Bomgaars L, Kerr J, Berg S, Kuttesch J, Klenke R, Blaney S M
Texas Children's Cancer Center/Baylor College of Medicine, Houston, TX 77030, USA.
Pediatr Blood Cancer. 2006 Jan;46(1):50-5. doi: 10.1002/pbc.20355.
The objectives of this study were to determine the maximum tolerated dose (MTD), dose-limiting toxicities (DLTs), pharmacokinetics, and anti-tumor effect of irinotecan in pediatric patients with recurrent or refractory malignancies.
Twenty-three patients between 1 and 21 years of age, with a solid tumor refractory to standard therapy or for which there was no standard therapy were enrolled. Irinotecan was administered over 90 min weekly 4x, every 6 weeks. The initial dose level was 125 mg/m(2)/day, with subsequent escalations to 160 and 200 mg/m(2)/day. A MTD was defined in heavily-pretreated and less-heavily-pretreated (< or =2 prior chemotherapy regimens, no prior bone marrow transplantation, and no central axis radiation) patients. Pharmacokinetic studies were also performed.
Neutropenia and diarrhea were the DLTs in heavily pretreated patients; the MTD was 125 mg/m(2)/day. Neutropenia was the DLT in less-heavily pretreated; the MTD was 160 mg/m(2)/day. Five patients had stable disease for two to four cycles including one patient each with rhabdomyosarcoma, Ewing sarcoma, neuroblastoma, and two patients with ependymoma. Irinotecan clearance was greater that that previously reported for children receiving high dose irinotecan.
The recommended phase II dose of irinotecan administered weekly 4x, every 6 weeks in children with solid tumors is 125 mg/m(2)/dose for heavily pretreated patients and 160 mg/m(2)/dose for less heavily pretreated patients.
本研究的目的是确定伊立替康在复发或难治性恶性肿瘤儿科患者中的最大耐受剂量（MTD）、剂量限制性毒性（DLT）、药代动力学和抗肿瘤效果。
纳入23例年龄在1至21岁之间、患有对标准治疗难治或无标准治疗的实体瘤患者。伊立替康每6周每周给药1次，共4次，持续90分钟。初始剂量水平为125mg/m²/天，随后逐步增至160和200mg/m²/天。在预处理较重和预处理较轻（≤2个先前化疗方案、无先前骨髓移植且无中枢轴放疗）的患者中确定MTD。还进行了药代动力学研究。
预处理较重的患者中，中性粒细胞减少和腹泻是DLT；MTD为125mg/m²/天。预处理较轻的患者中，中性粒细胞减少是DLT；MTD为160mg/m²/天。5例患者病情稳定2至4个周期，其中横纹肌肉瘤、尤因肉瘤、神经母细胞瘤各1例，室管膜瘤2例。伊立替康清除率高于先前报道的接受高剂量伊立替康的儿童。
对于实体瘤儿童患者，每6周每周给药1次、共4次的伊立替康推荐II期剂量，预处理较重的患者为125mg/m²/剂量，预处理较轻的患者为160mg/m²/剂量。
