A Phase II Window Study of Irinotecan (CPT-11) in High Risk Ewing Sarcoma: A Euro-EWING Study
A Phase II Window Study of Irinotecan (CPT-11) in High Risk Ewing Sarcoma: A Euro-EWING Study
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DOI：
10.1002/pbc.24767
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发表时间：
2014-03-01
影响因子：
3.2
通讯作者：
Whelan, J. S.
中科院分区：
文献类型：
--
作者：
Morland, B.;Platt, K.;Whelan, J. S.
非肺转移性尤文肉瘤患者的预后仍然很差，生存率在15- 20%之间。将有效的新药引入临床实践的必要性是明确的。基于异种移植反应的临床前原理和儿童I期研究的支持，Euro-E.W.I.N.G联盟计划在新诊断的高风险转移性尤文肉瘤患者中进行伊立替康的II期窗口研究。伊立替康600 mg/m2，间隔21天，每次1小时，共2个疗程。反应评估后，第二个疗程的治疗原发性和转移部位的放射性评估，并在适当的骨髓sampling. Results 23例患者被招募。2例患者的缓解被视为不可评价。5名患者（24%）表现出部分缓解。在4/43的治疗过程中出现3级或4级腹泻，并与洛哌丁胺进行管理。ConclusionsThis是第一次报告单药伊立替康活性在未经治疗的尤文肉瘤患者人群。与其他儿科肿瘤和其他喜树碱类似物（如托泊替康）一样，单药活性仅为中等。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用药仍需进一步研究。儿科血液癌症2014;61：442-445。(c)2013 Wiley Periodicals，Inc.
BackgroundThe 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.ProceduresPatients were recruited between April 2004 and December 2007. Two courses of irinotecan were administered at a dose of 600mg/m(2) as a 1hour 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.ResultsTwenty-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.ConclusionsThis 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. Pediatr Blood Cancer 2014;61:442-445. (c) 2013 Wiley Periodicals, Inc.