Department of Surgery, The Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Box 3624, Durham, NC 27710, USA.
Br J Cancer. 2009 Dec 15;101(12):1986-94. doi: 10.1038/sj.bjc.6605412. Epub 2009 Nov 17.
We evaluated bevacizumab with metronomic etoposide among recurrent malignant glioma patients in a phase 2, open-label trial.
A total of 59 patients, including 27 with glioblastoma (GBM) and 32 with grade 3 malignant glioma, received 10 mg kg(-1) bevacizumab biweekly and 50 mg m(-2) etoposide daily for 21 consecutive days each month. The primary end point was a 6-month progression-free survival, and secondary end points included safety and overall survival. Vascular endothelial growth factor (VEGF), VEGFR-2, carbonic anhydrase 9 (CA9) and hypoxia-inducible factor-2alpha (HIF-2alpha) were assessed semiquantitatively in archival tumours using immunohistochemistry and were correlated with outcome.
Among grade 3 and GBM patients, the 6-month progression-free survivals were 40.6% and 44.4%, the radiographic response rates were 22% and 37% and the median survivals were 63.1 and 44.4 weeks, respectively. Hypertension predicted better outcome among both grade 3 and GBM patients, whereas high CA9 and low VEGF were associated with poorer progression-free survival (PFS) among those with GBM. The most common grade > or = 3 adverse events included neutropaenia (24%), thrombosis (12%), infection (8%) and hypertension (3%). Two patients had asymptomatic, grade 1 intracranial haemorrhage and one on-study death occurred because of pulmonary embolism.
Bevacizumab with metronomic etoposide has increased toxicity compared with previous reports of bevacizumab monotherapy. Its anti-tumour activity is similar to that of bevacizumab monotherapy or bevacizumab plus irinotecan. (ClinicalTrials.gov: NCT00612430).
我们在一项 2 期、开放标签试验中评估了贝伐单抗联合米托蒽醌治疗复发性恶性脑胶质瘤患者的疗效。
共纳入 59 例患者，包括 27 例胶质母细胞瘤（GBM）和 32 例 3 级恶性脑胶质瘤患者，每月接受 10 mg/kg 贝伐单抗、50 mg/m2 米托蒽醌治疗，每 21 天为一个周期。主要终点为 6 个月无进展生存期，次要终点包括安全性和总生存期。采用免疫组化方法半定量检测存档肿瘤中血管内皮生长因子（VEGF）、血管内皮生长因子受体 2（VEGFR-2）、碳酸酐酶 9（CA9）和缺氧诱导因子 2α（HIF-2α），并分析其与预后的相关性。
3 级和 GBM 患者的 6 个月无进展生存率分别为 40.6%和 44.4%，影像学缓解率分别为 22%和 37%，中位生存期分别为 63.1 周和 44.4 周。高血压是 3 级和 GBM 患者预后较好的预测因素，而高 CA9 和低 VEGF 与 GBM 患者无进展生存期较差相关。最常见的 3 级以上不良事件包括中性粒细胞减少（24%）、血栓形成（12%）、感染（8%）和高血压（3%）。2 例患者出现无症状、1 级颅内出血，1 例研究期间死亡与肺栓塞有关。
与贝伐单抗单药治疗的既往报告相比，贝伐单抗联合米托蒽醌治疗的毒性增加。其抗肿瘤活性与贝伐单抗单药或贝伐单抗联合伊立替康治疗相似。（ClinicalTrials.gov：NCT00612430）。
