Abstract

PurposeOur previous study showed that hepatic arterial infusion chemotherapy (HAIC) using oxaliplatin, fluorouracil, and leucovorin (FOLFOX) plus sorafenib provided a significant survival benefit over sorafenib for advanced hepatocellular carcinoma. However, it is unclear whether the survival benefit should be attributed to the synergism between HAIC and sorafenib or just HAIC alone. We aim to compare HAIC using FOLFOX plus sorafenib with HAIC alone in patients with advanced hepatocellular carcinoma.Materials and MethodsThis was a retrospective study including 225 eligible patients treated with HAIC using FOLFOX (HAIC alone group, n=126, oxaliplatin 85 mg/m², leucovorin 400 mg/m², fluorouracil bolus 400 mg/m² and 2400 mg/m² for 46 hours, every 3 weeks) alone or HAIC plus sorafenib (soraHAIC group, n=99, sorafenib 400 mg twice daily). Survival curves were calculated by the Kaplan-Meier method, and propensity-score matching was used to reduce bias.ResultsThe soraHAIC group showed a longer overall survival (12.9 [95% CI, 10.4-15.4] vs. 10.5 [95% CI, 9.5-11.5] months, HR=0.71 [95% CI, 0.53-0.96]; P=0.025), a better progression free survival (7.0 [95% CI, 5.3-8.8] vs. 5.3 [95% CI, 3.5-7.1] months, HR=0.76 [95% CI, 0.58-0.99]; P=0.046), and a higher disease control rate (RECIST 1.1: 74.8% vs. 61.1%, P=0.030) than the HAIC alone group. In multivariate analysis, soraHAIC was an independent favor factor for survival. In terms of the grade 3/4 adverse event, hand–foot skin reaction was more frequent in the soraHAIC group than the HAIC alone group. In the propensity-score matched cohorts (93 pairs), the overall survival, the progression free survival and disease control rates in the soraHAIC group were also better than those in the HAIC group (P<0.05).ConclusionHAIC plus sorafenib may improve overall survival and progression free survival compared with HAIC alone as initial treatment for advanced hepatocellular carcinoma.

Highlights

  • Hepatocellular carcinoma (HCC) is one of the most common human malignancies in the world, ranking as the second leading cause of cancer-related death [1]

  • hepatic arterial infusion chemotherapy (HAIC) plus sorafenib may improve overall survival and progression free survival compared with HAIC alone as initial treatment for advanced hepatocellular carcinoma

  • In 2018, a large sample retrospective study showed that hepatic arterial infusion of oxaliplatin, fluorouracil, and leucovorin (FOLFOX) monotherapy can significantly improve survival compared with sorafenib for advanced HCC [10]

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Summary

Introduction

Hepatocellular carcinoma (HCC) is one of the most common human malignancies in the world, ranking as the second leading cause of cancer-related death [1]. The traditional standard treatment for these patients is sorafenib, which has suffered from high-level heterogeneity of individual response [4] and median overall survival time (OS) of only 6.5-10.7 months [5, 6]. As an alternative therapy to sorafenib, hepatic arterial infusion chemotherapy (HAIC) is recommended for advanced HCC in Japan [7], with high response rates, favorable long-term outcomes, and acceptable toxicities [8, 9]. In 2018, a large sample retrospective study showed that hepatic arterial infusion of oxaliplatin, fluorouracil, and leucovorin (FOLFOX) monotherapy can significantly improve survival compared with sorafenib for advanced HCC (median OS 14.5 vs 7.0 months; P

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