贝伐珠单抗治疗非小细胞肺癌所致恶性胸腔积液的研究进展
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摘要
肺癌是全球范围内发病率最高的恶性肿瘤,晚期肺癌所致的恶性胸腔积液(malignant pleural effusion,MPE)严重影响患者的生活质量和预后。MPE的治疗手段包括胸腔穿刺术、胸膜固定术、胸腔埋管引流、胸腔内灌注治疗等。血管内皮生长因子(vascular endothelial growth factor, VEGF)及其受体是一组影响血管生成的重要配体和受体,是控制血管生成的主要因素,在MPE的形成中发挥重要作用。贝伐珠单抗是一种重组的人源化VEGF单克隆抗体,可与内源性VEGF竞争性结合VEGF受体,抑制新血管生成以及降低血管通透性,阻碍胸腔积液形成,延缓肿瘤发展进程。本综述旨在讨论贝伐珠单抗治疗非小细胞肺癌所致恶性胸腔积液的研究进展,探讨贝伐珠单抗临床应用的方法、疗效、安全性以及未来的发展方向。
Lung cancer is the most commonly diagnosed cancer worldwide. Malignant pleural effusion(MPE) caused by advanced lung cancer seriously affect the patients' quality of life and prognosis. The management of MPE includes thoracentesis, pleurodesis, indwelling pleural catheters and drug perfusion in pleural cavity. Vascular endothelial growth factor(VEGF) and its receptor are a group of important ligands and receptors that affect angiogenesis. They are the main factors controlling angiogenesis, and they play an important role in the formation of MPE. Bevacizumab is a recombinant humanized VEGF monoclonal antibody, competitively binding to endogenous VEGF receptor. Bevacizumab can inhibit new blood vessel formation, reduce vascular permeability, prevent pleural effusion accumulation and slow the growth of cancers. This review aims to discuss the progress of bevacizumab in the treatment of MPE caused by non-small cell lung cancer(NSCLC), and explore the clinical application, efficacy, safety and future direction of bevacizumab.
Lung cancer is the most commonly diagnosed cancer worldwide. Malignant pleural effusion(MPE) caused by advanced lung cancer seriously affect the patients' quality of life and prognosis. The management of MPE includes thoracentesis, pleurodesis, indwelling pleural catheters and drug perfusion in pleural cavity. Vascular endothelial growth factor(VEGF) and its receptor are a group of important ligands and receptors that affect angiogenesis. They are the main factors controlling angiogenesis, and they play an important role in the formation of MPE. Bevacizumab is a recombinant humanized VEGF monoclonal antibody, competitively binding to endogenous VEGF receptor. Bevacizumab can inhibit new blood vessel formation, reduce vascular permeability, prevent pleural effusion accumulation and slow the growth of cancers. This review aims to discuss the progress of bevacizumab in the treatment of MPE caused by non-small cell lung cancer(NSCLC), and explore the clinical application, efficacy, safety and future direction of bevacizumab.
引文
1 Uddin A, Chakraborty S. Role of miRNAs in lung cancer. J Cell Physiol, 2018. doi:10.1002/jcp.26607
2 Bradshaw M, Mansfield A, Peikert T. The role of vascular endothelial growth factor in the pathogenesis, diagnosis andtreatment of malignant pleural effusion. Curr Oncol Rep, 2013,15(3):207-216. doi:10.1007/s11912-013-0315-7
3 Keeratichananont W, Limthon T, Keeratichananont S. Efficacy and safety profile of autologous blood versus tetracycline pleurodesis for malignant pleural effusion. Ther Adv Respir Dis, 2015, 9(2):42-48. doi:10.1177/1753465815570307
4 Usuia K, Sugawarab S, Nishitsujic M, et al. A phaseⅡstudy of bevacizumab with carboplatin-pemetrexed in non-squamous non-small cell lung carcinoma patients with malignant pleural effusions:North East Japan Study Group Trial NEJ013A. Lung cancer, 2016, 99:131-136. doi:10.1016/j.lungcan.2016.07.003
5 Coenraad FN K, Jane AS, Elvis MI, et al. Contemporary best practice in the management of malignant pleural effusion. Ther Adv Respir Dis, 2018, 12:1-13. doi:10.1177/1753466618785098
6 Chen Y, Nicholas WM, Lu HD. The role of VEGF in the diagnosis and treatment of malignant pleural effusion in patients with nonsmall cell lung cancer(Review). Mol Med Rep, 2018, 17(6):8019-8030. doi:10.3892/mmr.2018.8922
7 David O B. Vascular endothelial growth factors and vascular permeability. Cardiovasc Res, 2010, 87(2):262-271. doi:10.1093/cvr/cvq105
8 Chinese society of respiratory medicine lung cancer group.Consensus of Chinese experts on anti-angiogenic drug therapy for advanced non-small cell lung cancer(2016 edition). Zhongguo Jie He He Hu Xi Za Zhi, 2016, 39(11):839-849.[中华医学会呼吸病学分会肺癌学组.晚期非小细胞肺癌抗血管生成药物治疗中国呼吸领域专家共识(2016年版).中国结核和呼吸杂志,2016,39(11):839-849.] doi:10.3760/ma.j.issn.1001-0939.2016.11.004
9 Chi J, Bai YJ, Chen H. Clinical trial of bevacizumab combined with carboplatin in the treatment of non-small cell lung cancer with malignant pleural effusion, Zhongguo Lin Chuang Yao Li Xue Za Zhi, 2016, 32(13):1175-1181.[迟晶,白阳,陈虹.贝伐单抗联合卡铂治疗非小细胞肺癌恶性胸腔积液的临床研究.中国临床药理学杂志,2016, 32(13):1175-1181.] doi:10.13699/j.cnki.1001-6821.2016.13.007
10 Han N, Zhang MX, Yu SY, et al. Efficacy of bevacizumab in combination with cisplation and pemetrexed in treatment of malignant plerual effusion in patients with non-squamous nonsmall cell lung cancer. Hua Zhong Ke Ji Da Xue Xue Bao Yi Xue Ban, 2013, 42(5):588-591.[韩娜,张孟贤,于世英,等.贝伐单抗联合顺铂/培美曲塞治疗非鳞癌性非小细胞肺癌恶性胸腔积液的临床研究.华中科技大学学报医学版,2013, 42(5):588-591.]doi:10.3870/j.issn.1672-0741.2013.05.019
11 Tamiya M, Tamiya A, Yamadori T, et al. Phase 2 study of bevacizumab with carboplatin-paclitaxel for non-small cell lung cancer with malignant pleural effusion. Med Oncol, 2013, 30:676.doi:10.1007/s12032-013-0676-7
12 Kitamura K, Kubota K, Ando M, et al. Bevacizumab plus chemotherapy for advanced non-squamous non-smallcell lung cancer with malignant pleural effusion. CancerChemother Pharmacol, 2013, 71(2):457-461. doi:10.1007/S00280-012-2026-4
13 Masago K, Fujimoto D, Fujita S, et al. Response to bevacizumab combination chemotherapy of malignant pleural effusions associated with non-squamous non-small-cell lung cancer. Mol Clin Oncol, 2015, 3(2):415-419. doi:10.3892/mco.2014.457
14 Tao H, Meng QY, Li MZ, et al. Outcomes of bevacizumab combined with chemotherapy in lung adenocarcinoma-induced malignant pleural effusion. Thorac Cancer, 2018, 9(2):298-304.doi:10.1111/1759-7714.12582
15 Johnson DH, Fehrenbacher L, Novotny WF, et al. Randomized phaseⅡtrial comparing bevacizumab plus carboplatin and paclitaxel with carboplatin and paclitaxel alone in previously untreated locally advanced or metastatic non-small-cell lung cancer. J Clin Oncol, 2004, 22(11):2184-2191. doi:10.1200/JC0.2004.11.022
16 Reck M, von Pawel J, Zatloukal P, et al. PhaseⅢtrial of cisplatin plus gemcitabine with either placebo or bevacizumab as first-line therapy for nonsquamous non-small-cell lung cancer:AVAil. J Clin Oncol, 2009, 27(8):1227-1234. doi:10.1200/JC0.2007.14.5466
17 Sun L, Ma JT, Zou HW, et al. Efficacy and safety of chemotherapy or tyrosine kinase inhibitors combined with bevacizumab versus chemotherapy or tyrosine kinase inhibitors alone in the treatment of non-small cell lung cancer:a systematic review and metaanalysis. Med Oncol, 2015, 32(2):473. doi:10.1007/s12032-014-0473-y
18 Cao C, Wang JM, Bunjhoo H, et al. Risk profile of bevacizumab in patients with non-small cell lung cancer:a meta-analysis of randomized controlled trials. Acta oncologica, 2012, 51(2):151-156. doi:10.3109/0284186X.2011.631579
19 Zhang T, Yuan SF, Wang ZP, et al. Bevacizumab combined with chemotherapy for advanced non-small cell lung cancer:A metaanalysis. Zhongguo Fei Ai Za Zhi, 2013, 16(2):82-90.[张涛,袁帅飞,王子平,等.贝伐单抗联合化疗治疗非小细胞肺癌meta分析.中国肺癌杂志,2013, 16(2):82-90.] doi:10.3779/j.issn.1009-3419.2013.02.05
20 Avastin(bevacizumab)solution for intmvenous infusion.prescribing information 2015, Genentech Inc.
21 Avastin(bevacizumab)solution for intravenous infusion. summary of product characteristics. 2015, RochePharma AG:Germany.
22 Du N, Li XS, Li F, et al. Intrapleural combination therapy with bevacizumab and cisplatin for non-small cell lung cancer-mediated malignant pleural effusion. Oncol Rep, 2013, 29(6):2332-2340.doi:10.3892/or.2013.2349
23 Kang HR, Jiang J, Du N. Clinical observation of intrapleural or intraperitoneal hyperthermic perfusion plus bevacizumab on malignant pleural or peritoneal effusion. Lin Chuang Zhong Liu Xue Za Zhi, 2014, 19(4):350-353.[康欢荣,蒋建,杜楠.腔内热灌注联合贝伐珠单抗治疗恶性胸腹腔积液的疗效观察.临床肿瘤学杂志,2014, 19(4):350-353.]
24 Qu B, Jiang W, Zhou ZM. Clinical research of intrapleural combination therapy with bevacizumab and cisplatin for non-small cell lung cancer mediated malignant pleural effusion. Zhongguo Yi Ke Da Xue Xue Bao, 2015, 44(7):648-652.[曲博,姜威,周志明.贝伐单抗联合顺铂治疗非小细胞肺癌恶性胸腔积液的临床研究.中国医科大学学报,2015,44(7):648-652.]
25 Chen L, Xia SY. Therapeutic effect and safety of bevacizumab combined with cisplatin on malignant pleural effusion of patients with non-small cell lung cancer. Shanghai Jiao Tong Da Xue Xue Bao Yi Xue Ban, 2015, 35(8):1194-1198.[陈雷,夏书月.贝伐单抗联合顺铂治疗非小细胞肺癌恶性胸腔积液的效果和安全性.上海交通大学学报医学版,2015, 35(8):1194-1198.] doi:11.3969/j.issn.1674-8115.2015.08.020
26 Yan YH. Therapeutic effect of bevacizumab on malignant pleural effusion in patients with lung cancer. Shandong Yi Yao, 2015,55(1):58-59.[严义红.贝伐单抗治疗肺癌患者恶性胸腔积液疗效观察.山东医药,2015, 55(1):58-59.] doi:10.3969/j.issn.1002-266X.2015.01.024
27 Qi N, Li F, Li XS, et al. Combination use of paclitaxel and avastin enhances treatment effect for the NSCLC patients with malignant pleural effusion. Medicine, 2016, 95(47):1-8. doi:10.1097/MD.0000000000005392
28 Lin FH, Su WP, Jin RN. Clinical analysis of bevacizumab combined with cisplatin in treatment of malignant pleural effusion in patients with nonsmall cell lung cancer. Lin Chuang Jun Yi Za Zhi, 2016,44(7):698-700.[林凤华,苏伟平,金润女.贝伐单抗联合顺铂治疗非小细胞肺癌恶性胸腔积液临床研究.临床军医杂志,2016,44(7):698-700.] doi:10.16680/j.1671-3826.2016.07.11
29 Liu HP, Gong CM, Qu L, et al. Efficacy of bevacizumab combined with pemetrexed/cisplatin on treatment of NSCLC patients with MPE. Xi Nan Guo Fang Yi Yao, 2016, 26(12):1448-1450.[刘华平,龚传明,屈磊,等.贝伐单抗联合培美曲塞/顺铂治疗NSCLC恶性胸腔积液的疗效.西南国防医药,2016, 26(12):1448-1450.] doi:10.3969/j.issn.1004-0188.2016.12.029
30 Chen DW, Song XY, Shi F, et al. Greater efficacy of intracavitary infusion of bevacizumab compared to traditional local treatments for patients with malignant cavity serous effusion. Oncotarget,2017, 8(21):35262-35271. doi:10.18632/oncotarget.13064
31 Jiang M, Chi F, Wu R. Clinical research of intrapleural therapy with bevacizumab plus carboplatin in treatment of malignant pleural effusion caused by non-small cell lung cancer. Lin Chuang Fei Ke Za Zhi, 2017, 22(5):813-816.[姜敏,迟峰,吴荣.贝伐单抗联合卡铂治疗非小细胞肺癌恶性胸腔积液的临床研究.临床肺科杂志,2017, 22(5):813-816.] doi:10.3969/j.issn.1009-6663.2017.05.011
32 Xue DF, Zhao XJ. Study on effect of bevacizumab combined with cisplatin on plerual effusion of non-small cell lung cancer.Zhongguo Yi Yao Dao Kan, 2017, 19(4):377-378.[薛丹凤,赵相军.贝伐单抗联合顺铂对非小细胞肺癌胸腔积液的治疗作用研究.中国医药导刊,2017, 19(4):377-378.]
33 Zhao JZ, Tang J, Ma JT, et al. Efficacy and safety of combined bevacizumab and carboplatin therapy and bevacizumab monotherapy for the treatment of malignant pleural effusion.Zhongguo Yi Ke Da Xue Xue Bao, 2018, 47(4):289-293.[赵健竹,汤隽,马洁韬,等.贝伐珠单抗联合卡铂与贝伐珠单抗单药治疗恶性胸腔积液的疗效和安全性.中国医科大学学报,2018,47(4):289-293.]
34 Sun ZW, Kong S, Zhao C, et al. Evaluation of efficacy and safety for bevacizumab in treating malignant pleural effusions caused by lung cancer through intrapleural injection. Oncotarget, 2017,8(69):113318-113330.
35 Chen DW, Song XY, Zhang Y, et al. Optimizing intrapleural bevacizumab dosing in non-small-cell lung cancer-mediated malignant pleural effusion less is more. Future Oncol, 2018. doi:10.2217/fon-2018-0089
36 Li YL, Liang H, Jiang YH, et al. Efficacy of bevacizumab combined with chemotherapy for malignant pleural effusion in patients with non-small cell lung cancer. Zhong Guo Zhong Liu Lin Chuang Yu Kang Fu, 2018, 25(2):150-152.[李彦磊,梁华,姜玉华,等.贝伐单抗联合化疗在非小细胞肺癌恶性胸腔积液患者中的应用效果.中国肿瘤临床与康复,2018, 25(2):150-152.] doi:10.13455/j.cnki.cjcor.2018.02.07
37 Sun ZJ, Du N, Qi N, et al. Efficacy of intrapleural gemcitabine combined with bevacizumab in treatment of malignant pleural effusions. Jie Fang Jun Yi Xue Yuan Xue Bao, 2018, 39(4):275-278.[孙志佳,杜楠,祁楠,等.胸腔灌注吉西他滨联合贝伐珠单抗治疗恶性胸腔积液的疗效分析.解放军医学院学报,2018, 39(4):275-278.] doi:10.3969/j.issn.2095-5227.2018.04.002
2 Bradshaw M, Mansfield A, Peikert T. The role of vascular endothelial growth factor in the pathogenesis, diagnosis andtreatment of malignant pleural effusion. Curr Oncol Rep, 2013,15(3):207-216. doi:10.1007/s11912-013-0315-7
3 Keeratichananont W, Limthon T, Keeratichananont S. Efficacy and safety profile of autologous blood versus tetracycline pleurodesis for malignant pleural effusion. Ther Adv Respir Dis, 2015, 9(2):42-48. doi:10.1177/1753465815570307
4 Usuia K, Sugawarab S, Nishitsujic M, et al. A phaseⅡstudy of bevacizumab with carboplatin-pemetrexed in non-squamous non-small cell lung carcinoma patients with malignant pleural effusions:North East Japan Study Group Trial NEJ013A. Lung cancer, 2016, 99:131-136. doi:10.1016/j.lungcan.2016.07.003
5 Coenraad FN K, Jane AS, Elvis MI, et al. Contemporary best practice in the management of malignant pleural effusion. Ther Adv Respir Dis, 2018, 12:1-13. doi:10.1177/1753466618785098
6 Chen Y, Nicholas WM, Lu HD. The role of VEGF in the diagnosis and treatment of malignant pleural effusion in patients with nonsmall cell lung cancer(Review). Mol Med Rep, 2018, 17(6):8019-8030. doi:10.3892/mmr.2018.8922
7 David O B. Vascular endothelial growth factors and vascular permeability. Cardiovasc Res, 2010, 87(2):262-271. doi:10.1093/cvr/cvq105
8 Chinese society of respiratory medicine lung cancer group.Consensus of Chinese experts on anti-angiogenic drug therapy for advanced non-small cell lung cancer(2016 edition). Zhongguo Jie He He Hu Xi Za Zhi, 2016, 39(11):839-849.[中华医学会呼吸病学分会肺癌学组.晚期非小细胞肺癌抗血管生成药物治疗中国呼吸领域专家共识(2016年版).中国结核和呼吸杂志,2016,39(11):839-849.] doi:10.3760/ma.j.issn.1001-0939.2016.11.004
9 Chi J, Bai YJ, Chen H. Clinical trial of bevacizumab combined with carboplatin in the treatment of non-small cell lung cancer with malignant pleural effusion, Zhongguo Lin Chuang Yao Li Xue Za Zhi, 2016, 32(13):1175-1181.[迟晶,白阳,陈虹.贝伐单抗联合卡铂治疗非小细胞肺癌恶性胸腔积液的临床研究.中国临床药理学杂志,2016, 32(13):1175-1181.] doi:10.13699/j.cnki.1001-6821.2016.13.007
10 Han N, Zhang MX, Yu SY, et al. Efficacy of bevacizumab in combination with cisplation and pemetrexed in treatment of malignant plerual effusion in patients with non-squamous nonsmall cell lung cancer. Hua Zhong Ke Ji Da Xue Xue Bao Yi Xue Ban, 2013, 42(5):588-591.[韩娜,张孟贤,于世英,等.贝伐单抗联合顺铂/培美曲塞治疗非鳞癌性非小细胞肺癌恶性胸腔积液的临床研究.华中科技大学学报医学版,2013, 42(5):588-591.]doi:10.3870/j.issn.1672-0741.2013.05.019
11 Tamiya M, Tamiya A, Yamadori T, et al. Phase 2 study of bevacizumab with carboplatin-paclitaxel for non-small cell lung cancer with malignant pleural effusion. Med Oncol, 2013, 30:676.doi:10.1007/s12032-013-0676-7
12 Kitamura K, Kubota K, Ando M, et al. Bevacizumab plus chemotherapy for advanced non-squamous non-smallcell lung cancer with malignant pleural effusion. CancerChemother Pharmacol, 2013, 71(2):457-461. doi:10.1007/S00280-012-2026-4
13 Masago K, Fujimoto D, Fujita S, et al. Response to bevacizumab combination chemotherapy of malignant pleural effusions associated with non-squamous non-small-cell lung cancer. Mol Clin Oncol, 2015, 3(2):415-419. doi:10.3892/mco.2014.457
14 Tao H, Meng QY, Li MZ, et al. Outcomes of bevacizumab combined with chemotherapy in lung adenocarcinoma-induced malignant pleural effusion. Thorac Cancer, 2018, 9(2):298-304.doi:10.1111/1759-7714.12582
15 Johnson DH, Fehrenbacher L, Novotny WF, et al. Randomized phaseⅡtrial comparing bevacizumab plus carboplatin and paclitaxel with carboplatin and paclitaxel alone in previously untreated locally advanced or metastatic non-small-cell lung cancer. J Clin Oncol, 2004, 22(11):2184-2191. doi:10.1200/JC0.2004.11.022
16 Reck M, von Pawel J, Zatloukal P, et al. PhaseⅢtrial of cisplatin plus gemcitabine with either placebo or bevacizumab as first-line therapy for nonsquamous non-small-cell lung cancer:AVAil. J Clin Oncol, 2009, 27(8):1227-1234. doi:10.1200/JC0.2007.14.5466
17 Sun L, Ma JT, Zou HW, et al. Efficacy and safety of chemotherapy or tyrosine kinase inhibitors combined with bevacizumab versus chemotherapy or tyrosine kinase inhibitors alone in the treatment of non-small cell lung cancer:a systematic review and metaanalysis. Med Oncol, 2015, 32(2):473. doi:10.1007/s12032-014-0473-y
18 Cao C, Wang JM, Bunjhoo H, et al. Risk profile of bevacizumab in patients with non-small cell lung cancer:a meta-analysis of randomized controlled trials. Acta oncologica, 2012, 51(2):151-156. doi:10.3109/0284186X.2011.631579
19 Zhang T, Yuan SF, Wang ZP, et al. Bevacizumab combined with chemotherapy for advanced non-small cell lung cancer:A metaanalysis. Zhongguo Fei Ai Za Zhi, 2013, 16(2):82-90.[张涛,袁帅飞,王子平,等.贝伐单抗联合化疗治疗非小细胞肺癌meta分析.中国肺癌杂志,2013, 16(2):82-90.] doi:10.3779/j.issn.1009-3419.2013.02.05
20 Avastin(bevacizumab)solution for intmvenous infusion.prescribing information 2015, Genentech Inc.
21 Avastin(bevacizumab)solution for intravenous infusion. summary of product characteristics. 2015, RochePharma AG:Germany.
22 Du N, Li XS, Li F, et al. Intrapleural combination therapy with bevacizumab and cisplatin for non-small cell lung cancer-mediated malignant pleural effusion. Oncol Rep, 2013, 29(6):2332-2340.doi:10.3892/or.2013.2349
23 Kang HR, Jiang J, Du N. Clinical observation of intrapleural or intraperitoneal hyperthermic perfusion plus bevacizumab on malignant pleural or peritoneal effusion. Lin Chuang Zhong Liu Xue Za Zhi, 2014, 19(4):350-353.[康欢荣,蒋建,杜楠.腔内热灌注联合贝伐珠单抗治疗恶性胸腹腔积液的疗效观察.临床肿瘤学杂志,2014, 19(4):350-353.]
24 Qu B, Jiang W, Zhou ZM. Clinical research of intrapleural combination therapy with bevacizumab and cisplatin for non-small cell lung cancer mediated malignant pleural effusion. Zhongguo Yi Ke Da Xue Xue Bao, 2015, 44(7):648-652.[曲博,姜威,周志明.贝伐单抗联合顺铂治疗非小细胞肺癌恶性胸腔积液的临床研究.中国医科大学学报,2015,44(7):648-652.]
25 Chen L, Xia SY. Therapeutic effect and safety of bevacizumab combined with cisplatin on malignant pleural effusion of patients with non-small cell lung cancer. Shanghai Jiao Tong Da Xue Xue Bao Yi Xue Ban, 2015, 35(8):1194-1198.[陈雷,夏书月.贝伐单抗联合顺铂治疗非小细胞肺癌恶性胸腔积液的效果和安全性.上海交通大学学报医学版,2015, 35(8):1194-1198.] doi:11.3969/j.issn.1674-8115.2015.08.020
26 Yan YH. Therapeutic effect of bevacizumab on malignant pleural effusion in patients with lung cancer. Shandong Yi Yao, 2015,55(1):58-59.[严义红.贝伐单抗治疗肺癌患者恶性胸腔积液疗效观察.山东医药,2015, 55(1):58-59.] doi:10.3969/j.issn.1002-266X.2015.01.024
27 Qi N, Li F, Li XS, et al. Combination use of paclitaxel and avastin enhances treatment effect for the NSCLC patients with malignant pleural effusion. Medicine, 2016, 95(47):1-8. doi:10.1097/MD.0000000000005392
28 Lin FH, Su WP, Jin RN. Clinical analysis of bevacizumab combined with cisplatin in treatment of malignant pleural effusion in patients with nonsmall cell lung cancer. Lin Chuang Jun Yi Za Zhi, 2016,44(7):698-700.[林凤华,苏伟平,金润女.贝伐单抗联合顺铂治疗非小细胞肺癌恶性胸腔积液临床研究.临床军医杂志,2016,44(7):698-700.] doi:10.16680/j.1671-3826.2016.07.11
29 Liu HP, Gong CM, Qu L, et al. Efficacy of bevacizumab combined with pemetrexed/cisplatin on treatment of NSCLC patients with MPE. Xi Nan Guo Fang Yi Yao, 2016, 26(12):1448-1450.[刘华平,龚传明,屈磊,等.贝伐单抗联合培美曲塞/顺铂治疗NSCLC恶性胸腔积液的疗效.西南国防医药,2016, 26(12):1448-1450.] doi:10.3969/j.issn.1004-0188.2016.12.029
30 Chen DW, Song XY, Shi F, et al. Greater efficacy of intracavitary infusion of bevacizumab compared to traditional local treatments for patients with malignant cavity serous effusion. Oncotarget,2017, 8(21):35262-35271. doi:10.18632/oncotarget.13064
31 Jiang M, Chi F, Wu R. Clinical research of intrapleural therapy with bevacizumab plus carboplatin in treatment of malignant pleural effusion caused by non-small cell lung cancer. Lin Chuang Fei Ke Za Zhi, 2017, 22(5):813-816.[姜敏,迟峰,吴荣.贝伐单抗联合卡铂治疗非小细胞肺癌恶性胸腔积液的临床研究.临床肺科杂志,2017, 22(5):813-816.] doi:10.3969/j.issn.1009-6663.2017.05.011
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