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用于治疗小细胞肺癌(SCLC)的血管生成抑制剂:7项随机对照试验的荟萃分析。

Angiogenesis inhibitors for the treatment of small cell lung cancer (SCLC): A meta-analysis of 7 randomized controlled trials.

作者信息

Li Qing, Wu Tao, Jing Li, Li Miao-Jing, Tian Tao, Ruan Zhi-Ping, Liang Xuan, Nan Ke-Jun, Liu Zhi-Yan, Yao Yu, Guo Hui

机构信息

Department of Medical Oncology, The First Affiliated Hospital of Xi'an JiaoTong University Department of Respiratory Medicine, Xi'an Central Hospital, Xi'an, Shaanxi, P.R. China.

出版信息

Medicine (Baltimore). 2017 Mar;96(13):e6412. doi: 10.1097/MD.0000000000006412.

Abstract

BACKGROUND

This study aimed to assess the effectiveness and safety of angiogenesis inhibitors for the treatment of patients with small cell lung cancer (SCLC) via meta-analysis.

METHODS

Electronic databases including PubMed, Embase, and Cochrane Library were searched to look for eligible studies through February 1, 2016. RCTs comprising angiogenesis inhibitors and nonangiogenesis inhibitors for SCLC patients were investigated. The extracted data including overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) were summarized. In addition, the common adverse events (AEs) were also explored.

RESULTS

There were 7 phase II/III RCTs, encompassing 1322 SCLC patients eligible for meta-analysis. In comparison to nonangiogenesis inhibitors, angiogenesis inhibitors treatment was not associated with improvement of PFS [HR = 0.87, 95% CI (0.74-1.02), P = 0.09), OS [HR = 0.99, 95% CI (0.88-1.12), P = 0.91], or ORR [OR = 1.12, 95% CI (0.85-1.47), P = 0.41). Also, there was no improvement in 1-year survival rate [OR = 0.96, 95% CI (0.74-1.19), P = 0.63)], 2-year survival rate [OR = 1.00, 95% CI (0.66-1.51), P = 1.00)] or 1-year progression-free survival rates [OR = 0.95, 95% CI (0.69-1.31), P = 0.76)]. However, from subgroup analyses, it was observed that angiogenesis inhibitors improved ORR [HR = 1.66 (95% CI 1.02-2.71), P = 0.04] in phase II studies and bevacizumab improved PFS [HR = 0.73 (95% CI 0.42-0.97), P = 0.04]. It is important to note that angiogenesis inhibitors reduced emesis [OR = 0.38, 95% CI (0.17-0.85), P = 0.02], but increased incidence of constipation [OR = 4.02, 95% CI (2.14-7.55), P < 0.0001) and embolism [OR = 2.24, 95% CI (1.45-3.47), P = 0.0003).

CONCLUSION

Adding angiogenesis inhibitors to chemotherapy did not improve PFS, OS, ORR, 1-year survival rate, 2-year survival rate or 1-year progression-free survival rate for SCLC. However, subgroup analysis revealed that bevacizumab enhanced PFS. Angiogenesis inhibitors also had a high incidence of constipation and embolism.

摘要

背景

本研究旨在通过荟萃分析评估血管生成抑制剂治疗小细胞肺癌(SCLC)患者的有效性和安全性。

方法

检索包括PubMed、Embase和Cochrane图书馆在内的电子数据库,以查找截至2016年2月1日的符合条件的研究。对包含血管生成抑制剂和非血管生成抑制剂治疗SCLC患者的随机对照试验(RCT)进行调查。总结提取的数据,包括总生存期(OS)、无进展生存期(PFS)和客观缓解率(ORR)。此外,还探讨了常见的不良事件(AE)。

结果

有7项II/III期RCT,共1322例SCLC患者符合荟萃分析条件。与非血管生成抑制剂相比,血管生成抑制剂治疗与PFS改善无关[风险比(HR)=0.87,95%置信区间(CI)(0.74 - 1.02),P = 0.09],OS改善无关[HR = 0.99,95% CI(0.88 - 1.12),P = 0.91],ORR改善无关[优势比(OR)=1.12,95% CI(0.85 - 1.47),P = 0.41]。1年生存率[OR = 0.96,95% CI(0.74 - 1.19),P = 0.63]、2年生存率[OR = 1.00,95% CI(0.66 - 1.51),P = 1.00]或1年无进展生存率[OR = 0.95,95% CI(0.69 - 1.31),P = 0.76]也无改善。然而,亚组分析显示,血管生成抑制剂在II期研究中改善了ORR[HR = 1.66(95% CI 1.02 - 2.71),P = 0.04],贝伐单抗改善了PFS[HR = 0.73(95% CI 0.42 - 0.97),P = 0.04]。需要注意的是,血管生成抑制剂减少了呕吐[OR = 0.38,95% CI(0.17 - 0.85),P = 0.02],但增加了便秘发生率[OR = 4.02,95% CI(2.14 - 7.55),P < 0.0001]和栓塞发生率[OR = 2.24,95% CI(1.45 - 3.47),P = 0.0003]。

结论

化疗中添加血管生成抑制剂并未改善SCLC的PFS、OS、ORR、1年生存率、2年生存率或1年无进展生存率。然而,亚组分析显示贝伐单抗可提高PFS。血管生成抑制剂还具有较高的便秘和栓塞发生率。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/244d/5380252/487bf6d9a655/medi-96-e6412-g001.jpg

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