Hepatic arterial infusion of oxaliplatin plus raltitrexed in patients with intermediate and advanced stage hepatocellular carcinoma: A phase II, single-arm, prospective study.

Abstract Purpose To investigate the efficacy and safety of hepatic arterial infusion (HAI) of oxaliplatin plus raltitrexed in patients with intermediate stage and advanced stage hepatocellular carcinoma (HCC). Methods In this phase II, single-arm clinical trial, we enrolled patients aged 18–70 years with intermediate stage and advanced stage HCC, which included patients with HCC at Barcelona Clinic Liver Cancer (BCLC) stage B who experienced transcatheter arterial chemoembolization failure/refractoriness, and those with BCLC stage C with portal vein invasion. We performed HAI with oxaliplatin and raltitrexed. Treatment was repeated every 3 weeks and was discontinued either because of disease progression, unacceptable toxicity levels, or refusal of further treatment. We used Simon's two-stage design. The primary end-point was the objective response rate in accordance with the Response Evaluation Criteria in Solid Tumours. Results Fifty-one patients were screened between January 5, 2018 and August 7, 2019. Of these, 39 patients (34 men and 5 women; median age, 53 years) 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. Treatment-related grade IV adverse events or deaths were not reported, and the observed grade III adverse events were elevated aspartate aminotransferase levels (5 [12.8%]), elevated alanine aminotransferase levels (1 [2.6%]), leukopenia (1 [2.6%]), thrombocytopaenia (1 [2.6%]) and abdominal infection (1 [2.6%]). Conclusion HAI of oxaliplatin plus raltitrexed showed promising efficacy and acceptable toxicity levels in patients with intermediate and advanced stage HCC, and further evaluation is warranted.