Efficacy of Imatinib in Aggressive Fibromatosis: Results of a Phase II Multicenter Sarcoma Alliance for Research through Collaboration (SARC) Trial
Efficacy of Imatinib in Aggressive Fibromatosis: Results of a Phase II Multicenter Sarcoma Alliance for Research through Collaboration (SARC) Trial
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DOI：
10.1158/1078-0432.ccr-10-1177
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发表时间：
2010-10-01
影响因子：
11.5
通讯作者：
Baker, Laurence H.
中科院分区：
文献类型：
--
作者：
Chugh, Rashmi;Wathen, J. Kyle;Baker, Laurence H.
目的：侵袭性纤维瘤病（AF;硬纤维瘤）是罕见的结缔组织克隆性肿瘤增殖，尽管广泛的手术切除和/或放射治疗，其仍可能是局部侵袭性的。Sarcoma Alliance for Research through Collaboration（SARC）启动了一项前瞻性II期试验，旨在研究AF或10种肉瘤亚型之一患者接受伊马替尼（一种多种酪氨酸激酶抑制剂）治疗的结局。在这里，我们特别报告的AF患者的结果以及评估进行检查imatinib.Experimental Design的机制：患者>= 10岁硬纤维瘤是不能治愈的手术治疗或在其中根治性手术将导致不良的功能障碍是合格的。伊马替尼的处方剂量为300 mg每日两次[体表面积（BSA）≥ 1.5 m（2）]，200 mg每日两次（BSA = 1.0-1.49 m（2））或100 mg每日两次（BSA < 1.0 m（2））。评估了2个月和4个月时的缓解结局。通过免疫组织化学分析组织标本的cKIT、血小板衍生生长因子受体α（PDGFR α）、PDGFR β、AKT、PTEN、FKHR和β-连环蛋白的表达。通过等位基因识别PCR分析肿瘤DNA的PDGFR α外显子18和APC突变。既往治疗方案的中位数量为1。Kaplan-Meier估计的2和4个月无进展生存率分别为94%和88%，1年无进展生存率为66%。客观缓解率为6%（3/51）。靶蛋白的表达和多态性被确定在组织样本中，但没有显着的相关性与结果被观察到使用的samples available.Conclusion：伊马替尼可能有一个不可切除或难以切除硬纤维瘤的管理中的作用。Clin Cancer Res; 16（19）; 4884-91. (C)2010年AACR。
Purpose: Aggressive fibromatoses (AF; desmoid tumors) are rare clonal neoplastic proliferations of connective tissues that can be locally aggressive despite wide surgical resection and/or radiation therapy. The Sarcoma Alliance for Research through Collaboration (SARC) initiated a prospective phase II trial to investigate the outcome of patients treated with imatinib, a multiple tyrosine kinase inhibitor, in patients with AF, or 1 of 10 sarcoma subtypes. Here, we report specifically on the outcome of patients with AF as well as evaluations undertaken to examine the mechanism of imatinib.Experimental Design: Patients >= 10 years old with desmoid tumors that were not curable by surgical management or in whom curative surgery would lead to undesirable functional impairment were eligible. Imatinib was prescribed at 300 mg twice daily [body surface area (BSA) >= 1.5 m(2)], 200 mg twice daily (BSA = 1.0-1.49 m(2)), or 100 mg twice daily (BSA < 1.0 m(2)). Response outcomes at 2 and 4 months were assessed. Tissue specimens were analyzed by immunohistochemistry for expression of cKIT, platelet-derived growth factor receptor alpha (PDGFR alpha), PDGFR beta, AKT, PTEN, FKHR, and beta-catenin. Tumor DNA was analyzed for PDGFR alpha exon 18 and APC mutations by allelic discrimination PCR.Results: Fifty-one patients were enrolled. The median number of prior regimens was 1. Kaplan-Meier estimates of 2- and 4-month progression-free survival rates were 94% and 88%, respectively, and 1-year progression-free survival was 66%. Objective response rate was 6% (3 of 51). Expression and polymorphisms of target proteins were identified in tissue samples, but no significant correlation with outcome was observed using the samples available.Conclusion: Imatinib may have a role in the management of unresectable or difficult to resect desmoid tumors. Clin Cancer Res; 16(19); 4884-91. (C) 2010 AACR.