Salvage bevacizumab (rhuMAB VEGF)-based therapy after multiple prior cytotoxic regimens in advanced refractory epithelial ovarian cancer
Salvage bevacizumab (rhuMAB VEGF)-based therapy after multiple prior cytotoxic regimens in advanced refractory epithelial ovarian cancer
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DOI：
10.1016/j.ygyno.2006.05.006
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发表时间：
2006-08-01
影响因子：
4.7
通讯作者：
Burger, Robert A.
中科院分区：
文献类型：
--
作者：
Monk, Bradley J.;Han, Ernest;Burger, Robert A.
目标.贝伐单抗（BEV）是一种抗血管内皮生长因子的人源化单克隆抗体。我们回顾了BEV治疗多次化疗失败的复发性晚期卵巢上皮癌患者的经验。32名未参与正在进行的临床试验的患者接受BEV治疗（15 mg/kg，每3周一次IV）。从患者图表中提取人口统计学和临床病理数据、临床结局和不良事件。回顾性应用RECIST和CA-125 Rustin标准评价缓解和进展。使用Kaplan-Meier方法确定中位无进展生存期（PFS）和总生存期（OS）。采用不良事件通用术语标准第3版对不良事件进行回顾性分类。患者的中位年龄为57岁（范围35-80岁），84%为白人，50%的GOG体能状态为2。FIGO分期包括80%的III期和10%的TV期。肿瘤主要为2级（29%）和3级（64%）以及浆液性组织学亚型（69%）。所有患者在BEV之前都有多次既往细胞毒性化疗失败（中位数为5（范围2-10））。中位随访时间为4.8个月（范围0.4-16.3）。23例患者接受BEV单药治疗，2例患者接受BEV联合另一种化疗方案（5-FU/lecovorin+奥沙利铂、环磷酰胺）治疗，8例患者最初接受BEV单药治疗，随后接受BEV联合卡西他滨、环磷酰胺、多西他赛、卡铂或每周紫杉醇治疗。中位6个周期（范围1-20），共给予196剂BEV。1例患者在第1周期后失访。我们观察到16%的缓解率（所有仅用BEV治疗的患者），62.5%的患者表现出稳定的疾病。中位OS为6.9个月，中位PFS为5.5个月。观察到3例3级不良事件，未观察到4级不良事件。3级毒性包括高血压、蛋白尿和肠外瘘。1例患者在BEV之前接受了7次减积手术，在BEV 5个周期后发生瘘。BEV通常在多次既往细胞毒性方案后耐受良好，并在复发性卵巢癌女性中产生显著的临床获益。(c)2006年爱思唯尔公司All rights reserved.
Objectives. Bevacizumab (BEV) is a humanized monoclonal antibody against vascular endothelial growth factor. We reviewed our experience with BEV in patients with recurrent advanced epithelial ovarian cancer who had failed multiple prior chemotherapeutic regimens.Methods. Thirty-two patients not participating in an ongoing clinical trial were treated with BEV (15 mg/kg every 3 weeks IV). Demographic and clinicopathologic data, clinical outcomes, and adverse events were extracted from patient charts. RECIST and CA-125 Rustin criteria were retrospectively applied to evaluate response and progression. Median progression-free survival (PFS) and overall survival (OS) were determined using Kaplan-Meier methods. Adverse events were retrospectively categorized using the common terminology criteria for adverse events version 3.Results. The median patient age was 57 years (range 35-80) with 84% being Caucasian and 50% having a GOG performance status of 2. FIGO stages included 80% stage III and 10% stage TV. The tumors were mostly grades 2 (29%) and 3 (64%) and serous histological subtype (69%). All patients had failed multiple prior cytotoxic chemotherapies (median of 5 (range 2-10)) prior to BEV. The median duration of follow-up was 4.8 months (range 0.4-16.3). Twenty-three patients were treated with BEV alone, 2 received BEV with another chemotherapy regimen (5-FU/lecovorin plus oxaliplatin, cyclophosphamide), and 8 initially received BEV alone, followed by BEV with capcitabine, cyclophosphamide, docetaxel, carboplatin, or weekly paclitaxel. A median of 6 cycles (range 1-20) with 196 total doses of BEV was administered. One patient was lost to follow-up after cycle 1. We observed a 16% response rate (all in those treated with BEV alone) with 62.5% of patients demonstrating stable disease. Median OS was 6.9 months, and the median PFS was 5.5 months. Three grade 3 and no grade 4 adverse events were observed. Grade 3 toxicities included hypertension, proteinuria, and enterocutaneous fistula. The fistula occurred after 5 cycles of BEV in a patient who had undergone 7 debulking surgeries prior to BEV.Conclusions. BEV is generally well tolerated after multiple prior cytotoxic regimens and results in significant clinical benefit among women with recurrent ovarian cancer. (c) 2006 Elsevier Inc. All rights reserved.