近日，Journal of Clinical Oncology發(fā)表的一項(xiàng)對(duì)用于藥品注冊(cè)的隨機(jī)對(duì)照試驗(yàn)的分析結(jié)果顯示,，很多新的抗癌藥物都是有代價(jià)的——包括更高風(fēng)險(xiǎn)的腹瀉,、皮疹和高血壓。加拿大研究人員分析了FDA在2000年到2010年批準(zhǔn)的38種抗癌藥物,，包括治療結(jié)腸癌,、乳腺癌和肺癌的藥物。研究表明,，這些新的抗癌藥物相比于老藥造成更加明顯的副作用,，更多治療相關(guān)的死亡。
未參與這項(xiàng)研究的Susan Ellenberg博士講到,，人們?cè)谟盟帟r(shí)要綜合考慮療效和毒性,，當(dāng)人們認(rèn)為藥物可以增加癌癥治愈的機(jī)會(huì)，他們?cè)敢饨邮芤欢ǔ潭鹊倪^(guò)量毒性,，但是這也不總是正確,，真正取決于毒性是什么。
這些被調(diào)查的藥物包括貝伐珠單抗,、多西他賽和舒尼替尼,。每個(gè)研究的人數(shù)均是在266和1725名癌癥患者之間。研究人員發(fā)現(xiàn),，被隨機(jī)分配到新藥物組的癌癥病人比對(duì)照組（目前的標(biāo)準(zhǔn)治療或安慰劑）死于不良反應(yīng)的可能性高40%,。然而，總共來(lái)講,，不到1%的人發(fā)生治療相關(guān)的死亡,，因?yàn)楦弊饔猛Ｋ幍娜藬?shù)為不到1%到7%。
新藥物治療組的病人，有52%更多的可能性發(fā)生嚴(yán)重至可能的威脅生命的不良反應(yīng),，從神經(jīng)損傷到心臟問(wèn)題,。
總的來(lái)說(shuō)，從臨床試驗(yàn)數(shù)據(jù)看來(lái),，病人獲益要超過(guò)風(fēng)險(xiǎn),，但是現(xiàn)實(shí)世界中患者是復(fù)雜的，他們有各種各樣的問(wèn)題,，因此,，利益和風(fēng)險(xiǎn)可能會(huì)有所不同。當(dāng)病人和醫(yī)生開(kāi)始一個(gè)新的治療時(shí),，醫(yī)生要改考慮病人的整體健康,，而不僅僅是癌癥。（生物谷Bioon.com）
doi:10.1200/JCO.2011.40.3824
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The Price We Pay for Progress: A Meta-Analysis of Harms of Newly Approved Anticancer Drugs
Saroj Niraula, Bostjan Seruga, Alberto Ocana, Tiffany Shao, Robyn Goldstein, Ian F. Tannock and Eitan Amir?
Purpose Registration of new anticancer drugs is usually based on results of randomized controlled trials (RCTs) showing improved efficacy when compared with standard therapy. There is relatively less emphasis on toxicity. In our study, we analyze serious toxicities of newly approved anticancer drugs reported in pivotal RCTs used for drug registration.
Patients And methods We identified RCTs evaluating agents for the treatment of solid tumors approved by the US Food and Drug Administration between 2000 and 2010. Odds ratios (OR) and 95% CI were computed for three end points of safety and tolerability: treatment-related death, treatment-discontinuation related to toxicity, and grade 3 or 4 adverse events (AEs). These were then pooled in a meta-analysis. Correlations between these end points and the hazard ratios for overall survival (OS) and progression-free survival (PFS) were also assessed.
Results Thirty-eight RCTs were analyzed. Compared with control groups, the odds of toxic death was greater for new agents (OR, 1.40; 95% CI, 1.15 to 1.70; P < .001) as were the odds of treatment-discontinuation (OR, 1.33; 95% CI, 1.22 to 1.45, P < .001). Grade 3 or 4 AEs (OR, 1.52; 95% CI, 1.35 to 1. 71; P < .001) were also more common with new agents, especially nonhematologic AEs such as diarrhea, skin reactions, and neuropathy. There were no significant correlations between safety end points and OS or PFS.
Conclusion New anticancer agents that lead to improvements in time-to-event end points also increase morbidity and treatment-related mortality. The balance between efficacy and toxicity may be less favorable in clinical practice because of selection of fewer patients with good performance status and limited comorbidities. Patients' baseline health characteristics should be considered when choosing therapy.
