盐酸安罗替尼联合信迪利单抗治疗标准治疗失败后微卫星稳定型结直肠癌疗效观察

Clinical efficacy of Anlotinib hydrochloride combined with Sintilimab in the treatment of microsatellite stable colorectal cancer after the failure of standard treatment

目的探讨盐酸安罗替尼联合信迪利单抗治疗标准治疗失败后微卫星稳定(MSS)型结直肠癌患者的临床疗效及安全性。方法选择2019年5月至2020年2月新乡医学院第一附属医院收治的36例MSS型结直肠癌患者为研究对象,根据治疗方式将患者分为对照组(n=17)和观察组(n=19)。对照组患者给予盐酸安罗替尼胶囊口服治疗,每日1次,每次10 mg,连续给药2周后停用1周,第2次调整剂量为12 mg,连续给药2周后停用1周,共治疗6个月。观察组患者在对照组治疗基础上给予信迪利单抗注射液静脉输注治疗,每次200 mg,每3周给药1次,共治疗6个月。治疗6个月后,使用实体瘤疗效评定标准1.1版评价临床疗效,包括完全缓解(CR)、部分缓解(PR)、疾病稳定(SD)、疾病进展(PD),计算客观缓解率(ORR)和疾病控制率(DCR)。应用肿瘤病人生活质量评分评估患者生活质量,使用常见不良反应事件评价标准4.0评价药物不良反应。比较2组患者的临床疗效、生活质量及不良反应。结果对照组患者的ORR为5.88%,DCR为35.29%;观察组患者的ORR为15.79%,DCR为52.63%。2组患者的ORR及DCR比较差异无统计学意义(P>0.05)。治疗前,2组患者5个功能子量表及总体生命质量评分比较差异均无统计学意义(P>0.05)。2组患者治疗6个月后躯体功能、情绪功能、总体生命质量评分显著高于治疗前(P<0.05);治疗6个月后,观察组患者躯体功能、情绪功能、总体生命质量评分显著高于对照组(P<0.05),观察组患者角色功能、认知功能、社会功能评分与对照组比较差异无统计学意义(P>0.05)。2组患者治疗前症状子量表评分比较差异无统计学意义(P>0.05);治疗6个后,2组患者疲乏评分高于治疗前,疼痛评分显著低于治疗前(P<0.05);2组患者恶心呕吐评分与治疗前比较差异无统计学意义(P>0.05)。治疗6个月后,观察组患者疼痛评分低于对照组(P<0.05),2组患者疲乏评分及恶心呕吐评分比较差异均无统计学意义(P>0.05)。2组患者治疗6个月后呼吸困难评分、失眠评分及食欲丧失评分显著低于治疗前(P<0.05),2组患者便秘、腹泻、经济影响评分与治疗前比较差异均无统计学意义(P>0.05)。治疗6个月后,观察组患者呼吸困难评分、失眠评分显著低于对照组,食欲丧失评分显著高于对照组(P<0.05);观察组与对照组患者治疗后便秘评分、腹泻评分、经济影响评分比较差异无统计学意义(P>0.05)。对照组患者不良反应发生率为64.17%(11/17),观察组患者不良反应发生率为68.42%(13/19);对照组与观察组患者不良反应发生率比较差异无统计学意义(χ^(2)=0.056,P>0.05)。结论盐酸安罗替尼联合信迪利单抗治疗标准治疗失败后MSS型结直肠癌患者的临床疗效较好,可有效缓解临床症状,改善患者生命质量,且不良反应可控。

Objective To investigate the clinical efficacy and safety of Anlotinib hydrochloride combined with Sintilimab in the treatment of microsatellite stable(MSS)colorectal cancer after the failure of standard treatment.Methods A total of 36 patients with MSS colorectal cancer admitted to the First Affiliated Hospital of Xinxiang Medical University from May 2019 to February 2020 were selected as the research subjects,and they were divided into control group(n=17)and observation group(n=19)according to different treatment methods.The patients in the control group were given Anlotinib hydrochloride capsules orally,once a day,10 mg each time,continuously administrated for two weeks and then stopped for one week,the second dose was adjusted to 12 mg,the treatment lasted for six months.The patients in the observation group were given sintilimab injection intravenously on the basis of the treatment of patients in the control group,200 mg each time,once every three weeks,continuously administrated for two weeks and then stopped for one week,the treatment lasted for six months.After six months of treatment,version 1.1 of the evaluation criteria for the efficacy of solid tumors was used to evaluate the clinical efficacy,including complete remission(CR),partial remission(PR),stable disease(SD),and disease progression(PD).The objective response rate(ORR)and disease control rate(DCR)were calculated.The quality of life score of cancer patients was used to assess the patient′s quality of life,and the 4.0 standard for evaluation of common adverse events was used to evaluate adverse drug reactions.The clinical efficacy,quality of life and adverse reactions of patients between the two groups were compared.Results The ORR,DCR of patients in the control group was 5.88%,35.29%,respectively.The ORR,DCR of patients in the observation group was 15.79%,52.63%,respectively.There was no significant difference in ORR and DCR of patients between the two groups(P>0.05).Before treatment,there was no statistically significant difference in the five functional subscales and overall quality of life scores of the patients between the two groups(P>0.05).The scores of physical function,emotional function and overall quality of life of the patients in the two groups after six months of treatment were significantly higher than those before treatment(P<0.05);after six months of treatment,the scores of physical function,emotional function and overall quality of life of the patients in the observation group were significantly higher than those in the control group(P<0.05).There was no significant differences in the role function,cognitive function and social function scores of the patients between the two groups after six months of treatment(P>0.05).There was no significant difference in the scores of the symptom subscale between the two groups before treatment(P>0.05).After six months of treatment,the fatigue score of the patients in the two groups was significantly higher than that before treatment,and the pain score of the patients was significantly lower than that before treatment(P<0.05).There was no significant difference in the nausea score and vomiting score of patients after six months of treatment compared with those before treatment in the two groups(P>0.05).After six months of treatment,the pain score of the patients in the observation group was significantly lower than that in the control group(P<0.05);and there was no significant difference in fatigue score and nausea and vomiting score of the patients between the two groups(P>0.05).The dyspnea score,insomnia score of the patients after six months of treatment were significantly lower than those before treatment,and the loss of appetite score was significantly higher than that before treatment in the two groups(P<0.05);after six months of treatment,the dyspnea score,insomnia score and loss of appetite score of patients in the observation group were significantly lower than those in the control group(P<0.05);there was no significant difference in constipation score,diarrhea score and economic impact score of patients between the two groups(P>0.05).The incidence of adverse drug reactions in the control group was 64.17%(11/17),and the incidence of adverse drug reactions in the observation group was 68.42%(13/19);there was no significant difference in the incidence of adverse drug reactions between the control group and observation group(χ^(2)=0.056,P>0.05).Conclusion Anlotinib hydrochloride combined with Sintilimab in the treatment of patients with MSS colorectal cancer after the failure of standard treatment has better clinical efficacy,which can effectively relieve clinical symptoms,improve the quality of life of patients,and the adverse drug reactions can be controlled.