A phase I study of continuous hepatic arterial infusion of Irinotecan in patients with locally advanced hepatocellular carcinoma

Abstract Purpose Aim of this phase I study was to identify the maximum tolerated dose and dose limiting toxicity of continuous infusion of Irinotecan through a port-a-cath placed in the hepatic artery in patients with hepatocellular carcinoma and cirrhosis to explore new strategies in advanced hepatocellular carcinoma. Response rate and time-to-progression were analysed. Methods Irinotecan was delivered as a five-day continuous infusion every 21 days, with increases of 2.5 mg/m 2 /day every three patients, starting from 7.5 mg/m 2 /day. Dose limiting toxicity corresponded to one patient in each triplet developing G4 haematological or G3 non-haematological toxicity, confirmed in two triplets. Twenty-eight patients (17 Child-Pugh A, 11 B) received treatment and tumour response was assessed after three courses completed by 22 patients. Results Dose limiting toxicity was G3 diarrhoea in two patients, reached at 27.5 mg/m 2 /day and the recommended dose was set at 25 mg/m 2 /day. Nineteen of 30 patients experienced adverse events related to porth-a-cath placement and one died from liver ischemia and sepsis. Median time-to-progression was 11.3 months. Conclusion Intrarterial infusion of Irinotecan is feasible in patients with hepatocellular carcinoma on cirrhosis at a recommended dose of 25 mg/m 2 /day, with no major adverse drug-related events, but with some concerns about the insertion and management of the intra-arterial device.