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抗血管生成药物联合化疗用于复发性卵巢癌患者的荟萃分析。

Antiangiogenic drugs used with chemotherapy for patients with recurrent ovarian cancer: a meta-analysis.

作者信息

Yi SuYi, Zeng LongJia, Kuang Yan, Cao ZhiJuan, Zheng ChengJun, Zhang Yue, Liao Meng, Yang Lu

机构信息

Department of Gynaecology and Obstetrics, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People's Republic of China.

出版信息

Onco Targets Ther. 2017 Feb 17;10:973-984. doi: 10.2147/OTT.S119879. eCollection 2017.

Abstract

OBJECTIVE

The value of antiangiogenic inhibitors for patients with recurrent ovarian cancer has not been completely affirmed. Therefore, we aimed to assess the effectiveness and toxicities of various antiangiogenic drugs for the treatment of recurrent ovarian cancer.

METHODS

In this meta-analysis, we searched PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials databases for complete randomized controlled trials. The searches were extended to May 15, 2016. The risk of bias of the included studies was evaluated via a Cochrane systematic evaluation, and the statistical analyses were performed using RevMan 5.2 software.

RESULTS

In total, we included 8 randomized controlled trials involving 3,211 patients and divided them into 3 groups, vascular endothelial growth factor receptor inhibitors (VEGFRIs), vascular endothelial growth factor (VEGF) inhibitors (bevacizumab), and angiopoietin inhibitors (trebananib). The progression-free survival improved significantly in all the groups being given antiangiogenic drugs (hazard ratio [HR]: 0.55, 95% confidence interval [CI]: 0.45-0.67, =0%, <0.00001 for the VEGFRI group; HR: 0.53, 95% CI: 0.45-0.63, =51%, <0.00001 for the VEGF inhibitor group; HR: 0.67, 95% CI: 0.58-0.77, =0%, <0.00001 for the trebananib group). Overall survival was obviously prolonged in the VEGFRI (HR: 0.76, 95% CI: 0.59-0.97, =0%, =0.03), the VEGF inhibitor (HR: 0.87, 95% CI: 0.77-0.99, =0%, =0.03), and trebananib groups (HR: 0.81, 95% CI: 0.67-0.99, =0%, =0.04). The incidence of grade 3/4 side effects was different among the 3 groups, for example, proteinuria, hypertension, gastrointestinal perforation, and arterial thromboembolism were presented in the VEGF inhibitor group. Increased incidences of fatigue, diarrhea, and hypertension were seen in the VEGFRI group, and the trebananib group had a higher incidence of hypokalemia.

CONCLUSION

This meta-analysis showed that antiangiogenic drugs improved the progression-free survival. The VEGFRI, bevacizumab, and trebananib groups showed increased overall survival. Adding antiangiogenic drugs to chemotherapy treatment resulted in a higher incidence of grade 3/4 side effects, but these were manageable.

摘要

目的

抗血管生成抑制剂对复发性卵巢癌患者的价值尚未得到完全肯定。因此,我们旨在评估各种抗血管生成药物治疗复发性卵巢癌的有效性和毒性。

方法

在这项荟萃分析中,我们检索了PubMed、EMBASE和Cochrane对照试验中央注册库数据库,以查找完整的随机对照试验。检索范围截至2016年5月15日。通过Cochrane系统评价评估纳入研究的偏倚风险,并使用RevMan 5.2软件进行统计分析。

结果

我们总共纳入了8项随机对照试验,涉及3211名患者,并将他们分为3组,即血管内皮生长因子受体抑制剂(VEGFRIs)组、血管内皮生长因子(VEGF)抑制剂(贝伐单抗)组和血管生成素抑制剂(曲贝替尼)组。所有接受抗血管生成药物治疗的组的无进展生存期均显著改善(风险比[HR]:0.55,95%置信区间[CI]:0.45 - 0.67,VEGFRIs组P = 0%,P < 0.00001;HR:0.53,95% CI:0.45 - 0.63,VEGF抑制剂组P = 51%,P < 0.00001;HR:0.67,95% CI:0.58 - 0.77,曲贝替尼组P = 0%,P < 0.00001)。VEGFRIs组(HR:0.76,95% CI:0.59 - 0.97,P = 0%,P = 0.03)、VEGF抑制剂组(HR:0.87,95% CI:0.77 - 0.99,P = 0%,P = 0.03)和曲贝替尼组(HR:0.81,95% CI:0.67 - 0.99,P = 0%,P = 0.04)的总生存期均明显延长。3组中3/4级副作用的发生率有所不同,例如,VEGF抑制剂组出现蛋白尿、高血压、胃肠道穿孔和动脉血栓栓塞。VEGFRIs组疲劳、腹泻和高血压的发生率增加,曲贝替尼组低钾血症的发生率较高。

结论

这项荟萃分析表明,抗血管生成药物改善了无进展生存期。VEGFRIs组、贝伐单抗组和曲贝替尼组的总生存期均有所延长。在化疗中添加抗血管生成药物导致3/4级副作用的发生率更高,但这些副作用是可控的。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc60/5322854/a3d284c2a017/ott-10-973Fig1.jpg

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