Idarubicin-loaded beads for chemoembolisation of hepatocellular carcinoma: results of the IDASPHERE phase I trial

BackgroundA phase I dose-escalation trial of transarterial chemoembolisation (TACE) with idarubicin-loaded beads was performed in cirrhotic patients with hepatocellular carcinoma (HCC). AimTo estimate the maximum-tolerated dose (MTD) and to assess safety, efficacy, pharmacokinetics and quality of life. MethodsPatients received a single TACE session with injection of 2mL drug-eluting beads (DEBs; DC Bead 300-500m) loaded with idarubicin. The idarubicin dose was escalated according to a modified continuous reassessment method. MTD was defined as the dose level closest to that causing dose-limiting toxicity (DLT) in 20% of patients. ResultsTwenty-one patients were enrolled, including nine patients at 5mg, six patients at 10mg, and six patients at 15mg. One patient at each dose level experienced DLT (acute myocardial infarction, hyperbilirubinaemia and elevated aspartate aminotransferase (AST) at 5-, 10- and 15-mg, respectively). The calculated MTD of idarubicin was 10mg. The most frequent grade 3 adverse events were pain, elevated AST, elevated -glutamyltranspeptidase and thrombocytopenia. At 2months, the objective response rate was 52% (complete response, 28%, and partial response, 24%) by modified Response Evaluation Criteria in Solid Tumours. The median time to progression was 12.1months (95% CI 7.4months - not reached); the median overall survival was 24.5months (95% CI 14.7months - not reached). Pharmacokinetic analysis demonstrated the ability of DEBs to release idarubicin slowly. ConclusionsUsing drug-eluting beads, the maximum-tolerated dose of idarubicin was 10mg per TACE session. Encouraging responses and median time to progression were observed. Further clinical investigations are warranted (NCT01040559).