A phase II study of aflibercept in patients with advanced epithelial ovarian cancer and symptomatic malignant ascites

详细信息	查看全文 | 推荐本文 |

• 作者：Nicoletta Colombo^a ; ^{nicoletta.colombo@ieo.it} ; Giorgia Mangili^b ; Serafina Mammoliti^c ; Må ; rten Kalling^d ; Bengt Tholander^e ; Lars Sternas^f ; Giliane Buzenet^g ; Donald Chamberlain^h
• 关键词：Aflibercept ; VEGF trap ; Ovarian cancer ; Malignant ascites ; Phase II study
• 刊名：Gynecologic Oncology
• 出版年：2012
• 期刊代码：295_00908258
• 类别：med
• 出版时间：April, 2012
• 卷：125
• 期：1
• 页码：42-47
• 文件大小：260 K

摘要

Objective

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.

Methods

Patients who required 鈮?#xA0;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 鈮?#xA0;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.