Department of Oncology, Birmingham Children's Hospital, Birmingham, UK.
Pediatr Blood Cancer. 2014 Mar;61(3):442-5. doi: 10.1002/pbc.24767. Epub 2013 Sep 9.
The prognosis for patients with nonpulmonary metastatic Ewing sarcoma remains poor with survival in the order of 15-20%. The need to introduce effective new agents into clinical practice is clear. Based on a preclinical rationale of responses in xenografts and backed by a phase I study in children, the Euro-E.W.I.N.G consortium planned a phase II window study of irinotecan in newly diagnosed high risk metastatic patients with Ewing sarcoma.
Patients were recruited between April 2004 and December 2007. Two courses of irinotecan were administered at a dose of 600 mg/m(2) as a 1 hour infusion at 21 day intervals. Response evaluation was determined after the second course of treatment by radiological assessment of primary and metastatic sites and, where appropriate bone marrow sampling.
Twenty-three patients were recruited. Two patients were deemed inevaluable for response. Five patients (24%) demonstrated a partial response. Grade 3 or 4 diarrhoea was seen in 4/43 course of treatment and was managed with loperamide.
This is the first report of single agent irinotecan activity in an untreated population of patients with Ewing sarcoma. In common with other paediatric tumours and other camptothecin analogues such as topotecan, single agent activity is only modest. The exact role for the use of irinotecan in patients with ES, dose schedule and combinations with other agents still requires further investigation.
非肺部转移性尤文肉瘤患者的预后仍然很差，生存率为 15-20%左右。显然，需要引入有效的新药进入临床实践。基于在异种移植物中的反应的临床前原理，并得到儿童阶段 I 研究的支持，Euro-E.W.I.N.G 联盟计划在新诊断的高危转移性尤文肉瘤患者中进行伊立替康的 II 期窗口研究。
患者于 2004 年 4 月至 2007 年 12 月期间招募。伊立替康以 600mg/m2 的剂量静脉输注 1 小时，每 21 天 1 次，共使用 2 个疗程。在第二疗程后通过对原发和转移部位的影像学评估和必要时进行骨髓取样来确定反应评估。
共招募了 23 名患者。有 2 名患者被认为对反应不可评估。5 名患者（24%）显示部分缓解。43 个疗程中有 4 名患者出现 3 级或 4 级腹泻，用洛哌丁胺治疗。
这是首报伊立替康在未经治疗的尤文肉瘤患者中的单药活性。与其他儿科肿瘤和其他喜树碱类似物如拓扑替康一样，单药活性仅适度。伊立替康在 ES 患者中的确切作用、剂量方案以及与其他药物的联合应用仍需要进一步研究。
