Modified hepatic arterial infusion chemotherapy protocol for reducing perioperative pain and anesthetic consumption in patients with hepatocellular carcinoma.

Background: Hepatic arterial infusion chemotherapy (HAIC) with the FOLFOX (folinic acid + fluorouracil + oxaliplatin) regimen has emerged as a crucial treatment for advanced hepatocellular carcinoma (HCC), but oxaliplatin-induced neuropathic pain significantly reduces patients' quality of life. This study investigated the impact of modified HAIC procedures on perioperative pain levels and analgesic requirements in patients with HCC. Methods: This single-institution retrospective study analyzed 180 patients with HCC undergoing HAIC. Patients were divided into three groups: Group A (n=40), which received the standard FOLFOX-HAIC regimen; Group B (n=74), which received a reverse sequence FOLFOX-HAIC (REFOLFOX-HAIC), with oxaliplatin administered after fluorouracil and leucovorin; and Group C (n=67), which received a direct intraoperative infusion of oxaliplatin with FOLFOX-HAIC (OxDirect-FOLFOX-HAIC). The primary endpoints were the intraoperative and 24-hour postoperative analgesic utilization score and visual analogue scale (VAS) pain scores. Secondary outcomes included tumor response and safety. Results: Both modified protocols demonstrated superior pain management. Compared to the standard regimen (Group A), both Group B (REFOLFOX-HAIC) and Group C (OxDirect-FOLFOX-HAIC) showed significantly lower analgesic utilization scores (P=0.021 and P=0.027, respectively). Similarly, VAS pain scores were significantly reduced in Group B and Group C (P=0.019 and P=0.039, respectively). Importantly, these modifications did not compromise therapeutic efficacy; after 3 months, there were no statistically significant differences between Groups A-C in terms of objective response rates (15.00% vs. 13.70% vs. 8.96%; P=0.074) or disease control rates (95.00% vs. 89.04% vs. 98.51%; P=0.591). The safety profiles were comparable, with no grade-3-or-higher adverse events reported. Conclusions: The REFOLFOX-HAIC and OxDirect-FOLFOX-HAIC procedures significantly reduced perioperative pain and the need for analgesics in patients with HCC as compared to the conventional FOLFOX-HAIC protocol, without compromising short-term tumor control or safety.