07:09 | 显示全部楼层 来自: 山东

WZ4002可以同时抑制易瑞沙的靶点和T790M新突变,因此在对付易瑞沙的靶点上可以取代易瑞沙和特罗凯,但是为了延长生命,应该还是先用易瑞沙为好,等耐药了再用4002,4002用一段时间也会耐药,出现新突变的。

假如EGFR突变直接上4002,有效时间会比易+特+2992+4002长吗?相信没人敢尝试,只有等科学家们的试验报告了。

点评

你好, 能否告诉我4002购买途径,谢谢  发表于 2013-3-12 23:32

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fred9999  小学六年级 发表于 2013-2-22 18:09:48 | 显示全部楼层 来自: 英国
这个网站订靠谱吗?
selleckchem

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那是标准品,超贵的。  发表于 2013-2-23 16:21
老马  博士一年级 发表于 2013-2-23 16:04:30 | 显示全部楼层 来自: 浙江温州
本帖最后由 老马 于 2013-9-6 10:29 编辑

CO-1686与WZ4002结构类似,同属第三代EGFR抑制剂。
http://cancergrace.org/topic/afa ... -user-group/page/5/
MTD has not been reached in the CO-1686 trial. The dose started at 150 and I know someone on 900mg! The good news is there are virtually no side effects (some muscle pain?)。
--------------------------------------------------------------
CO-1686 – problem seems to be with its short half-life, so they’re now working on revising dosing schedules, as very high doses have been reached but it’s in and out of one’s body much too quickly. No side effects still, so that’s good,
-------------------------------------------------------------------------------------------------------------------------------------
The current dose cohorts (still in dose-escalation phase) are 1200mg once, twice, and three times a day (3 patients per dosing schedule).
There are currently 9 people on their waiting list (I’m #9), with new cohorts opening roughly every two months.
-------------------------------------------------------------------------------------------------------------------------------------------
Unfortunately, the Clovis trial has not reached MTD。
--------------------------------------------------------------------------
CO-1686的动物剂量是WZ4002的4倍(100mg/kg比25mg/kg),半衰期比较短,临床设计方案有三种:每天一次,每天二次,每天三次,目前1期临床试验已经爬坡到1200mg每天,仍然没有观察到明显副作用。
建议WZ4002的服用剂量:
150毫克每天,每天3次,一次50毫克。
如果一天3次难以依从,也可以用1天二次,一次75mg.
=====================================
现在的推荐剂量是300mg每天,一天二次,一次150mg.
个人公众号:treeofhope
fred9999  小学六年级 发表于 2013-2-23 17:58:04 | 显示全部楼层 来自: 英国
谢谢老马和又一个五年
dashan666  初中二年级 发表于 2013-2-27 12:34:59 | 显示全部楼层 来自: 天津
感谢楼主,学习了,我父亲服易17个月耐药了,现喘的厉害,服特5天,急需WZ4002试药,求各位大侠告诉渠道啊!HELP!
QQ:419158173  fdy9902@sina.cn
我爸爸67岁肺腺癌易瑞沙一线控制良好
http://www.yuaigongwu2012.com/for
dashan666  初中二年级 发表于 2013-2-27 22:52:56 | 显示全部楼层 来自: 广东深圳
dashan666 发表于 2013-2-27 12:34
感谢楼主,学习了,我父亲服易17个月耐药了,现喘的厉害,服特5天,急需WZ4002试药,求各位大侠告诉渠道啊! ...

谢谢楼主的指导,收益颇多。
QQ:419158173  fdy9902@sina.cn
我爸爸67岁肺腺癌易瑞沙一线控制良好
http://www.yuaigongwu2012.com/for

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