经导管肝动脉持续灌注治疗序贯卡培他滨及PD-1抑制剂治疗不可切除肝门部胆管癌的疗效及安全性

Efficacy and safety of hepatic arterial infusion therapy sequential capecitabine and PD⁃1 inhibitor in the treatment of unresectable hilar cholangiocarcinoma

目的探讨经导管肝动脉持续灌注治疗序贯卡培他滨及PD-1抑制剂治疗不可切除肝门部胆管癌的疗效及安全性。方法回顾性分析2019年10月至2021年10月在临沂市肿瘤医院收治的34例不可切除肝门部胆管癌患者的临床资料,所有患者均接受经导管肝动脉持续灌注治疗序贯卡培他滨及PD-1抑制剂治疗,患者先完成2~6个周期mFOLFOX7-肝动脉持续灌注化疗(hepatic arterial infusion chemotherapy,HAIC)以及PD-1抑制剂动脉灌注治疗,灌注治疗后序贯行卡培他滨单药化疗及PD-1抑制剂静脉点滴治疗。观察患者的客观缓解率(objective response rate,ORR)、疾病控制率(disease control rate,DCR)以及不良反应发生情况,分析总生存期(overall survival,OS)及其影响因素。结果34例患者共行介入治疗155次,平均(4.56±1.61)次;接受2个周期介入治疗后ORR为61.76%(21/34),DCR为97.06%(33/34);完成介入治疗后总体ORR为82.35%(28/34),DCR为100.00%(34/34)。中位随访时间为17.5个月,中位OS为20.0个月(95%CI:15.0~25.0个月)。HAIC治疗相关不良反应主要为发热、腹痛、恶心呕吐及化疗药物引起的血液学毒性等,均为1~2级;PD-1抑制剂治疗相关不良反应主要为疲劳、皮疹、体表毛细血管增生等,均≤3级。多因素Cox回归分析显示,导管周浸润型是OS的危险因素(HR=2.051,95%CI:1.039~4.407,P=0.038),介入治疗5~6次为OS的保护因素(HR=0.465,95%CI:0.219~0.853,P=0.006)。结论经导管肝动脉持续灌注治疗序贯卡培他滨及PD-1抑制剂治疗不可切除肝门部胆管癌具有较好的疗效,且不良反应可控,其中生长模式分型和介入治疗次数可影响患者生存率。

Objective To investigate the efficacy and safety of hepatic arterial infusion therapy sequential capecitabine and PD‑1 inhibitor in the treatment of unresectable hilar cholangiocarcinoma.Methods The clinical data of 34 patients of unresectable hilar cholangiocarcinoma admitted to Linyi Cancer Hospital from October 2019 to October 2021 were retrospectively analyzed.All patients received hepatic arterial infusion therapy sequential capecitabine and PD‑1 inhibitor.The patient received 2-6 cycles of mFOLFOX7‑hepatic arterial infusion chemotherapy(HAIC)and PD‑1 inhibitor arterial infusion therapy,and then received capecitabine monotherapy and intravenous drip with PD‑1 inhibitor.The objective response rate(ORR)and disease control rate(DCR)as well as adverse reactions of patients were observed,and the overall survival(OS)and its influencing factors were analyzed.Results A total of 155 interventional treatments were performed in 34 patients,with an average of(4.56±1.61)times.After 2 cycles of intervention treatment,the ORR and the DCR were 61.76%(21/34)and 97.06%(33/34),respectively.After the whole intervention treatment,the overall ORR was 82.35%(28/34),and the DCR was 100.00%(34/34).The median follow‑up time was 17.5 months,and the median OS was 20.0 months(95%CI:15.0-25.0 months).The adverse reactions related to HAIC mainly included fever,abdominal pain,nausea and vomiting,and hematological toxicity caused by chemotherapy drugs,all of which were grade 1-2.The adverse reactions related to PD‑1 inhibitor treatment mainly included fatigue,rash,body surface capillary hyperplasia,all of which were≤grade 3.Multivariable Cox regression analysis showed that periductal infiltrating was a risk factor for OS(HR=2.051,95%CI:1.039-4.407,P=0.038),and 5-6 cycles of intervention treatments was a protective factor for OS(HR=0.465,95%CI:0.219-0.853,P=0.006).Conclusions Hepatic arterial infusion therapy sequential capecitabine and PD‑1 inhibitor are effective in the treatment of unresectable hilar cholangiocarcinoma with controllable adverse reactions,in which the growth pattern classification and the number of intervention treatments may affect the survival rate of patients.