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

PURPOSE: This study examines safety, efficacy, and pharmacokinetics of chemoembolization with loadable microspheres ≤100 µm for hepatocellular carcinoma. MATERIALS AND METHODS: 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 100 mg of doxorubicin. RESULTS: The mean diameter of the tumors was 7.28 ± 2.09 cm (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 ± 276.2 ng/mL for the high and 108.5 ± 77.6 ng/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 6 months. Notably, complete target lesion response (CR) after the second session was observed in 28.57 % and maintained in 23.40 % at 6 months. No statistical differences in the local response rates were observed between the two loading groups. Overall survival (OS) at 6 months, 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. CONCLUSION: 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.

Safety profile of sequential transcatheter chemoembolization with DC Bead™: results of 237 hepatocellular carcinoma (HCC) patients.

INTRODUCTION: Complications of chemoembolization performed with DC Bead(™) loaded with doxorubicin (DEBDOX) of diameters 100-300 µm and 300-500 µm are presented in this paper. These diameters are currently the smallest available in drug-eluting technology. METHODS: Included are 237 patients who were treated with sequential DEBDOX with doxorubicin loaded at 37.5 mg/ml of DC Bead. The National Cancer Institute Common Terminology Criteria for Adverse Events (version 3.0) were used to categorize complications. RESULTS: Thirty-day mortality was 1.26% (3/237). Incidence of grade 5 complications was 1.26% (3/237). Overall, grade 4 complications resulted in 5.48% (13/237) (irreversible liver failure, cholecystitis). Grade 2 liver function deterioration developed in 10 patients (4.2%). Cholecystitis/grade 2 and 4 incidents were observed in 3.6-5.06% across sessions (overall 13 patients; 5.48%). Postembolization Syndrome (PES) grade 1 or 2 was observed in up to 86.5%; however, grade 2 was observed in 25-42.19% across treatments. Pleural effusion was seen in eight patients (overall 3.37%; grade 1 in 1.8-3.7% across treatments; grade 3 in 0.42%). Grade 1 procedure-related laboratory pancreatitis was seen in 0.45%, and grade 2 gastrointestinal bleeding was seen in 0.84%. Procedure-associated skin erythema/grade 1 was seen in 0.84%. There was no correlation of liver failure or transient liver function deterioration with the diameter of the beads (p = 0.25-0.37 and p = 0.14-0.89, respectively). Stratifying with the diameter of the beads correlation values was: for cholecystitis (p = 0.11-0.96 across treatments), PES (p = 0.35-0.83), temporary/grade 1 elevation of liver enzymes (p = 0.002-0.0001), and bilirubin (p = 0.04-0.99). CONCLUSIONS: DEBDOX chemoembolization is safe and small calibres do not result in increased complication rates compared with results of series using larger diameters of beads.