易瑞沙可以吃两粒么？

gexiaom

3、加量服用并不能够提高有效率，之前我也在母亲耐药之后加量服用，确实没有见好转
http://photo.blog.sina.com.cn/bl ... 3bf4b15523bbadb6f60

噎死爱肚

吃2颗意义不大

jimmy112199

吸烟患者加倍服用后，血中有效成分含量与不吸烟患者正常剂量时相同，生存期延长，所以一些医生建议吸烟患者剂量加倍。见所附文献(文中实验用的是特罗凯)


Tarceva Dose Escalation in Current Smokers: Could Higher Doses Improve Results?

   We have long noted that there is a clear association of smoking history with effectiveness of oral EGFR tyrosine kinase inhibitors (TKIs).   Part of this is because never-smokers have a high incidence of carrying activating EGFR mutations, but also potentially because current smokers actually metabolize EGFR TKIs faster (see prior post).   We’ve seen a consistent association of rash development with better outcome (see prior post), and current smokers have been disproportionately likely to develop little or no rash.  A recent study just coming out in the Journal of Clinical Oncology from a group in the UK has studied blood levels with dose escalation of  tarceva (erlotinib) among current smokers (abstract here) and suggests a possible value in giving higher than standard tarceva dosing among current smokers, so that they can achieve the same blood levels as never-smokers or former smokers.  Will this lead to better results for these patients?

    The clinical trial enrolled patients who smoked at least 10 cigarettes per day and first escalated the dose of tarceva from 200 to 350 mg daily and carefully assessed side effects.  While the standard “maximum tolerated dose” with tarceva in a general population is 150 mg/day, this population of current smokers reached the level of frequent rash and diarrhea and fatigue at 300 mg/day.  One thing this work demonstrated was that escalating the dose could bring current smokers to the side effect severity and frequency more typical of never-smokers or prior smokers.

    The trial then entered another phase that enrolled 35 current smokers to receive either the standard dose of 150 mg/day or 300 mg/day.   Looking at the blood levels in patients, the higher dose translated to higher blood levels, which are comparable to the levels of people who don’t smoke:

erlotinib PK in Smokers (click to enlarge)

    Interestingly, the patients who received the higher dose of tarceva had a median pverall survival of 9.56 months, compared with 5.45 months for current smokers who received tarceva at 150 mg/day (pretty similar to the median overall survival of 6.1 months in the larger BR.21 trial of tarceva vs. placebo (abstract here).

   However, we need to keep the results of this small trial in perspective.  This trial had just a few dozen patients, so comparison of very small groups is only provocative, not conclusive at all.  It suggests that there is a value in asking the question of whether escalating dose in current smokers might be benefcial.  But the BR.21 trial didn’t show a better result in former smokers (median overall survival 5.5 months) than current smokers, and the former smokers shouldn’t be metabolizing tarceva faster and getting lower blood levels: interestingly, the package insert for tarceva says that doctors might consider giving a higher dose than the standard 150 mg to current smokers, but we just don’t have much evidence to guide us here.  And at about $3500/month for tarceva at the standard dose, I can imagine many insurers balking at doubling that cost based on something that is a mere hypothesis waiting to be tested more thoroughly.  But at least the little work done thus far suggests that we might improve outcomes for smokers receiving tarceva by re-evaluating whether they’re receiving the best dose right now.

[ 本帖最后由 jimmy112199 于 2009-3-26 07:24 编辑 ]

weiwuzi

上文的汉译，Google的，没校对字句，大家参考一下吧：
特罗凯剂量递增在目前的吸烟者：请问高剂量提高的结果？

   我们早就指出，有明显的吸烟史协会与效力的口头表皮生长因子受体酪氨酸激酶抑制剂（ TKIs ） 。这部分是因为从未吸烟者的发病率很高进行活化EGFR突变，但也可能是因为目前的吸烟者实际代谢表皮生长因子受体TKIs更快（见事先后） 。我们看到了一致协会皮疹发展有更好的结果（见事先后） ，和目前的吸烟者已不成比例可能很少或没有发展皮疹。最近的一项研究刚刚在临床肿瘤学杂志从一组在英国的研究水平与剂量血升级特罗凯（埃罗替尼）在目前的吸烟者（摘要这里） ，并建议一个可能的值给予高于标准剂量之间特罗凯目前的吸烟者，使他们能够达到同样的血液从未吸烟或戒烟。这将导致更好的结果，这些患者？

    临床试验注册谁吸烟患者至少有10支香烟每天第一个升级的剂量特罗凯由200至350毫克每日和仔细评估副作用。虽然标准的“最大耐受剂量”与特罗凯在总人口为150毫克/天，这一人口目前吸烟者的水平达成频繁皮疹和腹泻和疲劳在300毫克/天。有一件事表明这项工作是不断升级的剂量可以使吸烟者的副作用的严重性和频率较典型的从未吸烟或事先吸烟者。

    审判后，进入另一阶段，目前招收35名吸烟者，接受标准剂量为150毫克/天或300毫克/天。看着患者血液中的高剂量翻译血液水平较高，其中具有可比性的水平的人谁不吸烟：

埃罗替尼的PK在吸烟者（点击放大）

    有趣的是，患者谁获得较高剂量的特罗凯进行了中间pverall生存九点五六个月，与之相比五点四五个月目前吸烟者谁收到特罗凯在150毫克/天（非常相似总存活时间中位数6.1个月，较大的巴0.21审判特罗凯安慰剂（摘要这里） 。

   然而，我们需要不断的结果，这个小审判中的观点。这项试验已仅有数十位患者，因此比较非常小的群体只有挑衅性的，不是决定性的。这表明，有一个价值的要求的问题是，是否升级剂量在目前的吸烟者可能benefcial 。但BR.21审判没有表现出更好的结果的前吸烟者（中位生存5.5个月）比目前的吸烟者和前吸烟者不应代谢速度更快，让特罗凯降低血压水平：有趣的是，说明书的特罗凯说，医生可能会考虑给予高剂量超过150毫克的标准，以目前的吸烟者，但我们没有足够的证据来指导我们这里。和约3500/month的特罗凯的标准剂量，我可以想像许多保险公司不愿意增加一倍，成本基础上的东西只是一个假设等待更彻底的测试。但至少一点迄今所做的工作表明，现在我们可以改善的结果吸烟者接受特罗凯的重新评估它们是否会收到最好的剂量。

[ 本帖最后由 weiwuzi 于 2009-3-26 10:30 编辑 ]