Blaney S, Berg S L, Pratt C, Weitman S, Sullivan J, Luchtman-Jones L, Bernstein M
Texas Children's Cancer Center/Baylor College of Medicine, Houston 77030, USA.
Clin Cancer Res. 2001 Jan;7(1):32-7.
A Phase I trial of irinotecan was performed to determine the maximum tolerated dose (MTD), the dose-limiting toxicities (DLTs), and the incidence and severity of other toxicities in children with refractory solid tumors. Thirty-five children received 146 courses of irinotecan administered as a 60-min i.v. infusion, daily for 5 days, every 21 days, after premedication with dexamethasone and ondansetron. Doses ranged from 30 mg/m2 to 65 mg/m2. An MTD was defined in heavily pretreated and less-heavily pretreated (i.e., two prior chemotherapy regimens, no prior bone marrow transplantation, and no radiation to the spine, skull, ribs, or pelvic bones) patients. Myelosuppression was the primary DLT in heavily pretreated patients, and diarrhea was the DLT in less-heavily pretreated patients. The MTD in the heavily pretreated patient group was 39 mg/m2, and the MTD in the less-heavily pretreated patients was 50 mg/m2. Non-dose-limiting diarrhea that was well controlled and of brief duration was observed in approximately 75% of patients. A partial response was observed in one patient with neuroblastoma, and in one patient with hepatocellular carcinoma. Stable disease (4-20 cycles) was observed in seven patients with a variety of malignancies including neuroblastoma, pineoblastoma, glioblastoma, brainstem glioma, osteosarcoma, hepatoblastoma, and a central nervous system rhabdoid tumor. In conclusion, the recommended Phase II dose of irinotecan administered as a 60-min i.v. infusion daily for 5 days, every 21 days, is 39 mg/m2 in heavily treated and 50 mg/m2 in less-heavily treated children with solid tumors.
进行了一项伊立替康的I期试验，以确定难治性实体瘤患儿的最大耐受剂量（MTD）、剂量限制性毒性（DLT）以及其他毒性的发生率和严重程度。35名儿童接受了146个疗程的伊立替康治疗，通过静脉输注60分钟，每天1次，共5天，每21天重复一次，用药前给予地塞米松和昂丹司琼预处理。剂量范围为30mg/m²至65mg/m²。在预处理程度高和预处理程度低（即接受过两种先前化疗方案、未接受过骨髓移植且未接受过脊柱、颅骨、肋骨或骨盆放疗）的患者中定义了MTD。预处理程度高的患者中，骨髓抑制是主要的DLT，而预处理程度低的患者中，腹泻是DLT。预处理程度高的患者组的MTD为39mg/m²，预处理程度低的患者的MTD为50mg/m²。约75%的患者出现了可良好控制且持续时间短的非剂量限制性腹泻。1例神经母细胞瘤患者和1例肝细胞癌患者出现部分缓解。7例患有多种恶性肿瘤（包括神经母细胞瘤、松果体母细胞瘤、胶质母细胞瘤、脑干胶质瘤、骨肉瘤、肝母细胞瘤和中枢神经系统横纹肌样瘤）的患者病情稳定（4 - 20个周期）。总之，对于难治性实体瘤患儿，推荐的伊立替康II期剂量为静脉输注60分钟，每天1次，共5天，每21天重复，预处理程度高的患儿为39mg/m²，预处理程度低的患儿为50mg/m²。
