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多靶点受体酪氨酸激酶抑制剂联合化疗治疗晚期非小细胞肺癌的Meta分析
         
Multitargeted antiangiogenic tyrosine kinase inhibitors in combination with chemotherapy in patients with advanced non-small cell lung cancer:a Meta-analysis

摘    要
目的: 系统评价多靶点受体酪氨酸激酶抑制剂(tyrosine kinase inhibitor,TKI)联合化疗与单纯化疗治疗晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)的疗效和安全性。方法: 检索EMBASE、Cochrane Library、PubMed、中国知网、万方、维普和中国生物医学文献等数据库。按照文献纳入标准和排除标准选择临床随机对照试验(randomized controlled trial,RCT),评价文献质量,并提取资料。应用Stata 12.0软件进行Meta分析。结果: 纳入9项RCT,包括5286例患者。Meta分析结果显示,在所有入选研究中,多靶点受体TKI联合化疗组与单纯化疗组的客观缓解率(objective response rate,ORR)(比值比为1.51,95%可信区间为1.21~1.87,P=0.000)和无进展生存(progression-free survival,PFS)时间(风险比为0.83,95%可信区间为0.77~0.88,P=0.000)差异有统计学意义。两组的总生存(overall survival,OS)时间(风险比为0.94,95%可信区间为0.87~1.01,P=0.081)比较,差异无统计学意义。在不良反应方面,多靶点受体TKI联合化疗可提高腹泻(比值比为2.09,95%可信区间为1.48~2.96,P=0.000)、皮疹(比值比为2.30,95%可信区间为1.59~3.29,P=0.000)、高血压(比值比为3.30,95%可信区间为2.69~4.06,P=0.000)、出血(比值比为1.49,95%可信区间为1.07~2.06,P=0.018)、厌食(比值比为1.45,95%可信区间为1.01~2.07,P=0.042)、口腔炎(比值比为2.13,95%可信区间为1.29间为1.77~11.71,P=0.002)发生率。结论: 多靶点受体TKI联合化疗治疗晚期NSCLC的疗效优于单纯化疗方案。在安全性方面,多靶点受体TKI可增加腹泻、皮疹、高血压、出血、厌食、口腔炎和手足皮肤反应发生率,在临床应用时必须加强预防和对症治疗。
标    签   非小细胞肺   药物疗法   多靶点受体酪氨酸激酶抑制剂   随机对照试验   Meta分析   Neoplasms   non-small cell lung   Drug therapy   Multitargeted receptor tyrosine kinase inhibitor   Randomized controlled trial   Meta analysis  
 
Abstract
Objective: To evaluate the efficacy and safety of chemotherapy alone or combined with multitargeted antiangiogenic TKI (tyrosine kinase inhibitor) for patients with advanced NSCLC (non-small cell lung cancer). Methods: A computer-based online search was performed by using EMBASE, Cochrane Library, PubMed, CNKI (China National Knowledge Infrastructure), Wanfang and VIP databases and Chinese Biomedical Literature Database. Studies of RCT (randomized controlled trial) in accordance with the inclusion and exclusion criteria were included. Quality of the studies was assessed using Jadad score. Data were extracted from the studies by 2 independent reviewers. The Meta-analysis was performed by Stata 12.0 software. Results: Nine RCTs (totally 5 286 patients) were eligible. Meta-analysis showed that there was significant improvement in ORR (objective response rate)[OR (odds ratio):1.51, 95% CI (confidence interval):1.21-1.87, P=0.000] and PFS (progression-free survival)[HR (hazard ratio):0.83, 95% CI:0.77-0.88, P=0.000) in multitargeted antiangiogenic TKI plus chemotherapy group, as compared with chemotherapy along group. Though the pooled HR (HR=0.94, 95% CI:0.87-1.01, P=0.081) for OS (overall survival) showed no significant difference between the two groups. However, there were higher rates of diarrhea (OR:2.09, 95% CI:1.48-2.96, P=0.000), rash (OR:2.30, 95% CI:1.59-3.29, P=0.000), hypertension (OR:3.30, 95% CI:2.69-4.06, P=0.000), hemorrhage (OR:1.49, 95% CI:1.07-2.06, P=0.018), anorexia (OR:1.45, P=1.01-2.07, P=0.042), stomatitis (OR:2.13, 95% CI:1.29-3.52, P=0.003) and hand-foot skin reaction (OR:4.55, 95% CI:1.77-11.71, P=0.002). Conclusion: In comparison with chemotherapy alone, multitargeted antiangiogenic TKI plus chemotherapy had better therapeutic effects on NSCLC. Meanwhile, it also increases the rates of adverse effects such as diarrhea, rash, hypertension, hemorrhage, anorexia, stomatitis and hand-foot skin reaction, which should be prevented and symptomatically treated.

中图分类号 R734.2   DOI 10.3781/j.issn.1000-7431.2013.09.007

 
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所属栏目 临床研究

基金项目 国家自然科学基金资助项目(编号:81102038)

收稿日期 2013/4/16

修改稿日期 2013/5/14

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引用该论文: TIAN Cong,TANG Li-na,QI Wei-xiang,LIN Feng,LI Hong-tao,YAO Yang. Multitargeted antiangiogenic tyrosine kinase inhibitors in combination with chemotherapy in patients with advanced non-small cell lung cancer:a Meta-analysis[J]. Tumor, 2013, 33(9): 786~794
田聪,汤丽娜,祁伟祥,林峰,李洪涛,姚阳. 多靶点受体酪氨酸激酶抑制剂联合化疗治疗晚期非小细胞肺癌的Meta分析[J]. 肿瘤, 2013, 33(9): 786~794


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