A randomized comparative study of high-dose and low-dose hepatic arterial infusion chemotherapy for intractable, advanced hepatocellular carcinoma

Purpose: Hepatic arterial infusion chemotherapy (HAIC) has been reported to be effective in patients with advanced hepatocellular carcinoma (HCC). Methods: In this multicenter, prospective, open-labeled, clinical trial, we randomly assigned 68 patients with advanced HCC to receive either low-dose [n = 32, 5-fluorouracil (FU), 170 mg/m² and cisplatin, 7 mg/m² on days 1-5] or high-dose HAIC (n = 36, 5-FU, 500 mg/m² on days 1-3 and cisplatin, 60 mg/m² on day 2) every 4 weeks via an implantable port system. Results: A total of 207 cycles of HAIC was given to the 68 patients. Overall, 6 patients (8.8%) achieved a partial response and 21 patients (30.9%) had stable disease. The objective response rate (CR + PR) was significantly improved in the high-dose group compared to the low-dose group (16.7% vs. 0%, P = 0.024). The median time to disease progression and overall survival were slightly prolonged in the high-dose group compared to the low-dose group (median survival, 193 vs. 153 days; P = 0.108; median time to disease progression, 145 vs. 90 days; P = 0.095). Multivariate analysis showed that tumor response to treatment [P = 0.007, RR 2.27 (95% CI, 1.248-4.132)] was the only factor associated with overall survival. All adverse events were tolerable and successfully managed in both treatment groups. Conclusions: Both HAIC regimens are safe and effective in patients with advanced HCC. High-dose HAIC achieves a better tumor response compared to low-dose HAIC.