Ann Oncol：揭示临床试验中副作用极小的新型靶向药物疗法

近日，一项刊登在国际杂志Annals of Oncology上的一篇研究报告中，来自伦敦癌症研究中心的研究小组揭示，癌症治疗中接受早期新药临床试验的病人相比传统的化疗表现出较低的副作用风险。文章中，研究者分析了36个一期临床试验的相关数据，发现接受新型药物治疗的病人比传统化疗病人患病风险降低了7倍多。

近日的研究成果发现接受新一代抗癌药物的病人，其应答率比接受老药物提高了2倍多，但是截至到现在，接受新药物所带来的风险却不得而知。因此，研究者开展了这项副作用风险研究。传统理论上的抗癌药物只是针对癌细胞发挥作用，对病人的副作用极小，当然这只是我们希望的样子，研究者的研究在临床I期研究中支持了癌症新药的这种理想化的情况。

更重要的是，研究者评估了病人接受高风险毒性所引发的效应，这将帮助医生制定更好的计划，来规划在什么时候用什么药物最合适。

研究者在2005年1月至2009年12月分析了687个病人的一些数据，这些病人患有各种类型的癌症包括胃肠道、妇科等。当然对于靶向药物而言，其最大的毒性就是给胃肠道带来的毒性，包括引发食欲缺失、痢疾等。如果给予病人高剂量的药物，病人往往会引发副作用，因此，研究者的新型靶向疗法是治疗癌症革命性的突破，也是治疗癌症的关键。

编译自：Lower Risk of Serious Side-Effects in Trials of New Targeted Drugs, Study Suggests

doi:10.1093/annonc/mds030
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Defining the risk of toxicity in phase I oncology trials of novel molecularly targeted agents: a single centre experience

L. R. Molife*, S. Alam, D. Olmos, M. Puglisi, K. Shah, R. Fehrmann, L. Trani, A. Tjokrowidjaja, J. S. de Bono, U. Banerji and S. B. Kaye

Background This study defined the risk of serious toxicity in phase I trials of molecularly targeted agents (MTA). Patients and methods A retrospective analysis of toxicity data from patients treated in phase I trials of MTAs was carried out to define the rate of treatment-related grade 3/4 toxic effects, deaths and risk factors associated with grade 3 or more toxicity. Results Data from 687 patients [median age, 59.1 years (range 12.5–85.5)] treated in 36 trials were analysed. Two hundred and eleven patients were of Eastern Cooperative Oncology Group performance status (PS) zero, 432 of PS one, 38 of PS two and 6 unknown. The rate of grade 3 and 4 events was 14.1% (n = 97) and 1.9% (n = 13), respectively. Twenty-four percent of events were gastrointestinal, 22% constitutional and 20% metabolic. PS two was associated with a higher risk of toxicity [odds ratio (OR), 2.6; 95% confidence interval (CI) 1.1–6.1; P = 0.032] as was receiving >100% of maximum tolerated dose or maximum administered dose (OR 2.5; CI 1.6–3.9; P < 0.001). Mortality rate was 0.43% (n = 3). Conclusions Therapy with novel MTAs in phase I trials is associated with a moderate risk of significant toxicity. This appears less than in phase I studies involving cytotoxic agents, particularly in relation to grade 4 toxicity. The risk of death is low.