Istituto Europeo di Oncologia, Divisione di Ginecologia, Via Ripamonti, Milano, Italy.
Gynecol Oncol. 2012 Apr;125(1):42-7. doi: 10.1016/j.ygyno.2011.11.021. Epub 2011 Nov 21.
The recombinant fusion protein, aflibercept binds and neutralizes vascular endothelial growth factor (VEGF) A, B and placental growth factor (PlGF). 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.
Patients who required ≥3 previous paracenteses at 1-4 paracenteses per month received intravenous aflibercept 4mg/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.
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).
Aflibercept 4mg/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.
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）。阿柏西普可抑制腹水形成并减少卵巢癌模型中的肿瘤负担。这项开放标签、单臂、多中心 II 期研究评估了阿柏西普在晚期化疗耐药上皮性卵巢癌和有症状恶性腹水患者中的疗效和安全性。
每月需要 1-4 次引流且需要至少 3 次引流的患者，给予静脉注射阿柏西普 4mg/kg，每 2 周一次。主要终点为重复引流反应率（RPRR），反应定义为与基线间隔相比，重复引流时间至少增加两倍。
16 名入组患者中有 10 名患者达到了缓解；RPRR 为 62.5%（95%CI 35.4%-84.8%）。根据 RPRR≥60%的假设，认为阿柏西普是有效的。重复引流的中位时间为 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 名患者出现了与阿柏西普治疗相关的不良事件，包括高血压（7 例）、头痛、厌食和发音困难（各 3 例）。2 名患者出现了 3/4 级治疗相关不良事件（1 例高血压，1 例体重减轻；1 例肠穿孔）。
阿柏西普 4mg/kg，每 2 周一次，可有效控制恶性腹水，减少重复引流的间隔。安全性与抗 VEGF 药物报告的安全性一致。
