PD1抑制剂联合呋喹替尼及TAS-102后线治疗晚期结直肠癌的临床价值研究

The clinical value of PD1 inhibitor combined with furoquantinib and TAS⁃102 posterior therapy for advanced colorectal cancer

目的 探讨PD1抑制剂联合呋喹替尼及TAS-102后线治疗晚期肠癌的临床价值和安全性。方法 本研究为回顾性分析,收集标准治疗失败的晚期肠癌病例共30例,其中12例设为观察组,18例设为对照组。观察组采用PD1抑制剂联合呋喹替尼及TAS-102治疗,对照组予PD1抑制剂联合呋喹替尼。PD1抑制剂为信迪利单抗200 mg、替雷利珠200 mg或赛帕利单抗240 mg,呋喹替尼3~5 mg口服两周停一周,TAS-102 25 mg/m~2,第1-5、8-12天每日早、晚餐后口服,21 d 1个周期。整理数据分析两组的客观有效率(ORR)、疾病控制率(DCR)、不良反应,并定期随访观察其无进展生存期(PFS)。结果 截至随访结束时间(2023年3月20日),对照组ORR为11.11%,DCR为33.33%,中位PFS为6.2个月,观察组ORR为25.00%,DCR为83.33%,中位PFS为8.6个月。两组ORR差异无显著性,而DCR和PFS差异有统计学意义。两组不良反应主要为皮疹、肝功能异常、消化道溃疡、甲状腺功能减退、口腔溃疡,两组患者的不良反应均较轻。与对照组相比,观察组3例患者出现腹痛,减药后缓解,7例出现1-2级骨髓抑制,经粒细胞集落刺激因子治疗后恢复。结论 与PD1抑制剂联合呋喹替尼相比,在此基础上再联合TAS-102,晚期结直肠癌患者的生存期可能延长,不良反应均能耐受,该方案可能会成为后线治疗晚期结直肠癌的新策略。

Objective To explore the clinical value and safety of PDI inhibitor combined with furoquan-tinib and TAS-102 in the treatment of advanced colorectal cancer.Methods This study is a retrospective analysis,collected a total of 30 late stage colorectal cancer cases that failed standard treatment.Among the 30 case,12 cases were set as the observation group,and 18 cases were set as the control group.The observation group was treated with PD1 inhibitor combined with furoquantinib and TAS-102,while the control group was treated with PD1 inhibitor combined with furoquantinib.PD1 inhibitors include Xindilizumab 200 mg,Tirelizumab 200 mg,or Sepalizumab 240 ng.3~5 mg Furoquantinib is received orally for two weeks and stopped for one week.TAS-102(25 mg/m2)was taken orally after breakfast and dinner on days 1 to 5 and 8 to 12,with a cycle of 21 days.Data were organized data to analyze the objective response rate(ORR),disease control rate(DCR),adverse reactions of the two groups,and patients were regularly followed up to observe their progression free survival(PFS).Results Until the end of follow-up(March 20,2023),the ORR and DCR of the control group were 11.11%,33.33%,and the median PFS was 6.2 months.The objective response rate of the observation group was 25.00%,white DCR was 83.33%,and median PF was 8.6 months.There was no significant difference in 0RR between the two groups,while the differences in DCR and PFS were statistically significant.The main adverse reactions in both groups were rash,liver dysfunction,gastrointestinal ulcers,hypothyroidism,and oral ulcers.The adverse reactions in both groups were mild.Compared with the control group,3 patients in the observation group had abdominal pain,which was relieved after drug reduction,and 8 patients had 1-2 levels of bone marrow depression,which recovered after colony-stimulating factor treatment.Conclusions Compared with PD1 inhibitor combined with furoquantinib,the combination of TAS102 on this basis can prolong the survival period of patients with advanced colorectal cancer and tolerate adverse reactions.This regimen has the potential to become a new strategy for the third line treatment of advanced colorec-tal cancer.