Inaba M
Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Tokyo.
Gan To Kagaku Ryoho. 1991 Jul;18(9):1449-56.
Clinical predictability of preclinical test for antitumor agents has not been significantly improved even after the use of a human tumor/nude mouse model. Such different antitumor activities between preclinical and clinical tests probably due to the fact that therapeutic used in both tests usually each maximum tolerated dose (MTD), are pharmacokinetically not equivalent. Therefore, we introduced a new concept of "clinically equivalent dose (CED)", which can reproduce in the nude mouse the blood level of a given drug observed with human patients received its therapeutic dose. Treatment of human tumors implanted in the nude mice with CEDs of several drugs exhibited much better correlation with their clinical efficacies than those with MTDs. The feasibility of use of CED predicted by animal scale-up procedure as a therapeutic dose in the preclinical test was discussed.
即使使用了人肿瘤/裸鼠模型，抗肿瘤药物临床前试验的临床可预测性仍未得到显著改善。临床前试验和临床试验之间如此不同的抗肿瘤活性可能是由于这两种试验中使用的治疗方法通常都是各自的最大耐受剂量（MTD），在药代动力学上并不等效。因此，我们引入了“临床等效剂量（CED）”这一新概念，它可以在裸鼠中重现接受治疗剂量的人类患者所观察到的给定药物的血药浓度。用几种药物的CED治疗植入裸鼠的人肿瘤，与用MTD治疗相比，其与临床疗效的相关性要好得多。讨论了将动物放大程序预测的CED用作临床前试验治疗剂量的可行性。
