贝伐单抗联合紫杉醇和顺铂治疗非小细胞肺癌的疗效及对microRNA-99a、miRNA-145的影响
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摘要
目的评估贝伐单抗联合紫杉醇和顺铂治疗非小细胞肺癌的疗效,探讨其对microRNA-99a、miRNA-145的影响。方法我院于2015年1月至2017年1月期间收治的120例NSCLC患者,依据随机数字表法分为两组,观察组(n=60)采用贝伐单抗联合紫杉醇和顺铂治疗,对照组(n=60)采用紫杉醇和顺铂治疗,每个疗程28d,共治疗4个疗程。比较两组患者疗效及microRNA-99a、miRNA-145变化。结果观察组治疗总有效率(78.3%)显著高于对照组(53.3%)(χ~2=8.336,P=0.004);观察组治疗前microRNA-99a、miRNA-145水平分别为(8.84±2.02)×10~(-6)、(0.92±0.28),治疗后显著升高至(42.23±15.43)×10~(-6)、(1.85±0.30)(P<0.05),对照组治疗前为(8.70±2.13)×10~(-6)、(0.83±0.25),治疗后升至(18.74±14.17)×10~(-6)、(1.22±0.28)(P<0.05),观察组治疗后的血清microRNA-99a、miRNA-145水平显著高于对照组(P<0.05);观察组和对照组不良反应率(13.3%和16.7%)差异无统计学意义(P>0.05)。结论贝伐单抗联合紫杉醇和顺铂治疗非小细胞肺癌显著提高近期疗效,同时促进血清microRNA-99a、miRNA-145的表达,从而降低肿瘤恶性程度。
Objective To explore the clinical efficacy of bevacizumab combined with paclitaxel and cisplatin in treatment of non-small cell lung cancer and its influence on microRNA-99 a and miRNA-145. Methods 120 cases of NSCLC patients from January 2015 to January 2017 were randomly divided into two groups. The observation group( n = 60) was treated with bevacizumab combined with paclitaxel and cisplatin for 4 courses with 28 days of one course,and the control group( n = 60) was treated with paclitaxel and cisplatin for 4 courses. The clinical efficacy and changes of microRNA-99 a and miRNA-145 were compared. Results The total effective rate in the observation group( 78. 3%) was significantly higher than that of the control group( 53. 3%)( χ2= 9. 412,P = 0. 002). The levels of microRNA-99 a and miRNA-145 in the observation group were( 8. 84 ± 2. 02) × 10-6 and( 0. 92 ± 0. 28),and significantly increased to( 42. 23 ± 15. 43) × 10-6 and( 1. 85 ± 0. 30) after treatment( P < 0. 05). In the control group,they were( 8. 70 ± 2. 13) × 10-6 and( 0. 83 ± 0. 25),and significantly increased to( 18. 74 ± 14. 17) ×10-6 and( 1. 22 ± 0. 28) after treatment( P < 0. 05). The levels of serum microRNA-99 a and miRNA-145 in the observation group were significantly higher than that of the control group( P < 0. 05). There was no significant difference in adverse reaction rate between the two groups( 13. 3% and 16. 7%)( P > 0. 05). Conclusion Bevacizumab combined with paclitaxel and cisplatin can improve short-term efficacy in treatment of non-small cell lung cancer,and increase the expression of serum microRNA-99 a and miRNA-145,thereby reducing the degree of tumor malignancy.
Objective To explore the clinical efficacy of bevacizumab combined with paclitaxel and cisplatin in treatment of non-small cell lung cancer and its influence on microRNA-99 a and miRNA-145. Methods 120 cases of NSCLC patients from January 2015 to January 2017 were randomly divided into two groups. The observation group( n = 60) was treated with bevacizumab combined with paclitaxel and cisplatin for 4 courses with 28 days of one course,and the control group( n = 60) was treated with paclitaxel and cisplatin for 4 courses. The clinical efficacy and changes of microRNA-99 a and miRNA-145 were compared. Results The total effective rate in the observation group( 78. 3%) was significantly higher than that of the control group( 53. 3%)( χ2= 9. 412,P = 0. 002). The levels of microRNA-99 a and miRNA-145 in the observation group were( 8. 84 ± 2. 02) × 10-6 and( 0. 92 ± 0. 28),and significantly increased to( 42. 23 ± 15. 43) × 10-6 and( 1. 85 ± 0. 30) after treatment( P < 0. 05). In the control group,they were( 8. 70 ± 2. 13) × 10-6 and( 0. 83 ± 0. 25),and significantly increased to( 18. 74 ± 14. 17) ×10-6 and( 1. 22 ± 0. 28) after treatment( P < 0. 05). The levels of serum microRNA-99 a and miRNA-145 in the observation group were significantly higher than that of the control group( P < 0. 05). There was no significant difference in adverse reaction rate between the two groups( 13. 3% and 16. 7%)( P > 0. 05). Conclusion Bevacizumab combined with paclitaxel and cisplatin can improve short-term efficacy in treatment of non-small cell lung cancer,and increase the expression of serum microRNA-99 a and miRNA-145,thereby reducing the degree of tumor malignancy.
引文
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[9] 李小峰,张亚华.顺铂联合吉西他滨与联合紫杉醇治疗晚期非小细胞肺癌疗效分析[J].现代肿瘤医学,2014,22(5):1087-1089.
[10] 赵卫刚,胡世莲,丁西平,等.吉西他滨联合顺铂与紫杉醇联合顺铂/卡铂治疗非小细胞肺癌疗效的系统评价[J].实用医学杂志,2016,32(9):1508-1511.
[11] 崔洪霞,李玉权,戴继鑫,等.贝伐单抗联合化疗一线治疗晚期非鳞非小细胞癌临床观察[J].当代医学,2013,19(34):1-2.
[12] 毕金玲,刘海渊,丁露,等.白蛋白结合型紫杉醇联合卡铂和贝伐单抗作为非小细胞肺癌一线方案的疗效和安全性研究[J] 中国临床保健杂志,2016,19(6):618-621.
[13] BARLESI F,SCHERPEREEL A,RITTMEYER A,et al.Randomized phase Ⅲ trial of maintenance bevacizumab with or without pemetrexed after first-line induction with bevacizumab, cisplatin, and pemetrexed in advanced nonsquamous non-small-cell lung cancer:AVAPERL (MO22089)[J].J Clin Oncol,2013,31(24):3004-3011.
[14] JOHNSON B E,KABBINAVAR F,FEHRENBACHER L,et al.ATLAS:randomized,double-blind,placebo-controlled,phase ⅢB trial comparing bevacizumab therapy with or without erlotinib, after completion of chemotherapy, with bevacizumab for first-line treatment of advanced non-small-cell lung cancer[J].J Clin Oncol,2013,31(31):3926-3934.
[15] KASINSKI A L,KELNAR K,STAHLHUT C,et al.A combinatorial microRNA therapeutics approach to suppressing non-small cell lung cancer[J].Oncogene,2015,34(27):3547-3555.
[16] YU S H,ZHANG C L,DONG F S,et al.miR‐99a Suppresses the metastasis of human non‐small cell lung cancer cells by targeting AKT1 signaling pathway[J].J Cell Biochem,2015,116(2):268-276.
[17] LI J M,KAO K C,LI L F,et al.MicroRNA-145 regulates oncolytic herpes simplex virus-1 for selective killing of human non-small cell lung cancer cells[J].Virol J,2013,10:241-248.
[18] 张潍,张伟,王辉,等.miRNA-141, miRNA-145 在非小细胞肺癌中的表达及与临床病理的关系[J].西安交通大学学报(医学版),2015,36(3):368-372.
[19] 徐小峰,夏春伟,陈文萍.microRNA-99a在非小细胞肺癌中的表达及临床意义[J].现代肿瘤医学,2014,22(10):2312-2314.
[20] YE Z,SHEN N,WENG Y,et al.Low miR-145 silenced by DNA methylation promotes NSCLC cell proliferation,migration and invasion by targeting mucin 1[J].Cancer Biol Ther,2015,16(7):1071-1079.
[2] BRADLEY J D,PAULUS R,KOMAKI R,et al.Standard-dose versus high-dose conformal radiotherapy with concurrent and consolidation carboplatin plus paclitaxel with or without cetuximab for patients with stage ⅢA or ⅢB non-small-cell lung cancer (RTOG 0617):a randomised,two-by-two factorial phase 3 study[J].Lancet Oncol,2015,16(2):187-199.
[3] SETO T,KATO T,NISHIO M,et al.Erlotinib alone or with bevacizumab as first-line therapy in patients with advanced non-squamous non-small-cell lung cancer harbouring EGFR mutations (JO25567):an open-label,randomised,multicentre,phase 2 study[J].Lancet Oncol,2014,15(11):1236-1244.
[4] PATEL J D,SOCINSKI M A,GARON E B,et al.PointBreak:a randomized phase Ⅲ study of pemetrexed plus carboplatin and bevacizumab followed by maintenance pemetrexed and bevacizumab versus paclitaxel plus carboplatin and bevacizumab followed by maintenance bevacizumab in patients with stage ⅢB or Ⅳ nonsquamous non-small-cell lung cancer[J].J Clin Oncol,2013,31(34):4349-4357.
[5] CHEN C,ZHAO Z,LIU Y,et al.microRNA 99a is downregulated and promotes proliferation, migration and invasion in non-small cell lung cancer A549 and H1299 cells[J].Oncol Lett,2015,9(3):1128-1134.
[6] SHEN H,SHEN J,WANG L,et al.Low miR-145 expression level is associated with poor pathological differentiation and poor prognosis in non-small cell lung cancer[J].Biomed Pharmacother,2015,69(17):301-305.
[7] 张绪超,陆舜,张力,等.中国间变性淋巴瘤激酶(ALK)阳性非小细胞肺癌诊断专家共识(2013版)[S].中华病理学杂志,2013,42(6):402-406.
[8] 杨学宁,吴一龙.实体瘤治疗疗效评价标准—RECIST[J].循证医学,2004,4(2):85-90,111.
[9] 李小峰,张亚华.顺铂联合吉西他滨与联合紫杉醇治疗晚期非小细胞肺癌疗效分析[J].现代肿瘤医学,2014,22(5):1087-1089.
[10] 赵卫刚,胡世莲,丁西平,等.吉西他滨联合顺铂与紫杉醇联合顺铂/卡铂治疗非小细胞肺癌疗效的系统评价[J].实用医学杂志,2016,32(9):1508-1511.
[11] 崔洪霞,李玉权,戴继鑫,等.贝伐单抗联合化疗一线治疗晚期非鳞非小细胞癌临床观察[J].当代医学,2013,19(34):1-2.
[12] 毕金玲,刘海渊,丁露,等.白蛋白结合型紫杉醇联合卡铂和贝伐单抗作为非小细胞肺癌一线方案的疗效和安全性研究[J] 中国临床保健杂志,2016,19(6):618-621.
[13] BARLESI F,SCHERPEREEL A,RITTMEYER A,et al.Randomized phase Ⅲ trial of maintenance bevacizumab with or without pemetrexed after first-line induction with bevacizumab, cisplatin, and pemetrexed in advanced nonsquamous non-small-cell lung cancer:AVAPERL (MO22089)[J].J Clin Oncol,2013,31(24):3004-3011.
[14] JOHNSON B E,KABBINAVAR F,FEHRENBACHER L,et al.ATLAS:randomized,double-blind,placebo-controlled,phase ⅢB trial comparing bevacizumab therapy with or without erlotinib, after completion of chemotherapy, with bevacizumab for first-line treatment of advanced non-small-cell lung cancer[J].J Clin Oncol,2013,31(31):3926-3934.
[15] KASINSKI A L,KELNAR K,STAHLHUT C,et al.A combinatorial microRNA therapeutics approach to suppressing non-small cell lung cancer[J].Oncogene,2015,34(27):3547-3555.
[16] YU S H,ZHANG C L,DONG F S,et al.miR‐99a Suppresses the metastasis of human non‐small cell lung cancer cells by targeting AKT1 signaling pathway[J].J Cell Biochem,2015,116(2):268-276.
[17] LI J M,KAO K C,LI L F,et al.MicroRNA-145 regulates oncolytic herpes simplex virus-1 for selective killing of human non-small cell lung cancer cells[J].Virol J,2013,10:241-248.
[18] 张潍,张伟,王辉,等.miRNA-141, miRNA-145 在非小细胞肺癌中的表达及与临床病理的关系[J].西安交通大学学报(医学版),2015,36(3):368-372.
[19] 徐小峰,夏春伟,陈文萍.microRNA-99a在非小细胞肺癌中的表达及临床意义[J].现代肿瘤医学,2014,22(10):2312-2314.
[20] YE Z,SHEN N,WENG Y,et al.Low miR-145 silenced by DNA methylation promotes NSCLC cell proliferation,migration and invasion by targeting mucin 1[J].Cancer Biol Ther,2015,16(7):1071-1079.