A phase II study of aflibercept in patients with advanced epithelial ovarian cancer and symptomatic malignant ascites
A phase II study of aflibercept in patients with advanced epithelial ovarian cancer and symptomatic malignant ascites
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DOI：
10.1016/j.ygyno.2011.11.021
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发表时间：
2012-04-01
影响因子：
4.7
通讯作者：
Chamberlain, Donald
中科院分区：
文献类型：
--
作者：
Colombo, Nicoletta;Mangili, Giorgia;Chamberlain, Donald
目的：重组融合蛋白阿柏西普结合并中和血管内皮生长因子（VEGF）A、B和胎盘生长因子（PlGF）。在卵巢癌模型中，阿柏西普抑制腹水形成并降低肿瘤负荷。这项开放标签、单臂、多中心II期研究评估了阿柏西普治疗晚期化疗耐药上皮性卵巢癌和有症状的恶性腹水患者的疗效和安全性。方法：需要>= 3次穿刺的患者，每月1-4次穿刺，每2周静脉注射阿柏西普4 mg/kg。主要终点是重复穿刺应答率（RPRR），应答定义为重复穿刺的时间比基线interval.Results增加至少两倍，16例入选患者中有10例获得应答，RPRR为62.5%（95%CI 35.4%-84.8%）。基于RPRR>= 60%的假设，认为阿柏西普有效。重复穿刺的中位时间为76.0（95% CI 64.0-178.0）天，是基线间隔（16.8天）的4.5倍。中位无进展生存期为59.5（95%CI 41.0-83.0）天。12例患者发生了认为与阿柏西普治疗相关的不良事件，包括高血压（7例患者）、头痛、厌食和发音困难（各3例患者）。2例患者发生3/4级治疗相关不良事件（1例患者发生3级高血压和体重减轻，1例患者发生3级肠穿孔）。结论：阿柏西普4 mg/kg每2周给药一次可有效控制恶性腹水，缩短重复穿刺间隔。安全性特征与报告的抗VEGF药物一致。(C)2011 Elsevier Inc. All rights reserved.
Objective: The recombinant fusion protein, aflibercept binds and neutralizes vascular endothelial growth factor (VEGF) A, B and placental growth factor (PIGF). Aflibercept inhibits ascites formation and reduces tumor burden in an ovarian cancer model. This open-label, single-arm, multicenter phase II study assessed the efficacy and safety of aflibercept in patients with advanced chemo-resistant epithelial ovarian cancer and symptomatic malignant ascites.Methods: Patients who required >= 3 previous paracenteses at 1-4 paracenteses per month received intravenous aflibercept 4 mg/kg every 2 weeks. The primary endpoint was repeat paracentesis response rate (RPRR), with response defined as at least a two-fold increase in time to repeat paracentesis compared with the baseline interval.Results: Ten out of 16 enrolled patients achieved a response; the RPRR was 62.5% (95% CI 35.4%-84.8%). Aflibercept was considered effective based on a hypothesis that the RPRR was >= 60%. Median time to repeat paracentesis was 76.0 (95% CI 64.0-178.0) days, which was 4.5 times longer than the baseline interval (16.8 days). Median progression-free survival was 59.5 (95% CI 41.0-83.0) days. Twelve patients experienced adverse events considered related to aflibercept treatment including hypertension (7 patients), headache, anorexia, and dysphonia (3 patients each). Two patients experienced Grade 3/4 treatment-related adverse events (Grade 3 hypertension and weight loss in one patient, Grade 3 intestinal perforation in one patient).Conclusion: Aflibercept 4 mg/kg every 2 weeks was effective at controlling malignant ascites, reducing the interval between repeat paracenteses. The safety profile was consistent with that reported for anti-VEGF agents. (C) 2011 Elsevier Inc. All rights reserved.