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[目的]探讨靶向性、非细胞毒抗肿瘤药物的临床试验设计。[方法]本文总结了80项国内外近年开展的靶向性、非细胞毒药物的Ⅰ期临床试验,对每一项试验,我们分别从出入组标准、起始剂量的确定、爬升剂量的方法和最终确定Ⅱ期推荐剂量的方法等几方面进行分析。[结果]80项临床试验中,有48项以毒性反应作为停止剂量爬升的主要原因,8项以药代动力学试验结果为依据,与推荐Ⅱ期剂量的结果相一致。非传统的检测手段,如靶点效应的评价、影像学评价等均未常规在方案中设计,或很少在推荐Ⅱ期剂量时使用。[结论]到目前为止,靶向性、非细胞毒抗肿瘤药物Ⅰ期试验仍沿用“毒性”和药代动力学指标作为观察终点。如何更有效的评价此类药物的分子靶点效应,在早期的临床试验中筛选出有效药物值得在今后进一步研究。
[Objective] To explore the clinical trial design of targeted, non-cytotoxic anticancer drugs. [Method] This paper summarizes 80 phase Ⅰ clinical trials of targeted and non-cytotoxic drugs in recent years at home and abroad. For each experiment, we separately from the standard of access group, the determination of initial dose, the method of climbing dose And finally determine the recommended dose of Ⅱ methods such as several aspects of analysis. [Results] Among the 80 clinical trials, 48 were the main reasons for the toxic reaction to climb as the stopping dose. Eight items were based on the results of pharmacokinetic test and were consistent with the results of the recommended phase Ⅱ dose. Non-traditional means of detection, such as the evaluation of the target effect, imaging evaluation are not routinely designed in the program, or rarely used in the recommended dose. [Conclusion] So far, the first phase of targeted, non-cytotoxic antitumor drugs still follow the “toxicity” and pharmacokinetic parameters as the end point. How to more effectively evaluate the molecular target effect of these drugs, screening out effective drugs in early clinical trials is worth further study in the future.