Abstract: 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.

Key words: Hilar cholangiocarcinoma, Hepatic arterial infusion chemotherapy, PD-1 inhibitor, Capecitabine