A phase I study of irinotecan as a 3-week schedule in children with refractory or recurrent solid tumors
A phase I study of irinotecan as a 3-week schedule in children with refractory or recurrent solid tumors
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DOI：
10.1200/jco.2003.08.175
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发表时间：
2003-10-15
影响因子：
45.3
通讯作者：
Pein, F
中科院分区：
文献类型：
--
作者：
Vassal, G;Doz, F;Pein, F
目的：进行了一项1期研究，以确定伊立替康（CPT-11）每3周单次静脉输注用于复发或难治性实体瘤儿童的最大耐受剂量（MTD）和安全性。患者和方法：纳入81例患者，包括48例轻度预处理患者和33例重度预处理患者（颅脑照射和/或高剂量化疗）。儿童接受CPT-11输液120分钟，剂量范围为200至720mg /m(2)。测定两组患者第一周期的剂量限制性毒性（DLT）。结果：轻度预处理组122个周期，重度预处理组81个周期。原发DLT为预处理程度较低患者的延迟性腹泻，预处理程度较高患者的中性粒细胞减少。两组患者的MTD均为600 mg/m(2)。3 - 4级中性粒细胞减少症分别发生在33%和38%的治疗周期中。3 - 4级非血液学毒性包括恶心/呕吐（轻度和重度预处理患者分别占周期的7%和4%）、虚弱（分别占周期的7%和4%）和延迟性腹泻（分别占周期的6%和2.5%）。在600 Mg/m(2)的剂量下，观察到4个部分反应（高级别胶质瘤、神经母细胞瘤、髓母细胞瘤和横纹肌肉瘤）和21个轻微反应和稳定的疾病。对77例患者进行CPT-11和SN-38的药代动力学分析。平均+/-标准差（SD） CPT- 11血浆清除率为20.7 +/- 9.5 L/h/m(2)（范围5至54）。SD -38代谢率平均值为1.5% +/- 1.1%（范围0.15% ~ 5.55%）。结论：在轻度和重度预处理的实体瘤儿童中，推荐的11期剂量为600 mg/m(2)。(C) 2003年由美国临床肿瘤学会出版。
Purpose: A phase 1 study was performed to determine the maximum-tolerated dose (MTD) and safety profile of irinotecan (CPT-11) administered as a single intravenous infusion every 3 weeks in children with recurrent or refractory solid tumors.Patients and Methods: Eighty-one patients were enrolled, including 48 less heavily, and 33 heavily pretreated patients (cranial irradiation and/or high-dose chemotherapy). Children received CPT-11 as a 120-minute infusion at doses ranging from 200 to 720 mg/m(2). The dose-limiting toxicities (DLT) on first cycle were determined in both cohorts.Results: One hundred twenty-two cycles and 81 cycles were administered in less heavily, and heavily pretreated patients, respectively. The primary DLT was delayed diarrhea in less heavily pretreated patients, and neutropenia in heavily pretreated patients. MTD was 600 mg/m(2) in both cohorts. Grade 3 to 4 neutropenia occurred in 33% and 38% of cycles in less heavily, and heavily pretreated patients, respectively. Grade 3 to 4 nonhematologic toxicities included nausea/vomiting (7% and 4% of cycles in less heavily, and heavily pretreated patients, respectively), asthenia (7% and 4% of cycles, respectively), and delayed diarrhea (6% and 2.5% of cycles, respectively). Four partial responses at 600 Mg/m(2) (high-grade glioma, neuroblastoma, medulloblastoma, and rhabdomyosarcoma) and 21 minor responses and stable diseases were observed. Pharmacokinetic analysis of CPT-11 and SN-38 was performed in 77 patients. The mean +/- standard deviation (SD) CPT- 11 plasma clearance was 20.7 +/- 9.5 L/h/m(2) (range, 5 to 54). The mean SD SN-38 metabolic ratio was 1.5% +/- 1.1% (range, 0.15% to 5.55%).Conclusion: The recommended phase 11 dose of CPT-11 in a 3-week schedule is 600 mg/m(2) in less heavily, and heavily pretreated children with solid tumors. (C) 2003 by American Society of Clinical Oncology.