吸烟患者加量使用特罗凯--高剂量能改进效果么

jimmy112199

本文介绍了35位吸烟患者的实验，吸烟者加倍剂量后生存时间从5.45月到9.56个月。

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

We have long noted that there is a clear association of smokinghistory with effectiveness of oral EGFR tyrosine kinase inhibitors(TKIs).   Part of this is because never-smokers have a high incidenceof carrying activating EGFR mutations, but also potentially becausecurrent 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 developlittle or no rash.  A recent study just coming out in the Journal ofClinical Oncology from a group in the UK has studied blood levels withdose escalation of  tarceva (erlotinib) among current smokers (abstract here)and suggests a possible value in giving higher than standard tarcevadosing among current smokers, so that they can achieve the same bloodlevels as never-smokers or former smokers.  Will this lead to betterresults for these patients?

    The clinical trial enrolled patientswho smoked at least 10 cigarettes per day and first escalated the doseof tarceva from 200 to 350 mg daily and carefully assessed sideeffects.  While the standard “maximum tolerated dose” with tarceva in ageneral population is 150 mg/day, this population of current smokersreached the level of frequent rash and diarrhea and fatigue at 300mg/day.  One thing this work demonstrated was that escalating the dosecould bring current smokers to the side effect severity and frequencymore typical of never-smokers or prior smokers.
    The trial then entered another phase that enrolled 35 currentsmokers to receive either the standard dose of 150 mg/day or 300mg/day.   Looking at the blood levels in patients, the higher dosetranslated to higher blood levels, which are comparable to the levelsof people who don’t smoke:
(click to enlarge)
    Interestingly, the patients who received the higher dose oftarceva had a median pverall survival of 9.56 months, compared with5.45 months for current smokers who received tarceva at 150 mg/day(pretty similar to the median overall survival of 6.1 months in thelarger BR.21 trial of tarceva vs. placebo (abstract here).
   However, we need to keep the results of this small trial inperspective.  This trial had just a few dozen patients, so comparisonof very small groups is only provocative, not conclusive at all.  Itsuggests that there is a value in asking the question of whetherescalating dose in current smokers might be benefcial.  But the BR.21trial didn’t show a better result in former smokers (median overallsurvival 5.5 months) than current smokers, and the former smokersshouldn’t be metabolizing tarceva faster and getting lower bloodlevels: interestingly, the package insert for tarceva says that doctorsmight consider giving a higher dose than the standard 150 mg to currentsmokers, but we just don’t have much evidence to guide us here.  And atabout $3500/month for tarceva at the standard dose, I can imagine manyinsurers balking at doubling that cost based on something that is amere hypothesis waiting to be tested more thoroughly.  But at least thelittle work done thus far suggests that we might improve outcomes forsmokers receiving tarceva by re-evaluating whether they’re receivingthe best dose right now.

roche

其实说到底，吸烟的患者是因为导致 药物的代谢比较快所以效果比不上不吸烟的。
从这个角度讲楼主的 观点是非常好理解的。

不过要注意 皮疹的发生