Hepatic Arterial Infusion of Oxaliplatin, Fluorouracil, and Leucovorin Versus Transarterial Chemoembolization for Large Hepatocellular Carcinoma: A Randomized Phase III Trial.

Abstract

PURPOSE:

In a previous phase II trial, hepatic arterial infusion chemotherapy (HAIC) with infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX) yielded higher treatment responses than transarterial chemoembolization (TACE) in large unresectable hepatocellular carcinoma. We aimed to compare the overall survival of patients treated with FOLFOX-HAIC versus TACE as first-line treatment in this population.

METHODS:

In this randomized, multicenter, open-label trial, adults with unresectable hepatocellular carcinoma (largest diameter ≥ 7 cm) without macrovascular invasion or extrahepatic spread were randomly assigned 1:1 to FOLFOX-HAIC (oxaliplatin 130 mg/m2, leucovorin 400 mg/m2, fluorouracil bolus 400 mg/m2 on day 1, and fluorouracil infusion 2,400 mg/m2 for 24 hours, once every 3 weeks) or TACE (epirubicin 50 mg, lobaplatin 50 mg, and lipiodol and polyvinyl alcohol particles). The primary end point was overall survival by intention-to-treat analysis. Safety was assessed in patients who received ≥ 1 cycle of study treatment.

RESULTS:

Between October 1, 2016, and November 23, 2018, 315 patients were randomly assigned to FOLFOX-HAIC (n = 159) or TACE (n = 156). The median overall survival in the FOLFOX-HAIC group was 23.1 months (95% CI, 18.5 to 27.7) versus 16.1 months (95% CI, 14.3 to 17.9) in the TACE group (hazard ratio, 0.58; 95% CI, 0.45 to 0.75; P < .001). The FOLFOX-HAIC group showed a higher response rate than the TACE group (73 [46%] v 28 [18%]; P < .001) and a longer median progression-free survival (9.6 [95% CI, 7.4 to 11.9] v 5.4 months [95% CI, 3.8 to 7.0], P < .001). The incidence of serious adverse events was higher in the TACE group than in the FOLFOX-HAIC group (30% v 19%, P = .03). Two deaths in the FOLFOX-HAIC group and two in the TACE group were deemed to be treatment-related.

CONCLUSION:

FOLFOX-HAIC significantly improved overall survival over TACE in patients with unresectable large hepatocellular carcinoma.

• Authors: Qi-Jiong Li, Min-Ke He, Huan-Wei Chen, Wan-Qiang Fang, Yuan-Min Zhou, Li Xu, Wei Wei, Yao-Jun Zhang, Ying Guo, Rong-Ping Guo, Min-Shan Chen, Ming Shi
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 40 Issue 2 Pg. 150-160 (01 10 2022) ISSN: 1527-7755 [Electronic] United States
• PMID: 34648352 (Publication Type: Clinical Trial, Phase III, Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Organoplatinum Compounds
• Oxaliplatin
• Leucovorin
• Fluorouracil

Topics

• Adult
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage, adverse effects)
• Carcinoma, Hepatocellular (drug therapy, mortality, pathology)
• Chemoembolization, Therapeutic (adverse effects, mortality)
• China
• Disease Progression
• Female
• Fluorouracil (administration & dosage, adverse effects)
• Hepatic Artery
• Humans
• Infusions, Intra-Arterial
• Leucovorin (administration & dosage, adverse effects)
• Liver Neoplasms (drug therapy, mortality, pathology)
• Male
• Middle Aged
• Organoplatinum Compounds
• Oxaliplatin (administration & dosage, adverse effects)
• Progression-Free Survival
• Time Factors
• Tumor Burden