黄芪解毒汤联合GT化疗方案治疗转移性三阴性乳腺癌疗效及对患者Th1/Th2细胞因子平衡的影响
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摘要
目的探讨转移性三阴性乳腺癌(mTNBC)应用黄芪解毒汤联合GT化疗方案治疗的临床效果。方法选取2017年1月-2018年3月我院收治的102例mTNBC女性患者,按照随机数字表法分为观察组(51例)与对照组(51例)。对照组采取GT化疗方案(吉西他滨+紫杉醇)治疗,观察组在对照组的基础上联合黄芪解毒汤口服,所有患者均治疗6个周期。比较两组患者的临床疗效、治疗前后证候总积分、血清肿瘤标志物[癌胚抗原(CEA)、糖类抗原15-3(CA15-3)]和辅助性T细胞Th1/Th2细胞因子[白介素2(IL-2)、γ干扰素(IFN-γ)、IL-6]水平、毒副反应发生情况。结果观察组客观缓解率(ORR)为45.1%(23/51),对照组为29.4%(15/51),差异无统计学意义(P>0.05);观察组临床获益率(CBR)为78.4%(40/51),对照组为58.8%(30/51),差异有统计学意义(P<0.05)。与治疗前相比,两组治疗后证候总积分及血清CEA、CA15-3水平均显著降低(P<0.05),且观察组显著低于对照组(P<0.05)。两组治疗后血清IL-2、IFN-γ水平及IL-2/IL-6、IFN-γ/IL-6比值均较治疗前显著增加(P<0.05),IL-6水平较治疗前显著下降(P<0.05),且观察组改善更为显著(P<0.05)。观察组Ⅲ-Ⅳ级毒副反应发生率为15.7%(8/51),对照组为33.3%(17/51),差异有统计学意义(P<0.05)。结论应用黄芪解毒汤联合GT化疗方案治疗mTNBC可明显缓解患者正虚毒炽相关症状,控制肿瘤进展,纠正Th1/Th2细胞因子平衡的病理性偏移,减轻化疗毒副反应,具有显著的减毒增效优势。
Objective To explore clinical effect of Huangqi Jiedu decoction combined with GT chemotherapy in the treatment of metastatic triple-negative breast cancer(mTNBC). Methods Selected 102 cases with mTNBC in our hospital from January 2017 to March 2018 as research objectives, and divided them into observation group(n=51) and control group(n=51) randomly. Both groups had gemcitabine +paclitaxel(GT chemotherapy), but observation group had oral Huangqi Jiedu decoction additionally. All received chemotherapy for 6 months.Compared clinical effects, total scores of symptoms, levels of serum tumor markers such as carcinoembryonic antigen(CEA) and carbohydrate antigen 15-3(CA15-3), and levels of helper T cells Th1/Th2 cytokines like interleukin-6(IL-2), interferon-γ(IFN-γ), IL-6 before and after treatments, as well as toxic side effects between the two groups. Results The objective response rate(ORR) was 45.1%(23/51)in the observation group, higher than that of control group [29.4%(15/51) ], but the difference was not statistically significant(P>0.05).However, the clinical benefit rate(CBR) of the observation group was significantly higher than that of the control group [78.4%(40/51)vs.58.8%(30/51), P<0.05]. Compared with before treatment, the total scores of symptoms and levels of serum CEA and CA15-3 decreased significantly in both groups after treatment(P<0.05), and even decreased greater in observation group than in control group(P<0.05). The serum levels of IL-2 and IFN-γ and the ratios of IL-2/IL-6 and IFN-γ/IL-6 were significant higher than those before treatment(P<0.05),while the IL-6 level decreased(P<0.05). Moreover, such improvement were found greater in observation group than in control group(P<0.05). Besides, the incidence of toxic and side effects was significantly lower in observation group than in control group [15.7%(8/51)vs.33.3%(17/51), P<0.05]. Conclusion Huangqi Jiedu decoction combined with GT chemotherapy helps mTNBC patients to alleviate the symptoms relevant with weakened body resistance and poison flourishing. It could control tumor progression, correct pathological shift of Th1/Th2 cytokine balance and reduce the side effects of chemotherapy. Consequently, Huangqi Jiedu decoction shows significant advantages in reducing toxicity and enhancing efficacy of chemotherapy.
Objective To explore clinical effect of Huangqi Jiedu decoction combined with GT chemotherapy in the treatment of metastatic triple-negative breast cancer(mTNBC). Methods Selected 102 cases with mTNBC in our hospital from January 2017 to March 2018 as research objectives, and divided them into observation group(n=51) and control group(n=51) randomly. Both groups had gemcitabine +paclitaxel(GT chemotherapy), but observation group had oral Huangqi Jiedu decoction additionally. All received chemotherapy for 6 months.Compared clinical effects, total scores of symptoms, levels of serum tumor markers such as carcinoembryonic antigen(CEA) and carbohydrate antigen 15-3(CA15-3), and levels of helper T cells Th1/Th2 cytokines like interleukin-6(IL-2), interferon-γ(IFN-γ), IL-6 before and after treatments, as well as toxic side effects between the two groups. Results The objective response rate(ORR) was 45.1%(23/51)in the observation group, higher than that of control group [29.4%(15/51) ], but the difference was not statistically significant(P>0.05).However, the clinical benefit rate(CBR) of the observation group was significantly higher than that of the control group [78.4%(40/51)vs.58.8%(30/51), P<0.05]. Compared with before treatment, the total scores of symptoms and levels of serum CEA and CA15-3 decreased significantly in both groups after treatment(P<0.05), and even decreased greater in observation group than in control group(P<0.05). The serum levels of IL-2 and IFN-γ and the ratios of IL-2/IL-6 and IFN-γ/IL-6 were significant higher than those before treatment(P<0.05),while the IL-6 level decreased(P<0.05). Moreover, such improvement were found greater in observation group than in control group(P<0.05). Besides, the incidence of toxic and side effects was significantly lower in observation group than in control group [15.7%(8/51)vs.33.3%(17/51), P<0.05]. Conclusion Huangqi Jiedu decoction combined with GT chemotherapy helps mTNBC patients to alleviate the symptoms relevant with weakened body resistance and poison flourishing. It could control tumor progression, correct pathological shift of Th1/Th2 cytokine balance and reduce the side effects of chemotherapy. Consequently, Huangqi Jiedu decoction shows significant advantages in reducing toxicity and enhancing efficacy of chemotherapy.
引文
[1]Székely B, Silber AL, Pusztai L. New Therapeutic Strategies for Triple-Negative Breast Cancer[J]. Oncology(Williston Park), 2017, 31(2):130-137.
[2]Riva F, Bidard FC, Houy A, et al. Patient-Specific Circulating Tumor DNA Detection during Neoadjuvant Chemotherapy in Triple-Negative Breast Cancer[J]. Clin Chem,2017, 63(3):691-699. doi:10.1373/clinchem.2016.262337.
[3]桂奕文,任建琳,朱为康,等.中药联合化疗治疗三阴性乳腺癌疗效Meta分析[J].辽宁中医杂志, 2018, 45(6):1139-1141. doi:10.13192/j. issn.1000-1719.2018.06.005.
[4]王晓庆.黄芪解毒汤联合GT化疗方案对转移性三阴性乳腺癌患者疗效及生存率的影响[J].现代中西医结合杂志, 2018, 27(23):2583-2585. doi:10.3969/j. issn.1008-8849.2018.23.022.
[5]中国抗癌协会乳腺癌专业委员会.中国抗癌协会乳腺癌诊治指南与规范(2015版)[J].中国癌症杂志, 2015,25(9):692-754. doi:10.3969/j. issn.1007-3969.2015.09.010.
[6]戴慎,薛建国,岳沛平.中医病证诊疗标准与方剂选用[M].北京:人民卫生出版社, 2001:305-308.
[7]Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumours:revised RECIST guideline(version 1.1)[J]. Eur J Cancer, 2009, 45(2):228-247.doi:10.1016/j. ejca.2008.10.026.
[8]郑筱萸.中药新药临床研究指导原则(试行)[M].北京:中国医药科技出版社, 2002:378-380.
[9]Qiu J, Xue X, Hu C, et al. Comparison of Clinicopathological Features and Prognosis in Triple-Negative and Non-Triple Negative Breast Cancer[J]. J Cancer, 2016, 7(2):167-173.doi:10.7150/jca.10944.
[10]Gluz O, Nitz U, Liedtke C, et al. Comparison of NeoadjuvantNab-Paclitaxel+CarboplatinvsNabPaclitaxel+Gemcitabine in Triple-Negative Breast Cancer:Randomized WSG-ADAPT-TN Trial Results[J]. J Natl Cancer Inst, 2018, 110(6):628-637. doi:10.1093/jnci/djx258.
[11]刘静,陆德铭.中医药治疗三阴性乳腺癌的临床研究进展[J].山东中医杂志, 2016, 35(11):1015-1017.
[12]Yang Y, Zhang H, Zhang M, et al. Elevation of serum CEA and CA15-3 levels during antitumor therapy predicts poor therapeutic response in advanced breast cancer patients[J]. Oncol Lett, 2017, 14(6):7549-7556. doi:10.3892/ol.2017.7164.
[13]丁玲,刘丽芳,吴世婷,等.黄芪解毒汤含药血清对乳腺癌细胞MCF-7中SHH、PTCH1、SMO、GLI1基因及Cyclin D1蛋白表达的影响[J].中医药导报, 2016, 22(24):23-28.
[14]周丽菁,汪志学,龙婷婷,等.黄芪多糖在体外巨噬细胞-乳腺癌细胞共培养体系中的作用[J].免疫学杂志, 2017, 33(6):469-476. doi:10.13431/j. cnki. immunol.j.20170084.
[15]孔嘉欣,苏旭春,戴诗蕾,等.黄芪多糖防治蒽环类药物心脏毒性的临床观察[J].中国医药导报, 2017, 14(20):136-139.
[16]刘冠璋,董婉茹,于卉,等.玄参水提物对CCL4所致大鼠急性肝损伤的保护作用研究[J].吉林中医药, 2015,35(5):504-507. doi:10.13463/j. cnki. jlzyy.2015.05.022.
[17]Nú?ez C, Lozada-Requena I, Ysmodes T, et al. Immunomodulation of Uncaria tomentosa over dendritic cells, il-12and profile TH1/TH2/TH17 in breast cancer[J]. Rev Peru Med Exp Salud Publica, 2015, 32(4):643-651.
[2]Riva F, Bidard FC, Houy A, et al. Patient-Specific Circulating Tumor DNA Detection during Neoadjuvant Chemotherapy in Triple-Negative Breast Cancer[J]. Clin Chem,2017, 63(3):691-699. doi:10.1373/clinchem.2016.262337.
[3]桂奕文,任建琳,朱为康,等.中药联合化疗治疗三阴性乳腺癌疗效Meta分析[J].辽宁中医杂志, 2018, 45(6):1139-1141. doi:10.13192/j. issn.1000-1719.2018.06.005.
[4]王晓庆.黄芪解毒汤联合GT化疗方案对转移性三阴性乳腺癌患者疗效及生存率的影响[J].现代中西医结合杂志, 2018, 27(23):2583-2585. doi:10.3969/j. issn.1008-8849.2018.23.022.
[5]中国抗癌协会乳腺癌专业委员会.中国抗癌协会乳腺癌诊治指南与规范(2015版)[J].中国癌症杂志, 2015,25(9):692-754. doi:10.3969/j. issn.1007-3969.2015.09.010.
[6]戴慎,薛建国,岳沛平.中医病证诊疗标准与方剂选用[M].北京:人民卫生出版社, 2001:305-308.
[7]Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumours:revised RECIST guideline(version 1.1)[J]. Eur J Cancer, 2009, 45(2):228-247.doi:10.1016/j. ejca.2008.10.026.
[8]郑筱萸.中药新药临床研究指导原则(试行)[M].北京:中国医药科技出版社, 2002:378-380.
[9]Qiu J, Xue X, Hu C, et al. Comparison of Clinicopathological Features and Prognosis in Triple-Negative and Non-Triple Negative Breast Cancer[J]. J Cancer, 2016, 7(2):167-173.doi:10.7150/jca.10944.
[10]Gluz O, Nitz U, Liedtke C, et al. Comparison of NeoadjuvantNab-Paclitaxel+CarboplatinvsNabPaclitaxel+Gemcitabine in Triple-Negative Breast Cancer:Randomized WSG-ADAPT-TN Trial Results[J]. J Natl Cancer Inst, 2018, 110(6):628-637. doi:10.1093/jnci/djx258.
[11]刘静,陆德铭.中医药治疗三阴性乳腺癌的临床研究进展[J].山东中医杂志, 2016, 35(11):1015-1017.
[12]Yang Y, Zhang H, Zhang M, et al. Elevation of serum CEA and CA15-3 levels during antitumor therapy predicts poor therapeutic response in advanced breast cancer patients[J]. Oncol Lett, 2017, 14(6):7549-7556. doi:10.3892/ol.2017.7164.
[13]丁玲,刘丽芳,吴世婷,等.黄芪解毒汤含药血清对乳腺癌细胞MCF-7中SHH、PTCH1、SMO、GLI1基因及Cyclin D1蛋白表达的影响[J].中医药导报, 2016, 22(24):23-28.
[14]周丽菁,汪志学,龙婷婷,等.黄芪多糖在体外巨噬细胞-乳腺癌细胞共培养体系中的作用[J].免疫学杂志, 2017, 33(6):469-476. doi:10.13431/j. cnki. immunol.j.20170084.
[15]孔嘉欣,苏旭春,戴诗蕾,等.黄芪多糖防治蒽环类药物心脏毒性的临床观察[J].中国医药导报, 2017, 14(20):136-139.
[16]刘冠璋,董婉茹,于卉,等.玄参水提物对CCL4所致大鼠急性肝损伤的保护作用研究[J].吉林中医药, 2015,35(5):504-507. doi:10.13463/j. cnki. jlzyy.2015.05.022.
[17]Nú?ez C, Lozada-Requena I, Ysmodes T, et al. Immunomodulation of Uncaria tomentosa over dendritic cells, il-12and profile TH1/TH2/TH17 in breast cancer[J]. Rev Peru Med Exp Salud Publica, 2015, 32(4):643-651.