[转]对于EGFR突变的肺癌病人，减量服用特罗凯可能仍然有效

对于EGFR突变的肺癌病人，减量服用特罗凯可能仍然有效
原贴地址：
http://cancergrace.org/forums/index.php/topic,9491.0.html
我翻译了主要的回贴，大家一起讨论一下。
Jo from Aust（发贴时间2011年5月）：
Hi all
Some good news to share.
I will briefly recap Mums situation. Diagnosed with Adenocarcinoma June 2006 (left Lung removed).
In June 2009 cancer returned to right lung. Started Chemo..4 rounds of Carbo/Gem. Stable until April 2010.
Started Tarceva 150mg ..only took it for 15 days and ended up in hospital..(see older posts). Dr reduced Tarceva to 100mg..same outcome..could not tolerate side effects...
Started Alimta July 2010 to December 2010..Stable,
Feb 2011 tumors stated growing.
As a last option Dr. put Mum back on Tarceva..25mg. For the last 3 months there have been no side effects and she is feeling very well. CT Scans done last week show Tarceva has reduced her tumors by 40 percent. Can't say how    happy we all are....Mum always had a feeling that she wanted to try Tarceva at a lower dose so at least she did and no matter what happens in the future at least we know we tried.
分享一些好消息.
我先简要地回顾一下妈妈的情况。2006年6月确诊腺癌，左肺切除。2009年6月右肺转移，经过四个疗程的健择/顺铂，有效，2010年四月进展，开始用特罗凯，150mg/d，15天后医生建议减量到100mg/d，结果还是无法耐受副作用。2010年6月到12月，应用力比泰，稳定。
2011年2月肿瘤进展。作为最后的选择，医生建议用回特罗凯，25mg/d。最近3个月她感觉很好，没有副作用。上周CT检查显示肿瘤缩小了40%。
Dr West（回贴时间2011年5月）：
That's truly wonderful.  I don't know if she has an EGFR mutation, but we do see that many patients with an EGFR mutation are particularly sensitive to the side effects of the EGFR tyrosine kinase inhibitors but also can respond very well to much lower than standard doses of them.  I think it's very helpful to try to educate patients and physicians about how to manage the side effects and dose reduce as needed, so that they don't abandon an EGFR inhibitor prematurely, but this is particularly true for the patients who may be exquisitely sensitive to the good and bad effects of them.

   Good luck to her!

-Dr. West
这真是太棒了。我并不知道她是否有EGFR突变，但我们确实看到许多EGFR突变的病人对EGFR酪氨酸激酶的副作用特别敏感，比标准剂量缩小很多时仍然如此。我认为这是非常有益的尝试，指导病人和医生如何协调副作用和剂量的关系，让他们不要过早放弃EGFR抑制剂，这对正副作用特别敏感的病人尤其如此。

祝她好运！


ssflxl:

ssflxl:
                good for your mom.  I have been on 25mg Tarceva since Feb and it has done very well for me.  When I asked my onc about data on low dose or optimal dose, she told me there is really no good data comparing dosages.  the dose is not based on weight either.  But there are small groups of people who respond well to low dose, and I am one of them.  I have the EGFR mutation and just "looking" at the pill gives me a rash!!!  I still have some inflammation on my scalp and face on 25mg, but that's so much more tolerable!!  so good luck!!
（Never smoker, Asian woman, Stage 4 NSCLC, EGFR + (exon 21 - L858R) - strange metastasis to soft tissue in paraspinal area, given Radiation - 11/2010 and started on Tarceva 150mg in Nov 2010.  Decreased dose of Tarceva to 25mg/day in Feb 2011 due to side effects.  PET in 5/2011 showed much decrease in size and uptake of the left lung mass and the paraspinal mass is no longer visible.）
你妈妈的消息不错。我从今年2月开始服用25mg/d的特罗凯，效果不错。我询问过医生关于小剂量或最佳剂量的事，他说目前关于剂量比较的数据并不充分，而且剂量与体重无关。但目前有小部分人使用小剂量效果不错，我也是其中之一。我的EGFR突变，使用标准剂量给我大量皮疹。我使用25mg/d的剂量后仍然有少量皮炎在头皮和脸上，但已经舒服多了。
graceabchen:
Following is a direct quote from a research report in CLINICA CARE OPTIONS: “none of the previously mentioned studies evaluated the efficacy of the reduced doses of erlotinib compared with the standard dosing of 150 mg/day. However, preliminary data from smaller retrospective analyses and case reports suggest that patients who require dose reductions due to treatment-related toxicities demonstrate better clinical outcomes. For example, in a retrospective single-institution study reported by Binder and colleagues (Med Oncol. 2010), among 53 patients with advanced NSCLC who were treated with erlotinib, the median TTP was 3.1 months for those patients who tolerated the 150 mg/day dose of erlotinib, 6.2 months for those who tolerated a 100 mg/day dose, and 18.4 months for those patients who could only tolerate a 25 or 50 mg/day dose level. Similarly, the median OS was also longest in those patients who were able to tolerate only the 25 or 50 mg/day dose level. In another retrospective study of 7 patients with advanced EGFR-mutated NSCLC, Yeo and colleagues (J Thorac Oncol. 2010;5:1048-1053) reported a 71.5% response rate and median PFS of 17 months (95% CI: 6-35) at an erlotinib dose of 25 mg/day).”
The above information seems to suggest that smaller dose of Tarceva gets better result. Am I having a wrong impression? Faculty members, please help resolve this puzzle.
(stage-4 NSCLC with EGFR mutation (exon 19), on Taceva as first line 10/2010, has regained physical strength with manageable side effects, PET/CT in 4/2011 showed significant improvement, PET/CT in 8/2011 showed stable condition with a small improvement: bone mets gone and no new lesions or new adenopathy.)

以下内容是临床研究报告的直接引用：以往的研究并没有评估与标准剂量为150mg/d相比，厄洛替尼减少剂量的疗效。然而，从较小的回顾性分析和病例报告的初步数据表明，因为副作用的关系而减少剂量的病人表现出更好的临床结果。Binder和他的同事在一个回顾性的小规模单机构研究中报道了53名服用厄洛替尼的晚期非小细胞肺癌病人，服用150mg/d标准剂量的病人的中位进展时间（TTP）为3.1月，服用100mg/d剂量的病人的中位进展时间（TTP）为6.2月，服用25mg/d或50mg/d剂量的病人的中位进展时间（TTP）为18.4月。
同样，这批只能耐受25mg/d或50mg/d剂量病人的中位生存期最长。在另一个回顾性研究中，Yeo和他的同事报道了7名EGFR突变的晚期非小细胞肺癌病人，服用25mg/d剂量厄洛替尼，有效缓解率71.5%，中位无进展生存期为17月。

Dr West：
I don't think a higher dose necessarily accelerates acquired resistance.  Rather, I think there are several potential factors.  First, many people with an EGFR mutation seem to be exquisitely sensitive to both the favorable effects of Tarceva (erlotinib) as well as the side effects, so most of the people who require dose reductions down to 25-50 mg daily probably have a mutation.  I would be very dubious that the same results of good benefit at very low doses holds true for a population of people who don't have an EGFR mutation, so the country of origin of these publications speaks to the high prevalence of an EGFR mutation there.  I wouldn't presume at all that these results hold true in a population that doesn't predominantly include people with an EGFR mutation.
  
   Second, it typically takes several months to gradually drop the dose all the way down to 25-50 mg/day, so I suspect that many people who get down to this dose will have already been on Tarceva for two or more months, so that the large proportion of patients with early progression will never have been a candidate for more than an early amount of dose reduction.

我不认为高剂量会加快耐药的产生。相反，我认为有几个潜在因素。首先，许多EGFR突变的病人对特罗凯的正副作用非常敏感，对于这些人，需要减少剂量到25-50mg/d。我非常怀疑EGFR没有突变的人群会取得同样好的结果，前面所有相关报道都是基于EGFR突变的病人。
我并不认为在一个EGFR突变病人不占主要比例的人群中会取得类似的结果。
其次，它通常需要几个月的时间将剂量逐渐下降至25-50mg/d，所以我怀疑很多人降低剂量前已经服用特罗凯两月或更多月，所以服用较小剂量的人群中并没有多少进展期的病人。

不知高剂量或低剂量对耐药有没有显著的不同？

话说回来， 如果25mg真的效果很好的话，这个吃正版药还真的有可能呢。 我爸爸E21突变。期待讨论。

期待更详细的说明

如果作为维持性用药，体内无病灶，CEA又处低水平，又有基因突变，可能低剂量能行，即胜任维持作用；否则，必定无法控制住病情，其治疗的药浓度太低。

憨豆精神 发表于 2011-9-27 20:10

                               
登录/注册后可看大图

如果作为维持性用药，体内无病灶，CEA又处低水平，又有基因突变，可能低剂量能行，即胜任维持作用；否则，必 ...

憨叔，列的条件你完全符合啊。有计划一试吗？

这也是一种无奈的选择,支持!

以德服人 发表于 2011-9-27 21:25

                               
登录/注册后可看大图

憨叔，列的条件你完全符合啊。有计划一试吗？

因为我不吃正版的，所以减量对我来说没经济意义，我上次整个月就是减量吃，100毫克一天，副作用几乎没有了。

学习了。。。