近日，Journal of Clinical Oncology发表的一项对用于药品注册的随机对照试验的分析结果显示，很多新的抗癌药物都是有代价的——包括更高风险的腹泻、皮疹和高血压。加拿大研究人员分析了FDA在2000年到2010年批准的38种抗癌药物，包括治疗结肠癌、乳腺癌和肺癌的药物。研究表明，这些新的抗癌药物相比于老药造成更加明显的副作用，更多治疗相关的死亡。
未参与这项研究的Susan Ellenberg博士讲到，人们在用药时要综合考虑疗效和毒性，当人们认为药物可以增加癌症治愈的机会，他们愿意接受一定程度的过量毒性，但是这也不总是正确，真正取决于毒性是什么。
这些被调查的药物包括贝伐珠单抗、多西他赛和舒尼替尼。每个研究的人数均是在266和1725名癌症患者之间。研究人员发现，被随机分配到新药物组的癌症病人比对照组（目前的标准治疗或安慰剂）死于不良反应的可能性高40%。然而，总共来讲，不到1%的人发生治疗相关的死亡，因为副作用停药的人数为不到1%到7%。
新药物治疗组的病人，有52%更多的可能性发生严重至可能的威胁生命的不良反应，从神经损伤到心脏问题。
总的来说，从临床试验数据看来，病人获益要超过风险，但是现实世界中患者是复杂的，他们有各种各样的问题，因此，利益和风险可能会有所不同。当病人和医生开始一个新的治疗时，医生要改考虑病人的整体健康，而不仅仅是癌症。（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.
