Pharmacokinetics, Safety, and Efficacy of Chemoembolization with Doxorubicin-Loaded Tightly Calibrated Small Microspheres in Patients with Hepatocellular Carcinoma.

Abstract

This study examines safety, efficacy, and pharmacokinetics of chemoembolization with loadable microspheres ≤100μm for hepatocellular carcinoma. A pilot safety study was performed in 19 patients with size and dose escalation and then 52 patients were enrolled prospectively and randomly assigned to chemoembolization with TANDEM™ loaded with 150 or 100mg of doxorubicin. The mean diameter of the tumors was 7.28±2.09cm (range 4-12) and distribution dominant/multiple 51.9/48.1%. Child A/B distribution was 32/20 (61.5/38.5%) and etiology HBV/HCV/HBV/HCV-hemochromatosis was 61.6/9.6/9.6/15.4%. Twenty-five patients were assigned in the low and 27 in the high loading group. There was 1.92% thirty-day mortality due to lesion rupture. Biliary damage was seen in 3 patients (5.7%) in the high loading. Mean maximum plasma concentration of doxorubicin C max±SD was 284.9±276.2ng/mL for the high and 108.5±77.6ng/mL for the low loading (p<0.001). According to m-RECIST overall objective response after two sessions reached 61.22 and 63.82% at 6months. Notably, complete target lesion response (CR) after the second session was observed in 28.57% and maintained in 23.40% at 6months. No statistical differences in the local response rates were observed between the two loading groups. Overall survival (OS) at 6months, 1 , 2, and 3 years was 98.08, 92.3, 88.46, and 82.6%, respectively. OS and Progression-Free Survival did not demonstrate statistical significance between the two loading groups. Initial evidence shows that (a) TANDEM™ achieves high rates of local response and mid-term survival, (b) high loading provides no clinical benefit and is associated with biliary toxicity.