Hepatic Arterial Infusion of Oxaliplatin Plus Raltitrexed in Patients with Intermediate- and Advanced-Stage Hepatocellular Carcinoma (HAIROX): A Phase II, Single-Arm, Prospective Study

Abstract

Background: Hepatic arterial infusion of oxaliplatin plus fluorouracil could improve the outcomes of patients with advanced hepatocellular carcinoma. Fluorouracil is inconvenient for arterial infusion because it requires prolonged infusion. Conversely, raltitrexed, another antimetabolic drug, could be used in short infusions. We aimed to investigate the efficacy and safety of hepatic arterial infusion of oxaliplatin plus raltitrexed in patients with intermediate- and advanced-stage hepatocellular carcinoma. Patients and methods: We enrolled patients aged 18-70 years with intermediate-stage hepatocellular carcinoma with chemoembolisation failure/refractoriness and advanced-stage hepatocellular carcinoma with portal vein invasion. We performed hepatic arterial infusion with oxaliplatin (100 mg/m2 infusion for 4 hours) and raltitrexed (3 mg/m2 for 1 hour). Treatment was repeated every 3 weeks and was discontinued either because disease progression did not allow further treatment, toxicity levels were unacceptable, or the patient refused further treatment. The primary endpoint was the objective response rate according to the Response Evaluation Criteria in Solid Tumors version 1.1. Results: Fifty-one patients were screened between 5 January, 2018 and 7 August, 2019. Of these, 39 patients were enrolled and included in the intention-to-treat population. Objective response was achieved in 18 (51.4%) of 35 patients in the per-protocol population and in 18 (46.2%) of 39 patients in the intention-to-treat population. There were no reports of treatment-related grade 4 adverse events or deaths, and the observed grade 3 adverse events were elevated aspartate aminotransferase levels (5[12.8%]), elevated alanine aminotransferase levels (1 [2.6%]), leukopenia (1 [2.6%]), thrombocytopenia (1 [2.6%]), and abdominal infection (1 [2.6%]). Conclusion: Hepatic arterial infusion of oxaliplatin plus raltitrexed showed promising efficacy and acceptable toxicity levels in patients with intermediate- and advanced-stage hepatocellular carcinoma, and a multi-centre, phase III trial is expected. Clinical Trial Registration: This study is registered with www.chictr.org.cn, number ChiCTR-OOC-17014182. Funding Statement: This work was supported by the Guiding Project of Science and Technology Planning Project in Fujian Province, China (grant number 2019Y0060). Declaration of Interests: The authors have declared no conflicts of interest. Ethical Approval Statement: The trial was approved by the Ethics Committee of Fujian Cancer Hospital and was performed according to the Declaration of Helsinki. All patients involved in the trial provided written informed consent.