A Phase I/II Trial of Chemoembolization for Hepatocellular Carcinoma Using a Novel Intra-Arterial Drug-Eluting Bead

Background & Aims: To assess the safety and efficacy of transarterial chemoembolization (TACE) using doxorubicin-eluting beads (DEB) for hepatocellular carcinoma (HCC). Methods: Patients with incurable HCC and Child-Pugh class A cirrhosis were considered eligible for this phase I/II trial. Two courses of TACE using DEB were given at an interval of 2 months, and tumor response was assessed by computerized tomography scan. The phase I trial was a dose-escalating study starting from 25 mg to 150 mg doxorubicin in cohorts of 3 patients. The 150-mg doxorubicin dose was used for the phase II study. Primary end points were treatment-related complications and deaths. Secondary end points included tumor response and pharmacokinetics of doxorubicin. Results: In the phase I study involving 15 patients, no dose-limiting toxicity was observed for up to 150 mg doxorubicin, which was used for 20 patients in the phase II study. The pharmacokinetic study showed a low peak plasma doxorubicin concentration (49.4 ± 23.7 ng/mL), and no systemic toxicity was observed. The treatment-related complication rate was 11.4%. There was no treatment-related death. Among 30 patients who completed 2 courses of TACE, the partial response rate and the complete response rates were 50% and 0%, respectively, by response evaluation criteria in solid tumors (RECIST) criteria at computerized tomography scan 1 month after the second TACE. By modified RECIST criteria, taking into account the extent of tumor necrosis, 19 (63.3%) patients had a partial response and 2 (6.7%) had a complete response. Conclusions: This study shows that TACE using DEB is a safe and effective treatment for HCC, supporting a phase III randomized trial to compare this novel treatment with conventional TACE using doxorubicin-Lipiodol emulsion.