Institut Gustave Roussy, Department of Paediatric and Adolescent Medicine, University Paris-Sud, Villejuif, France.
Eur J Cancer. 2012 Jan;48(2):253-62. doi: 10.1016/j.ejca.2011.09.021. Epub 2011 Oct 25.
A phase II study of temsirolimus was conducted in children and adolescents with high-grade glioma, neuroblastoma or rhabdomyosarcoma.
Temsirolimus 75 mg/m(2) was administered once weekly until disease progression or intolerance. Using the Simon 2-stage design, further enrolment in each disease cohort required ≥ 2 objective responses within the first 12 weeks for the first 12 evaluable patients (those who received ≥ 3 temsirolimus doses).
Fifty-two heavily pretreated patients with relapsed (12%) or refractory (88%) disease, median age 8 years (range 1-21 years), were enroled and treated. One patient with neuroblastoma achieved confirmed partial response within the first 12 weeks; thus, none of the 3 cohorts met the criterion for continued enrolment. Disease stabilisation at week 12 was observed in 7 of 17 patients (41%) with high-grade glioma (5 diffuse pontine gliomas, 1 glioblastoma multiforme and 1 anaplastic astrocytoma), 6 of 19 (32%) with neuroblastoma and 1 of 16 (6%) with rhabdomyosarcoma (partial response confirmed at week 18). In the three cohorts, median duration of stable disease or better was 128, 663 and 75 d, respectively. The most common treatment-related adverse events were thrombocytopaenia, hyperlipidaemia and aesthenia. Pharmacokinetic findings were similar to those observed in adults.
Temsirolimus administered weekly at the dose of 75 mg/m(2) did not meet the primary objective efficacy threshold in children with high-grade glioma, neuroblastoma or rhabdomyosarcoma; however, meaningful prolonged stable disease merits further evaluation in combination therapy.
在患有高级别神经胶质瘤、神经母细胞瘤或横纹肌肉瘤的儿童和青少年中进行了西罗莫司的 II 期研究。
每周给予西罗莫司 75mg/m2，直到疾病进展或不耐受。采用 Simon 2 期设计，对于前 12 名可评估患者（接受了≥3 剂西罗莫司治疗的患者）中，在前 12 周内有≥2 例客观缓解，每个疾病队列进一步入组需要≥2 例客观缓解。
52 名患有复发性（12%）或难治性（88%）疾病的重度预处理患者，中位年龄为 8 岁（范围 1-21 岁），入组并接受治疗。1 名神经母细胞瘤患者在前 12 周内达到确认的部分缓解；因此，没有任何一个队列达到继续入组的标准。17 名高级别神经胶质瘤患者中有 7 名（41%）在第 12 周时疾病稳定，5 名弥漫性脑桥神经胶质瘤，1 名胶质母细胞瘤多形性和 1 名间变性星形细胞瘤；19 名神经母细胞瘤患者中有 6 名（32%）和 16 名横纹肌肉瘤患者中有 1 名（6%）在第 18 周时疾病稳定（确认部分缓解）。在这三个队列中，中位稳定疾病或更好的持续时间分别为 128、663 和 75d。最常见的与治疗相关的不良事件是血小板减少症、高脂血症和乏力。药代动力学发现与在成人中观察到的相似。
每周给予 75mg/m2 的西罗莫司剂量在患有高级别神经胶质瘤、神经母细胞瘤或横纹肌肉瘤的儿童中未达到主要疗效终点；然而，有意义的延长稳定疾病值得进一步评估联合治疗。
