To evaluate the efficacy and safety of cinobufotalin in the treatment of postoperative pain in patients with primary liver cancer (PLC) undergoing hepatic arterial infusion chemotherapy (HAIC).

Clinical data of 161 PLC patients treated with HAIC in Sun Yat-sen University Cancer Center from September 2021 to January 2024 were retrospectively analyzed. The informed consents of all patients were obtained and the local ethical committee approval was received. Among them, 152 patients were male and 9 female, aged from 27 to 74 years, with a median age of 54 years. All patients were divided into the cinobufotalin group (n=71) and control group (n=90) according to whether they received cinobufotalin treatment. The degree of pain was assessed by visual analogue scale (VAS). The incidence of moderate and severe pain and use of analgesic drugs between two groups were compared by Chi-square test. The effect of different factors on cinobufotalin in the treatment of moderate and severe pain was analyzed by forest plot. The changes of platelet (Plt) count and liver function indexes between two groups were compared by t-test or Mann-Whitney U test.

At 24-48 h after HAIC, the incidence of moderate and severe pain in the cinobufotalin group was 6% (4/71), significantly lower than 18% (16/90) in the control group (χ²=4.30, P=0.04). Within 24 h after HAIC, the incidence of moderate and severe pain in the cinobufotalin and control groups was 37% (26/71) and 36% (32/90), respectively, and the difference was not statistically significant (χ²=0.00, P>0.05). Forest plot subgroup analysis showed that the incidence of severe pain at 24-48 h after HAIC among male patients, aged 50 years, positive HBsAg, ALT>50 U/L, AST>40 U/L, TB>17.1 μmol/L, no use of iodized oil, lesion size>10 cm, no portal vein tumor thrombus and albumin-bilirubin (ALBI) in the cinobufotalin group was significantly lower than that in the control group (OR=0.88, 0.87, 0.88, 0.80, 0.84, 0.80, 0.80, 0.85, 0.90, 0.83; all P<0.05). After HAIC, no significant difference was observed in the use of analgesic drugs, the changes of Plt and liver function indexes and the incidence of adverse reactions between two groups (all P>0.05).

HAIC combined with cinobufotalin can reduce the incidence of moderate and severe pain, improve the quality of life and enhance the compliance with treatment in patients with PLC.