酪丝亮肽注射液Ⅰ期临床耐受性研究

A phase I trial for evaluating the tolerance of tyroserleutide

目的：评价抗癌新药酪丝亮肽的人体安全性,确定推荐Ⅱ期临床研究的剂量。方法：分为连续3 d和30 d给药两部分。共入选21例健康受试者和18例恶性肿瘤患者,每剂量组3例,3 d给药试验共设7个剂量组（0.15,0.3,0.6,1.2,2.4,3.6,4.8 mg.m-2.d-1）,连续静脉给药3 d;30 d给药试验共设6个剂量组（0.3,0.6,1.2,2.4,3.6,4.8 mg·m^-2·d^-1）,连续静脉给药30 d。结果：21例健康受试者和18例恶性肿瘤患者连续给药均无不良事件发生,没有出现剂量限制性毒性。未观察到骨髓抑制、肝肾功能损害、消化道及心血管系统毒性。结论：酪丝亮肽无明显毒副作用,人体耐受性好。推荐Ⅱ期临床使用剂量及方法为：酪丝亮肽注射液1.2-2.4 mg·m^-2·d^-1,静脉给药,连用30 d。

Objective ：To evaluate the safety and maximum tolerated dose （MTD） of tyroserleutide, a new anticancer drug, in healthy volunteers and cancer patients. Methods： Twenty-one healthy volunteers and 18 cancer patients were intravenously infused with tyroserleutide for 3 or 30 d. Tyroserleutide was given for 3 d （0.15, 0.3, 0.6, 1.2, 2.4, 3.6, 4.8mg·m^-2·d^-1）, orfor30d （0.3, 0.6, 1.2, 2.4, 3.6, 4.8mg·m^-2·d^-1）. Results： No major adverse reactions and dose-limited toxicity were observed in 21 volunteers and 18 cancer patients. The bone marrow depression, functional impairments of the liver and kidney, toxic reactions in digestive and cardiovascular systems were not found. Conclusion ： The toxicity of tyroserleutide is mild, and subjects can be well tolerated. The recommended dose regimen for phase II trial is 1.2 -2.4 mg·m^-2·d^-1 , intravenous infusion, once daily for 30 d.