Clinical study of teriprizumab injection combined with XP regimen in the treatment of advanced gastric cancer
-
摘要: 目的 探讨特瑞普利单抗注射液联合XP方案对胃癌晚期的疗效及其对免疫功能的影响。方法 选择2019年6月—2020年12月在我院确诊为晚期胃癌的患者86例，按照随机数字的方法将患者分为观察组和对照组，每组43例。对照组予以XP方案化疗，观察组在对照组的基础上予以特瑞普利单抗治疗。观察并比较2组治疗后疗效及不良反应，以及2组治疗前后癌胚抗原(CEA)、糖抗原(CA)199、CA242、可溶性程序性死亡1(sPD-1)、可溶性T细胞免疫球蛋白黏蛋白分子3(sTim-3)和可溶性淋巴细胞活化基因-3(sLAG-3)、干扰素(INF)-γ、白细胞介素(IL)-10、IL-4和转化生长因子-β(TGF-β)水平的变化。结果 观察组总有效率为97.67%，明显高于对照组的79.07%(P< 0.05);2组不良反应发生率比较，差异无统计学意义。2组治疗前血清CEA、CA199、CA242、sPD-1、sTim-3、sLAG-3、INF-γ、IL-10、IL-4和TGF-β水平比较，差异无统计学意义; 2组治疗后血清INF-γ和IL-10水平较治疗前明显升高(P< 0.01)，而血清CEA、CA199、CA242、sPD-1、sTim-3、sLAG-3、IL-4和TGF-β水平较治疗前明显降低(P< 0.01)，且观察组与对照组比较升高或降低更为明显(P< 0.01)。结论 特瑞普利单抗注射液联合XP方案对胃癌晚期的疗效显著，可降低肿瘤标记物的水平，其机制可能与纠正Th1/Th2紊乱有关。Abstract: Objective To explore the efficacy of teriprizumab injection combined with XP regimen in the treatment of patients with advanced gastric cancer and its impact on immune function.Methods A total of 86 patients diagnosed with advanced gastric cancer in our hospital from June 2019 to December 2020 were enrolled. They were divided into observation group and control group according to the random number method, with 43 cases in each group. Patients in the control group were given XP regimen chemotherapy, and patients in the observation group were given teriprizumab based on the control group. The efficacy and adverse events were observed and compared in two groups. The levels of carcinoembryonic antigen(CEA), carbohydrate antigen(CA) 199, CA242, soluble programmed death 1(sPD-1), soluble T cell immunoglobulin mucin molecule 3(sTim-3) and soluble lymphocyte activation gene-3(sLAG-3), interferon(INF)-γ, interleukin(IL)-10, IL-4 and transforming growth factor-β(TGF-β) were compared between two groups before and after treatment.Results The total effective rate was 97.67% in the observation group, significantly higher than 79.07% in the control group(P< 0.05). There was no significant difference in adverse events between the two groups. There was no significant difference in serum CEA, CA199, CA242, sPD-1, sTim-3, sLAG-3, INF-γ, IL-10, IL-4, and TGF-β levels between the two groups before treatment. After treatment, the serum levels of INF-γ and IL-10 in two groups were significantly higher than those before treatment(P< 0.01), while the serum levels of CEA, CA199, CA242, sPD-1, sTim-3, sLAG-3, IL-4, and TGF-β were significantly lower than those before treatment(P< 0.01), and the increased or decreased levels in the observation group were more obvious compared with the control group(P< 0.01).Conclusion The efficacy of teriprizumab injection combined with XP regimen is obvious in treating patients with advanced gastric cancer. It can significantly reduce the levels of tumor markers. The mechanism may be related to the correction of Th1/Th2 disorders.
-
Key words:
- teriprizumab /
- chemotherapy /
- advanced gastric cancer /
- immune function /
- targeted therapy
-
-
表 1 2组疗效比较
例(%) 组别 例数 完全缓解 部分缓解 稳定 进展 总有效 观察组 43 4(9.30) 30(69.77) 8(18.60) 1(2.33) 42(97.67)1) 对照组 43 2(4.65) 22(51.16) 10(23.26) 9(20.93) 34(79.07) 与对照组比较，1)P < 0.05。 
下载: 导出CSV
表 2 2组治疗前后血清CEA、CA199和CA242水平比较
X±S 组别 例数 CEA/(μg·L-1) CA199/(U·mL-1) CA242/(mg·L-1) 治疗前 治疗后 治疗前 治疗后 治疗前 治疗后 观察组 43 73.28±3.28 15.38±2.731)2) 79.18±4.17 18.27±3.841)2) 91.37±7.27 35.19±6.291)2) 对照组 43 74.17±4.21 28.73±3.171) 79.72±5.03 32.28±4.181) 92.13±8.39 53.27±7.171) 与同组内治疗前比较，1)P < 0.01;与对照组比较，1)P < 0.01。
下载: 导出CSV
表 3 2组治疗前后血清sPD-1、sTim-3和sLAG-3水平比较
ng/mL，X±S 组别 例数 sPD-1 sTim-3 sLAG-3 治疗前 治疗后 治疗前 治疗后 治疗前 治疗后 观察组 43 1.73±0.35 0.67±0.181)2) 2.87±0.53 0.83±0.171)2) 143.97±47.32 59.32±12.731)2) 对照组 43 1.71±0.42 0.93±0.271) 2.83±0.48 1.76±0.351) 148.35±51.83 97.19±19.421) 与同组内治疗前比较，1)P < 0.01;与对照组比较，1)P < 0.01。
下载: 导出CSV
表 4 2组治疗前后血清INF-γ、IL-10、IL-4和TGF-β水平比较
X±S 组别 例数 INF-γ/(ng·mL-1) IL-10/(pg·mL-1) IL-4/(pg·mL-1) TGF-β/(nmol·L-1) 治疗前 治疗后 治疗前 治疗后 治疗前 治疗后 治疗前 治疗后 观察组 43 1.38±
0.273.21± 0.651)2) 15.27±2.64 25.37± 4.821)2) 38.35±5.29 21.32± 3.281)2) 27.62±5.31 11.72± 2.181)2) 对照组 43 1.31±0.21 2.63± 0.571) 15.48±2.73 16.28± 3.171) 39.17±6.17 28.37± 4.191) 27.18±4.29 17.81± 3.631) 与同组内治疗前比较，1)P < 0.01;与对照组比较，1)P < 0.01。
下载: 导出CSV
表 5 2组不良反应发生率比较
例(%) 组别 例数 骨髓抑制 胃肠道反应 肝功能损害 手足综合征 观察组 43 12(27.91) 41(95.35) 13(30.23) 10(23.26) 对照组 43 9(20.93) 38(88.37) 10(23.26) 12(27.91)
下载: 导出CSV
-
[1] Johnston FM, Beckman M. Updates on Management of Gastric Cancer[J]. Curr Oncol Rep, 2019, 21(8): 67. doi: 10.1007/s11912-019-0820-4
[2] Matsuoka T, Yashiro M. Biomarkers of gastric cancer: Current topics and future perspective[J]. World J Gastroenterol, 2018, 24(26): 2818-2832. doi: 10.3748/wjg.v24.i26.2818
[3] Venerito M, Vasapolli R, Rokkas T, et al. Gastric cancer: epidemiology, prevention, and therapy[J]. Helicobacter, 2018, 23(Suppl 1): e12518.
[4] Wu X, Gu Z, Chen Y, et al. Application of PD-1 Blockade in Cancer Immunotherapy[J]. Comput Struct Biotechnol J, 2019, 17: 661-674. doi: 10.1016/j.csbj.2019.03.006
[5] 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
[6] Kennedy LB, Salama A. A review of cancer immunotherapy toxicity[J]. CA Cancer J Clin, 2020, 70(2): 86-104. doi: 10.3322/caac.21596
[7] Smyth EC, Nilsson M, Grabsch HI, et al. Gastric cancer[J]. Lancet, 2020, 396(10251): 635-648. doi: 10.1016/S0140-6736(20)31288-5
[8] 戴亮, 杨永波, 石秋玲, 等. 食管鳞癌新辅助治疗后淋巴结阳性病人行特瑞普利单克隆抗体辅助治疗的多中心、前瞻性、随机对照临床研究设计[J]. 中华消化外科杂志, 2021, 20(6): 655-659. doi: 10.3760/cma.j.cn115610-20210413-00180
[9] Datar I, Sanmamed MF, Wang J, et al. Expression Analysis and Significance of PD-1, LAG-3, and TIM-3 in Human Non-Small Cell Lung Cancer Using Spatially Resolved and Multiparametric Single-Cell Analysis[J]. Clin Cancer Res, 2019, 25(15): 4663-4673. doi: 10.1158/1078-0432.CCR-18-4142
[10] Yu H, Boyle TA, Zhou C, et al. PD-L1 Expression in Lung Cancer[J]. J Thorac Oncol, 2016, 11(7): 964-975. doi: 10.1016/j.jtho.2016.04.014
[11] Acharya N, Sabatos-Peyton C, Anderson AC. Tim-3 finds its place in the cancer immunotherapy landscape[J]. J Immunother Cancer, 2020, 8(1): e000911. doi: 10.1136/jitc-2020-000911
[12] Burugu S, Dancsok AR, Nielsen TO. Emerging targets in cancer immunotherapy[J]. Semin Cancer Biol, 2018, 52(Pt 2): 39-52.
[13] Long L, Zhang X, Chen F, et al. The promising immune checkpoint LAG-3: from tumor microenvironment to cancer immunotherapy[J]. Genes Cancer, 2018, 9(5-6): 176-189. doi: 10.18632/genesandcancer.180
[14] Hou M, Zhou N, Li H, et al. Morphine and ketamine treatment suppress the differentiation of T helper cells of patients with colorectal cancer in vitro[J]. Exp Ther Med, 2019, 17(1): 935-942.
[15] Wu TH, Yeh KY, Wang CH, et al. The Combination of Astragalus membranaceus and Angelica sinensis Inhibits Lung Cancer and Cachexia through Its Immunomodulatory Function[J]. J Oncol, 2019, 2019: 9206951.
[16] Zhang YJ, Min Q, Huang Y, et al. Efficacy of Acupuncture and Moxibustion as a Subsequent Treatment after Second-Line Chemotherapy in Advanced Gastric Cancer[J]. Evid Based Complement Alternat Med, 2020, 2020: 8274021.
[17] Shakibapour M, Shojaie B, Yousofi DH. Immunization with Hydatid Cyst Wall Antigens Can Inhibit Breast Cancer through Changes in Serum Levels of Th1/Th2 Cytokines[J]. Int J Prev Med, 2020, 11: 189.
[18] Ma W, Wang K, Du J, et al. Multi-dose parecoxib provides an immunoprotective effect by balancing T helper 1(Th1), Th2, Th17 and regulatory T cytokines following laparoscopy in patients with cervical cancer[J]. Mol Med Rep, 2015, 11(4): 2999-3008. doi: 10.3892/mmr.2014.3003
-