Tyrosine kinase inhibitors, immune checkpoint inhibitors combined with hepatic arterial infusion of oxaliplatin and raltitrexed versus oxaliplatin, 5-fluorouracil and leucovorin for intermediate and advanced hepatocellular carcinoma: A retrospective study

Abstract

Background: Hepatic arterial infusion chemotherapy (HAIC) has demonstrated promising benefits in treating advanced hepatocellular carcinoma (HCC). In China, the most frequently used HAIC regimen is oxaliplatin, 5-fluorouracil, and leucovorin (FOLFOX). However, arterial infusion of fluorouracil over 46 h was not convenient. Raltitrexed, another antimetabolic agent with a long plasma half-life, allows for shorter infusion durations. We aimed to compare the effectiveness and toxicity of tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) combined with HAIC with raltitrexed plus oxaliplatin (RALOX) or FOLFOX in patients with intermediate and advanced HCC.

Methods: This retrospective study enrolled 82 eligible patients from February 2019 to December 2021. Forty patients were treated with FOLFOX HAIC (oxaliplatin 85 mg/m², leucovorin 400 mg/m², 5-fluorouracil bolus 400 mg/m² administered on day 1, and 5-fluorouracil 2400 mg/m² infusion for 46 h, every 3 weeks) combined with TKIs and ICIs. Forty-two patients received RALOX HAIC (oxaliplatin 100 mg/m² and raltitrexed 3 mg/m² on day 1, every 3 weeks) combined with TKIs and ICIs. We compared the objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety profile.

Results: ORR was similar between the FOLFOX HAIC and RALOX HAIC groups (42.5% vs 42.5%, P = 0.974). DCR also showed no significant difference between the two groups (87.5% vs 85.7%, P = 0.813). Median PFS was 10.7 months in the FOLFOX HAIC group versus 10.2 months in the RALOX HAIC group (P = 0.41). Median OS was 20.3 months in the FOLFOX HAIC group, compared to 17.7 months in the RALOX HAIC group (P = 0.50). Both groups had similar profiles of grade 3/4 treatment-related adverse events, including thrombocytopenia, increased aspartate aminotransferase, increased alanine aminotransferase, and leukocytopenia.

Conclusion: The effectiveness and safety of HAIC with RALOX were comparable to HAIC with FOLFOX in intermediate and advanced HCC patients.

Keywords: FOLFOX; Hepatic arterial infusion chemotherapy; Hepatocellular carcinoma; ICI; RALOX; TKI.