A phase II trial of thalidomide in patients with refractory leiomyosarcoma of the uterus and correlation with biomarkers of angiogenesis: A gynecologic oncology group study
A phase II trial of thalidomide in patients with refractory leiomyosarcoma of the uterus and correlation with biomarkers of angiogenesis: A gynecologic oncology group study
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DOI：
10.1016/j.ygyno.2007.05.013
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发表时间：
2007-09-01
影响因子：
4.7
通讯作者：
Benbrook, Doris
中科院分区：
文献类型：
--
作者：
McMeekin, D. Scott;Sill, Michael W.;Benbrook, Doris
客观性。目的评价沙利度胺对已治疗、可测量、持续性或复发性子宫A平滑肌肉瘤(LMS)的疗效和不良反应，并探讨血管生成标志物与治疗或临床结果的关系。符合条件的同意的患者接受治疗，直到疾病进展或毒性干预，每天开始剂量为200毫克/天，每两周增加200毫克，目标剂量为1000毫克/天。终点包括无进展生存期A(PFS)和6个月、毒性、反应性、PFS和生存期。检测治疗前后血清和血浆中血管内皮生长因子(VEGF)、碱性成纤维细胞生长因子(BFGF)和可溶性内皮蛋白C受体(SEPCR)的水平。在入选的30名患者中，有一名不合格(组织学错误)。中位年龄56岁。在29名符合条件的患者中，7名患者达到了目标剂量，只有2名患者接受了超过4个周期的治疗。两名患者(7%)经历了PFS和GT；=6个月。无客观反应，7例(24%)病情稳定，19例(66%)进展，3例(10%)无反应。中位PFS为1.9个月，中位总生存期为8.3个月。未观察到4级不良反应。最常见的3级不良反应是神经系统(6例)、肺部(4例)和躯体(3例)。沙利度胺治疗可显著降低血浆碱性成纤维细胞生长因子(P=0.008)和血清sEPCR值(P=0.006)，但与血浆血管内皮生长因子水平无关。血浆血管内皮生长因子水平与疾病进展(危险比[HR]=3.5；95%可信区间(C)1.5~7.8；p=0.003)和死亡风险(HR=4.7；95%CI=1.6~13.8；p=0.005)相关。沙利度胺在子宫LMS患者中不起作用，并且不改变VEGF浓度。在这一人群中，治疗前的血管内皮生长因子和预后之间的相关性支持了对子宫LMS抗血管生成治疗的进一步评估。(C)2007年，爱思唯尔公司出版。
Objeetives. To evaluate the efficacy and adverse events (AEs) of thalidomide in previously treated, measurable, persistent or recurrent A leiomyosarcoma (LMS) of the uterus, and to explore associations between angiogenic markers and treatment or clinical outcome.Methods. Eligible, consenting patients were treated until disease progression or toxicity intervened with daily starting dose of 200 mg thalidomide/day that was increased by 200 mg every 2 weeks to a target dose of 1000 mg/day. End-points included progression-free survival A (PFS) >: 6 months, toxicity, response, PFS and survival. Vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and soluble endothelial protein C receptor (sEPCR) were evaluated in pre- and post-treatment serum and plasma.Results. Of 30 enrolled patients, one was ineligible (wrong histology). Median age was 56 years. Among 29 eligible patients, seven reached the target dose and only two received more than 4 cycles. Two patients (7%) experienced PFS >= 6 months. There were no objective responses, seven (24%) had stable disease, 19 (66%) progressed and 3 (10%) were not evaluable for response. Median PFS was 1.9 months and median overall survival was 8.3 months. Grade 4 AEs were not observed. The most common grade 3 AEs were neurologic (6), pulmonary (4) and constitutional (3). Treatment with thalidomide was associated with a significant decrease in plasma bFGF (p = 0.008) and serum sEPCR (P = 0.006), but not in plasma VEGF. Plasma VEGF was associated with increased risk of progression (hazard ratio [HR] =3.5; 95% confidence interval (C) 1.5-7.8; p=0.003) and death (HR = 4.7; 95% CI = 1.6-13.8; p=0.005) after adjusting for GOG performance status.Conclusions. Thalidomide was not active in patients with uterine LMS and did not alter VEGF concentration. The association between pretreatment VEGF and prognosis in this population supports further evaluation of anti-angiogenic therapies in uterine LMS. (c) 2007 Published by Elsevier Inc.