Geller James I, Wall Donna, Perentesis John, Blaney Susan M, Bernstein Mark
Department of Hematology-Oncology, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio 45229-3039, USA.
Pediatr Blood Cancer. 2009 Mar;52(3):346-50. doi: 10.1002/pbc.21820.
A dose-escalation Phase I study of taxol (paclitaxel) administered in combination with standard dose ifosfamide was conducted in children with relapsed or refractory solid tumors. Primary objectives were to estimate the maximum tolerated dose (MTD) and to describe the dose-limiting toxicities (DLTs).
Paclitaxel was administered as a 6-hr continuous infusion (hr 0-6), followed by intravenous ifosfamide (2 g/m(2)/day x 3 days) over 1 hr at hours 6-7, 24-25, and 48-49. Patients at dose level 1 received 250 mg/m(2) paclitaxel. Subsequent dose escalation proceeded using a standard 3 x 3 Phase I design.
Fifteen patients received a combined 46 courses of therapy. The median age was 14.5 years (range, 2-19 years), and diagnoses included sarcoma (7), neuroblastoma (3), and other (5). Three patients received paclitaxel at 250 mg/m(2) (10 courses), six at 325 mg/m(2) (19 courses), three at 425 mg/m(2) (8 courses), and three at 550 mg/m(2) (9 courses). DLTs occurred in 2/3 patients at 550 mg/m(2) paclitaxel during cycle 1, including grade 3 hypotension and grade 4 anaphylaxis in 1 patient each. Common non-dose-limiting toxicities included bone marrow suppression and peripheral neuropathy. Response was evaluable in 14 patients and included mixed response (3), stable disease (5), and progressive disease (6).
Paclitaxel hypersensitivity reactions were dose limiting when the drug was administered as a 6-hr infusion. The MTD and recommended Phase II dose of paclitaxel administered as a 6-hr continuous intravenous infusion followed by standard dose intravenous ifosfamide is 425 mg/m(2) paclitaxel.
对复发或难治性实体瘤患儿开展一项紫杉醇联合标准剂量异环磷酰胺的剂量递增Ⅰ期研究。主要目的是评估最大耐受剂量（MTD）并描述剂量限制性毒性（DLT）。
紫杉醇采用6小时持续输注（0至6小时），随后在第6至7小时、24至25小时和48至49小时静脉输注异环磷酰胺（2g/m²/天×3天），持续1小时。1级剂量组患者接受250mg/m²紫杉醇治疗。后续剂量递增采用标准的3×3Ⅰ期设计。
15例患者共接受了46个疗程的治疗。中位年龄为14.5岁（范围2至19岁），诊断包括肉瘤（7例）、神经母细胞瘤（3例）和其他（5例）。3例患者接受250mg/m²紫杉醇治疗（10个疗程），6例接受325mg/m²治疗（19个疗程），3例接受425mg/m²治疗（8个疗程），3例接受550mg/m²治疗（9个疗程）。在第1周期中，550mg/m²紫杉醇治疗的3例患者中有2例出现DLT，其中1例出现3级低血压，1例出现4级过敏反应。常见的非剂量限制性毒性包括骨髓抑制和周围神经病变。14例患者的疗效可评估，包括混合反应（3例）、疾病稳定（5例）和疾病进展（6例）。
当紫杉醇采用6小时输注给药时，过敏反应是剂量限制性的。紫杉醇采用6小时持续静脉输注随后给予标准剂量静脉异环磷酰胺的MTD和推荐Ⅱ期剂量为425mg/m²紫杉醇。
