参一胶囊联合化疗治疗晚期非小细胞肺癌疗效观察与血清MMP-9及TIMP-1变化

The study of serum matrix metalloproteinase- 9 and its inhibitor and the efficacy of Shenyi capsule combined with chemotherapy in the treatment of advanced NSCLC

目的:探讨参一胶囊联合一线化疗方案与单独化疗治疗不能手术的晚期IIIb/Ⅳ初治非小细胞肺癌(NSCLC)患者血清基质金属蛋白酶9(MMP-9)及组织蛋白酶抑制剂-1(TIMP-1)水平变化,并观察其近期疗效和治疗后不良反应。方法:采用酶联免疫吸附法(ELISA)检测89例肺癌患者化疗前后血浆MMP-9及TIMP-1水平。结果:两组有效率无显著性差异(P>0.05),两组疾控率比较差异有显著性(P<0.05)。全部CR+PR、SD、PD患者治疗前血清MMP-9、TIMP-1水平比较,无显著性差异(P>0.05),治疗后差异均具有有显著性(P<0.05),随疗效降低呈升高趋势。两组相比疗前与疗后两次血清MMP-9水平,参一联合化疗组下降更明显,差异有显著性(P<0.05),而血清TIMP-1水平差异无显著性(P>0.05)。IV期患者比IIIb期患者外周血清MMP-9水平明显增高,差异有显著性(P<0.05)。但外周血清TIMP-1在IIIb期和IV期无统计学差异。其他因素如年龄、性别、ECOG评分、病理与MMP-9、TIMP-1水平均未发现显著性差异。患者治疗后出现常见不良反应及生活质量(quality of life,QOL)观察:观察组(即参一胶囊联合化疗组)在胃肠道反应(如恶心、呕吐、腹胀等),骨髓抑制(如白细胞减少、贫血、血小板下降等)方面均较单独化疗组减轻(P<0.05),参一联合组在改善QOL方面也明显高于对照组,且有统计学差异(P<0.05)。结论:参一胶囊联合化疗组患者外周血清MMP-9水平下降更明显,且有统计学差异,而患者血清TIMP-1水平变化无统计学差异。血清MMP-9、TIMP-1水平治疗后随疗效降低呈升高趋势,因此,两者对患者疗效判定具有一定的参考价值。两组外周血清MMP-9、TIMP-1水平变化不受性别、年龄、ECOG评分影响。肺癌患者TNM分期对NSCLC患者外周血清MMP-9水平变化有影响,分期越晚,其外周血清MMP-9水平值越高。因此,MMP-9血清值越高,提示预后越差。外周血清TIMP-1水平与MMP-9水平在化疗前后NSCLC患者呈正相关。参一胶囊对非小细胞肺癌患者可以增加疗效,减少毒副反应,生活质量得到提高,不良反应如消化道症状及骨髓抑制均可以减轻。

Objective： To study Shenyi capsule combined with chemotherapy and chemotherapy alone on advanced IIIb/ IV non small cell lung cancer（ NSCLC） and effect on serum MMP- 9 and TIMP- 1 levels. Methods： Patients were randomly assigned to Shenyi capsule plus chemotherapy group and chemotherapy group. Chemotherapy include：Pacilitaxel 175 mg / m^2,ivdrip d1,Cisplatin 75mg/m^2,ivdrip divided into 3 or 4 days for a period of 21 days,Pemetrexed 500 mg / m^2,ivdrip dl,Cisplatin 75mg/m^2,ivdrip divided into 3 or 4 days with a 21- day cycle,Gemcitabine 1 000 mg / m^2,ivdrip d1,8,Cisplatin 75mg/m^2,ivdrip divided into 3 or 4 days with a 21- day cycle,NP（ Vinorelbine 25 mg / m^2,ivdrip d1,8,Cisplatin 75mg/m^2,ivdrip divided into 3 or 4 days with a 21- day cycle）. Shenyi capsule each oral 20 mg,bid,at least 6 weeks. To detect serum MMP- 9 and TIMP- 1 level before chemotherapy and after the two course of chemotherapy using ELISA method. Results： Total of 45 patients in Shenyi capsule group,44 cases in hemotherapy group. The two groups did not appear completely remission. Capsule plus chemotherapy group,PR 20（ 44. 4%）,SD 17（ 37. 8%）,PD 8（ 17. 8%） with RR 20（ 44. 4%） and clinical benefit 82. 2%,in chemotherapy group,PR 16（ 36. 4%）,SD 11（ 25. 0%）,PD 17（ 38. 6%） with RR 1 6（ 3 6. 4 %） and clinical benefit 61. 4%（ P〈0. 05）. Disease control had a significant difference（ P〈0. 05）. Comparison of CR ＋ PR,SD,PD in all patients before treatment,serum MMP- 9,TIMP- 1 levels,there was no significant difference（ P〉0. 05）. After treatment,there was a significant difference（ P〈0. 05）,an increasing trend with the effect lowering. Compared two groups before treatment and after treatment two times the level of serum MMP- 9,Shenyi capsule and a combined chemotherapy group decreased more significantly,the difference was significant（ P〈0. 05）,while no significant difference of serum TIMP- 1 level（ P〉0. 05）. The relationship between patients with other features and MMP- 9,TIMP- 1 levels： the levels of MMP- 9 in patients with stage IV than patients with stage IIIbin peripheral blood were significantly increased,the difference was significant（ P〈0. 05）. But the peripheral serum TIMP- 1 in IIIb phase and IV phase had no significant difference. Age,gender,ECOG,pathology,significant differences were not found in MMP- 9,TIMP- 1levels. Common side effects and QOL（ quality of life,QOL） observation： the observation group（ Shenyi capsule combined with chemotherapy group） in the gastrointestinal tract reaction（ such as nausea,vomiting,abdominal distension）,bone marrow suppression（ such as leukopenia,anemia,thrombocytopenia） were lower than control group reduce（ P〈0. 05）,the observation group in improving the quality of life was also significantly higher than that of the control group（ P〈0. 05）. Conclusion： Shenyi capsule combined with chemotherapy peripheral serum MMP- 9 level decreased more significantly,and there is significant difference,but there is no significant difference between the changes of serum TIMP- 1 level. Serum MMP- 9,TIMP- 1 levels after treatment with reduced efficacy showed a rising trend,therefore it can be used as a reference index to judge the curative effect.