A phase II study of imatinib mesylate in children with refractory or relapsed solid tumors: A children's oncology group study
A phase II study of imatinib mesylate in children with refractory or relapsed solid tumors: A children's oncology group study
复制标题
DOI：
10.1002/pbc.21132
复制
发表时间：
2008-02-01
影响因子：
3.2
通讯作者：
Adamson, Peter C.
中科院分区：
文献类型：
--
作者：
Bond, Mason;Bernstein, Mark L.;Adamson, Peter C.
背景资料。甲磺酸伊马替尼是某些酪氨酸激酶的小分子抑制剂，最著名的是在慢性粒细胞白血病中发现的嵌合BCR-ABL融合蛋白。它还在体外抑制KIT和PDGF受体酪氨酸激酶。尤文肉瘤、骨肉瘤、神经母细胞瘤、促结缔组织增生性小圆细胞瘤、滑膜肉瘤常过度表达KIT或PDGF受体。伊马替尼在儿童和年轻人中进行了11期研究，这些患者患有选定的实体肿瘤。程序。年龄在30岁以下的难治性或复发性尤文肉瘤、骨肉瘤、神经母细胞瘤、促结缔组织增生性小圆细胞瘤、滑膜肉瘤或胃肠道间质瘤患者均符合条件。伊马替尼440 mg/m(2)/d，每日1次，疗程28天。根据实体瘤疗效评价标准(RECIST)进行疗效评定。结果。70名符合条件的患者入选，其中男性48名，女性22名，其中59名可评估疗效。在24例尤文肉瘤患者中，仅有一例部分缓解。没有其他客观的回应。有7名肺部病变的患者出现出血性胸腔积液，其中4人在出血时有进展性疾病。另有三名患者报告肿瘤内出血。结论。单药剂量为440 mg/m(2)/d的伊马替尼在儿童复发或难治性尤文肉瘤、骨肉瘤、神经母细胞瘤或促结缔组织增生性小圆细胞肿瘤中表现出很少或没有活性。
Background. Imatinib mesylate is a small molecule inhibitor of certain tyrosine kinases, most notably the chimeric bcr-abl fusion protein found in CML. It also inhibits KIT and PDGF receptor tyrosine kinases in vitro. Ewing sarcoma, osteosarcoma, neuroblastoma, desmoplastic small round cell, and synovial sarcomas often over-express KIT or the PDGF receptor. A phase 11 Study of imatinib in children and young adults with select solid tumors was performed. Procedure. Patients less than 30 years of age with refractory or recurrent Ewing sarcoma, osteosarcoma, neuroblastoma, desmoplastic small round cell, synovial sarcomas or GIST were eligible. Imatinib was administered daily for 28 day courses at a dose of 440 mg/m(2)/day. Responses were assessed according to Response Evaluation Criteria in Solid Tumor (RECIST). Results. Seventy eligible patients, 48 male and 22 female, were enrolled and 59 were evaluable for response. Only one partial response was seen among 24 patients with Ewing sarcoma. There were no other objective responses. Hemorrhagic pleural effusions occurred in seven patients with pulmonary lesions, four of whom had progressive disease at the time of the hemorrhage. Intratumoral bleeding was reported in three additional patients. Conclusion. Imatinib as a single agent at a dose of 440 mg/m(2)/day demonstrated little or no activity as a single agent in children with relapsed or refractory Ewing sarcoma, osteosarcoma, neuroblastoma, or desmoplastic small round cell tumors.