降低曲妥珠单抗使用时间对HER-2阳性乳腺癌患者影响的系统评价
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摘要
目的:系统评价降低曲妥珠单抗使用时间对人类表皮生长因子受体2(HER-2)阳性乳腺癌患者的影响。方法:计算机检索PubMed、Embase、the Cochrane Library(2018年5期)、Clinicaltrial. gov、Sino Med、CNKI、Wan-Fang Data和VIP数据库,搜集曲妥珠单抗不同给药疗程治疗HER-2阳性乳腺癌患者的随机对照试验(RCTs),检索时限均为建库至2018年5月。由两位研究人员独立进行文献筛选、数据提取和偏倚风险评价后,采用RevMan 5. 3软件进行Meta分析。结果:共纳入4个RCTs,包括9 466例患者,Meta分析结果显示,与对照组(6个月组)相比,试验组(12个月组)因心脏毒性提前停药[Peto OR=2. 49,95%CI(1. 83,3. 39),P <0. 000 01]、心功能障碍[Peto OR=1. 50,95%CI(1. 23,1. 83),P <0. 000 1]、LVEF <50%[Peto OR=1. 39,95%CI(1. 14,1. 70),P=0. 001]的发生率更高,差异有统计学意义。两组在有效率与死亡率方面的差异无统计学意义(P> 0. 05)。结论:当前证据表明,缩短曲妥珠单抗的使用时间,并未降低治疗效果,但却可以降低心脏毒性。受纳入研究数量和质量的影响,上述结论尚需大样本高质量临床研究予以证实。
Objective: To systematically evaluate the effect of reducing trastuzumab use time on HER-2 positive breast cancer patients. Methods: PubMed,EMBase,The Cochrane Library( Issue 5,2018),Clinicaltrial. gov,Sino Med,CNKI,Wan Fang Data and VIP databases were electronically searched to collect randomized controlled trials( RCTs) of reducing trastuzumab use time on HER-2 positive breast cancer patients from inception to May 2018. Two reviewers independently screened literatures,extracted data and assessed risk of bias of included studies. Then Meta-analysis was performed by RevMan 5. 3 software. Results: A total of 4 RCTs involving 9 466 patients were included. The results of Meta-analysis showed that: compared with control group( 6 months group),the early cardiac discontinuation due to cardiotoxicity( Peto OR = 2. 49,95% CI 1. 83 to 3. 39,P < 0. 000 01),the cardiac function obstacle( Peto OR = 1. 50,95% CI 1. 23 to1. 83,P < 0. 000 1),LVEF < 50%( Peto OR = 1. 39,95% CI 1. 14 to 1. 70,P = 0. 001) of experimental group( 12 months group) was higher,the difference was statistically significant. There was no significant difference between the two groups in the efficiency and mortality rate( P > 0. 05). Conclusion: Current evidence showed that shortening the use of trastuzumab didn't reduce the effect,but it could reduce cardiotoxicity. Due to the limited quality of included studies,the above conclusion still needed to be verified by more high quality studies.
Objective: To systematically evaluate the effect of reducing trastuzumab use time on HER-2 positive breast cancer patients. Methods: PubMed,EMBase,The Cochrane Library( Issue 5,2018),Clinicaltrial. gov,Sino Med,CNKI,Wan Fang Data and VIP databases were electronically searched to collect randomized controlled trials( RCTs) of reducing trastuzumab use time on HER-2 positive breast cancer patients from inception to May 2018. Two reviewers independently screened literatures,extracted data and assessed risk of bias of included studies. Then Meta-analysis was performed by RevMan 5. 3 software. Results: A total of 4 RCTs involving 9 466 patients were included. The results of Meta-analysis showed that: compared with control group( 6 months group),the early cardiac discontinuation due to cardiotoxicity( Peto OR = 2. 49,95% CI 1. 83 to 3. 39,P < 0. 000 01),the cardiac function obstacle( Peto OR = 1. 50,95% CI 1. 23 to1. 83,P < 0. 000 1),LVEF < 50%( Peto OR = 1. 39,95% CI 1. 14 to 1. 70,P = 0. 001) of experimental group( 12 months group) was higher,the difference was statistically significant. There was no significant difference between the two groups in the efficiency and mortality rate( P > 0. 05). Conclusion: Current evidence showed that shortening the use of trastuzumab didn't reduce the effect,but it could reduce cardiotoxicity. Due to the limited quality of included studies,the above conclusion still needed to be verified by more high quality studies.
引文
1世界卫生组织.癌症实况报道[EB/OL].(2017-02)[2018-07-01]http:∥www. who. int/mediacentre/factsheets/fs297/zh/
2 黄哲宙,陈万青,吴春晓,等.中国女性乳腺癌的发病和死亡现况——全国32个肿瘤登记点2003~2007年资料分析报告[J].肿瘤,2012,32(6):435-439
3 Piccart-Gebhart MJ,Procter M,Leyland-Jones B,et al.Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer[J]. N Engl J Med,2005,353(16):1659-1672
4 Romond EH,Perez EA,Bryant J,et al. Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer[J]. N Engl J Med,2005,353(16):1673-1684
5 Slamon D,Eiermann W,Robert N,et al. Adjuvant trastuzumab in HER2-positive breast cancer[J]. N Engl J Med,2011,365(14):1273-1283
6 Joensuu H,Kellokumpu-Lehtinen PL,Bono P,et al. Adjuvant docetaxel or vinorelbine with or without trastuzumab for breast cancer[J]. N Engl J Med,2006,354(8):809-820
7 Gradishar WJ,Anderson BO,Balassanian R,et al. NCCN guidelines insights:breast cancer,version 1. 2017[J]. J Natl Compr Canc Netw,2017,15(4):433-451
8 William WN Jr,Pataer A,Kalhor N,et al. Computed tomography RECIST assessment of histopathologic response and prediction of survival in patients with resectable non-smallcell lung cancer after neoadjuvant chemotherapy[J]. J Thorac Oncol,2013,8(2):222-228
9 Higgins JP,Green S. Cochrane Handbook for Systematic Reviews of Interventions(Version 5. 1. 0)[EB/OL].(2012-01-05)[2018-07-01]http:∥www. cochrane-handbook. org
10 Earl HM,Vallier AL,Dunn J,et al. Trastuzumab-associated cardiac events in the Persephone trial[J]. Br J Cancer,2016,115(12):1462-1470
11 Mavroudis D,Saloustros E,Malamos N,et al. Six versus 12 months of adjuvant trastuzumab in combination with dosedense chemotherapy for women with HER2-positive breast cancer:a multicenter randomized study by the Hellenic Oncology Research Group(HORG)[J]. Ann Oncol,2015,26(7):1333-1340
12 Pivot X,Romieu G,Debled M,et al. 6 months versus 12months of adjuvant trastuzumab for patients with HER2-positive early breast cancer(PHARE):a randomised phase 3trial[J]. Lancet Oncol,2013,14(8):741-748
13 Goldhirsch A,Gelber RD,Piccart-Gebhart MJ,et al. 2years versus 1 year of adjuvant trastuzumab for HER2-positive breast cancer(HERA):an open-label,randomised controlled trial[J]. Lancet,2013,382(9897):1021-1028
14 Farolfi A,Melegari E,Aquilina M,et al. Trastuzumab-induced cardiotoxicity in early breast cancer patients:a retrospective study of possible risk and protective factors[J].Heart,2013,99(9):634-639
15 张丹丹,程文,刘莹,等.超声心动图评价赫塞汀对乳腺癌患者心脏毒性[J].现代肿瘤医学,2013,21(8):1862-1865
16 盛李明,杜向慧.乳腺癌患者赫赛汀相关心脏毒性机制及处理[J].中国临床药理学与治疗学,2011,16(9):1077-1080
17 李晓玲,王育琴.曲妥珠单抗心脏毒性及防治策略[J].药物不良反应杂志,2009,11(4):257-263
18 Babar T,Blomberg C,Hoffner E,et al. Anti-HER2 cancer therapy and cardiotoxicity[J]. Curr Pharm Des,2014,20(30):4911-4919
2 黄哲宙,陈万青,吴春晓,等.中国女性乳腺癌的发病和死亡现况——全国32个肿瘤登记点2003~2007年资料分析报告[J].肿瘤,2012,32(6):435-439
3 Piccart-Gebhart MJ,Procter M,Leyland-Jones B,et al.Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer[J]. N Engl J Med,2005,353(16):1659-1672
4 Romond EH,Perez EA,Bryant J,et al. Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer[J]. N Engl J Med,2005,353(16):1673-1684
5 Slamon D,Eiermann W,Robert N,et al. Adjuvant trastuzumab in HER2-positive breast cancer[J]. N Engl J Med,2011,365(14):1273-1283
6 Joensuu H,Kellokumpu-Lehtinen PL,Bono P,et al. Adjuvant docetaxel or vinorelbine with or without trastuzumab for breast cancer[J]. N Engl J Med,2006,354(8):809-820
7 Gradishar WJ,Anderson BO,Balassanian R,et al. NCCN guidelines insights:breast cancer,version 1. 2017[J]. J Natl Compr Canc Netw,2017,15(4):433-451
8 William WN Jr,Pataer A,Kalhor N,et al. Computed tomography RECIST assessment of histopathologic response and prediction of survival in patients with resectable non-smallcell lung cancer after neoadjuvant chemotherapy[J]. J Thorac Oncol,2013,8(2):222-228
9 Higgins JP,Green S. Cochrane Handbook for Systematic Reviews of Interventions(Version 5. 1. 0)[EB/OL].(2012-01-05)[2018-07-01]http:∥www. cochrane-handbook. org
10 Earl HM,Vallier AL,Dunn J,et al. Trastuzumab-associated cardiac events in the Persephone trial[J]. Br J Cancer,2016,115(12):1462-1470
11 Mavroudis D,Saloustros E,Malamos N,et al. Six versus 12 months of adjuvant trastuzumab in combination with dosedense chemotherapy for women with HER2-positive breast cancer:a multicenter randomized study by the Hellenic Oncology Research Group(HORG)[J]. Ann Oncol,2015,26(7):1333-1340
12 Pivot X,Romieu G,Debled M,et al. 6 months versus 12months of adjuvant trastuzumab for patients with HER2-positive early breast cancer(PHARE):a randomised phase 3trial[J]. Lancet Oncol,2013,14(8):741-748
13 Goldhirsch A,Gelber RD,Piccart-Gebhart MJ,et al. 2years versus 1 year of adjuvant trastuzumab for HER2-positive breast cancer(HERA):an open-label,randomised controlled trial[J]. Lancet,2013,382(9897):1021-1028
14 Farolfi A,Melegari E,Aquilina M,et al. Trastuzumab-induced cardiotoxicity in early breast cancer patients:a retrospective study of possible risk and protective factors[J].Heart,2013,99(9):634-639
15 张丹丹,程文,刘莹,等.超声心动图评价赫塞汀对乳腺癌患者心脏毒性[J].现代肿瘤医学,2013,21(8):1862-1865
16 盛李明,杜向慧.乳腺癌患者赫赛汀相关心脏毒性机制及处理[J].中国临床药理学与治疗学,2011,16(9):1077-1080
17 李晓玲,王育琴.曲妥珠单抗心脏毒性及防治策略[J].药物不良反应杂志,2009,11(4):257-263
18 Babar T,Blomberg C,Hoffner E,et al. Anti-HER2 cancer therapy and cardiotoxicity[J]. Curr Pharm Des,2014,20(30):4911-4919