Ettinger L J, Krailo M D, Gaynon P S, Hammond G D
Department of Pediatrics, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, New Brunswick.
Cancer. 1993 Aug 1;72(3):917-22. doi: 10.1002/1097-0142(19930801)72:3<917::aid-cncr2820720342>3.0.co;2-q.
Carboplatin is an analogue of cisplatin with less nonhematologic toxicity and a similar spectrum of antineoplastic activity as the parent compound. Although cisplatin has not been found to be an active agent in leukemia, carboplatin induced complete remissions in adults with acute myelogenous leukemia (AML). Therefore, a pediatric Phase I study in acute leukemia was performed.
Between January 1988 and April 1990, the Childrens Cancer Group performed a Phase I study of carboplatin administered by a 5-day continuous intravenous infusion to children with acute leukemia in bone marrow relapse.
Mild to moderate glomerular and tubular nephrotoxicity was seen in most patients treated at the initial dose level of 336 mg/m2/day. Therefore, patients at the second dose level were treated at 270 mg/m2/day. At this level, one patient died of acute hepatic necrosis and hepatic encephalopathy, and a second patient had presumed hemorrhagic cystitis develop. The third dose level tested, 216 mg/m2/day, was not associated with unacceptable toxic effects and was considered the maximum tolerated dose (dose-limiting toxicity was not observed). Within the confines of this Phase I study, antileukemic activity was shown in patients with acute lymphoblastic leukemia (ALL) and AML.
In this pediatric Phase I trial of carboplatin in acute leukemia, glomerular and tubular nephrotoxicity was considered dose-limiting. In addition, hepatotoxicity and hemorrhagic cystitis were observed. Antileukemic activity was shown in patients with ALL and AML. The recommended Phase II dose is 216 mg/m2/day by 5-day continuous intravenous infusion.
卡铂是顺铂的类似物，非血液学毒性较小，抗肿瘤活性谱与母体化合物相似。虽然顺铂在白血病中未被发现是一种活性药物，但卡铂可使成人急性髓性白血病（AML）患者达到完全缓解。因此，开展了一项针对急性白血病的儿科I期研究。
1988年1月至1990年4月期间，儿童癌症研究组对骨髓复发的急性白血病患儿进行了一项卡铂的I期研究，采用为期5天的持续静脉输注给药。
在初始剂量水平336mg/m²/天治疗的大多数患者中观察到轻至中度的肾小球和肾小管肾毒性。因此，第二剂量水平的患者以270mg/m²/天进行治疗。在此剂量水平下，一名患者死于急性肝坏死和肝性脑病，另一名患者出现疑似出血性膀胱炎。所测试的第三剂量水平为216mg/m²/天，未出现不可接受的毒性作用，被认为是最大耐受剂量（未观察到剂量限制性毒性）。在本I期研究范围内，急性淋巴细胞白血病（ALL）和AML患者显示出抗白血病活性。
在这项卡铂用于急性白血病的儿科I期试验中，肾小球和肾小管肾毒性被认为是剂量限制性的。此外，还观察到肝毒性和出血性膀胱炎。ALL和AML患者显示出抗白血病活性。推荐的II期剂量为216mg/m²/天，通过为期5天的持续静脉输注给药。
