广西医学

目的探讨TAS⁃102联合瑞戈非尼和信迪利单抗在标准方案治疗失败的转移性结直肠癌（mCRC）患者中的应用效果与安全性。方法采用随机数字表法将108例mCRC患者分为观察组和对照组，每组54例。对照组患者接受信迪利单抗联合瑞戈非尼治疗。在对照组治疗方案的基础上，观察组患者同时接受TAS⁃102治疗。比较两组治疗2个周期后的临床疗效，治疗前后血清肿瘤标志物［癌胚抗原（CEA）、糖类抗原（CA）242、CA19⁃9水平］、免疫功能指标［CD3+ T淋巴细胞水平、CD4+ T淋巴细胞水平及CD4+ T淋巴细胞/CD8+ T淋巴细胞比值（CD4+/CD8+）］，以及不良反应发生情况。结果观察组的疾病控制率高于对照组（P<0.05）。治疗后，两组的CEA、CA242、CA19⁃9水平较治疗前降低（P<0.05），CD3+ T淋巴细胞水平、CD4+ T淋巴细胞水平及CD4+/CD8+ 较治疗前升高（P<0.05），且观察组的CEA、CA242、CA19⁃9水平低于对照组，CD3⁺ T淋巴细胞水平、CD4⁺ T淋巴细胞水平及CD4⁺/CD8⁺高于对照组（P<0.05）。治疗期间，两组均未出现3级及以上不良反应，观察组的不良反应总发生率低于对照组（P<0.05）。结论相较于瑞戈非尼联合信迪利单抗，TAS⁃102联合瑞戈非尼和信迪利单抗可提升标准方案治疗失败的mCRC患者的临床疗效，有效降低血清肿瘤标志物水平，改善机体免疫功能，且安全性较好。

Objective To explore the application effect and safety of TAS⁃102 combined with regorafenib and sintilimab in patients with metastatic colorectal cancer (mCRC) who had failed treatment with standard regimen. Methods A total of 108 mCRC patients were assigned to observation group or control group using the random number table method, with 54 cases in each group. The control group received sintilimab combined with regorafenib for treatment, based on which the observation group received simultaneously TAS⁃102 for treatment. Clinical efficacy after 2 treatment cycles, pre⁃ and post⁃treatment serum levels of tumor markers (carcinoembryonic antigen ［CEA］, carbohydrate antigen ［CA］242, CA19⁃9), and immune function indices (CD3+ T lymphocytes level, CD4+ T lymphocytes level, and CD4+ T lymphocytes⁃to CD8+ T lymphocytes ratio ［CD4+/CD8+］), as well as the occurrence of adverse reactions were compared between patients of the two groups. Results The observation group exhibited a higher disease control rate as compared with the control group (P<0.05). After treatment, patients of both groups obtained decreased levels of CEA, CA242, and CA19⁃9 (P<0.05), whereas elevated levels of CD3+ T lymphocytes, CD4+ T lymphocytes, and a increased CD4+/CD8+ as compared with before treatment (P<0.05); in addition, the observation group yielded lower levels of CEA, CA242, and CA19⁃9, whereas higher levels of CD3+ T lymphocytes, CD4+ T lymphocytes, as well as a higher CD4+/CD8+ as compared with the control group (P<0.05). During treatment, no grade 3 or above adverse reactions occurred in the two groups, and the total incidence rate of adverse reactions in the observation group was lower than that in the control group (P<0.05). Conclusion Compared with regorafenib combined with sintilimab, TAS⁃102 combined with regorafenib and sintilimab improves clinical efficacy in mCRC patients who had failed treatment with standard regimen, effectively decreases levels of serum tumor markers, ameliorates immune function of the body, exerting a favorable safety.