Holcenberg J S, Tutsch K D, Earhart R H, Ungerleider R S, Kamen B A, Pratt C B, Gribble T J, Glaubiger D L
Cancer Treat Rep. 1986 Jun;70(6):703-9.
A phase I study of ICRF-187 as a 2-hour iv infusion daily for 3 days was conducted in 46 evaluable pediatric patients. The maximum tolerated dose was 3500 mg/m2/day X 3 based on changes in hepatic function and coagulation abnormalities encountered when larger dosages were administered. One patient with acute lymphocytic leukemia achieved a complete remission and four cleared the blood of lymphoblasts. No other objective responses were seen. Pharmacokinetic analysis showed that the children had a larger volume of distribution per kilogram of body weight in the central compartment and total body and a more rapid total-body clearance than adults. These parameters can explain only part of the increased tolerance of children to ICRF-187.
对46名可评估的儿科患者进行了一项关于ICRF - 187的I期研究，静脉输注2小时，每天1次，共3天。基于给予较大剂量时出现的肝功能变化和凝血异常，最大耐受剂量为3500 mg/m²/天×3天。一名急性淋巴细胞白血病患者实现了完全缓解，四名患者清除了血液中的淋巴母细胞。未观察到其他客观反应。药代动力学分析表明，儿童每千克体重在中央室和全身的分布容积比成人更大，全身清除率也比成人更快。这些参数只能部分解释儿童对ICRF - 187耐受性增加的原因。
