Hepatic Arterial Embolization with Doxorubicin-Loaded Superabsorbent Polymer Microspheres in a Rabbit Liver Tumor Model

Abstract

Objectives To study the pharmacokinetic profile after hepatic arterial embolization with superabsorbent microspheres (QuadraSpheres) loaded with doxorubicin. Materials and Methods Rabbits with hepatic VX2 tumors were treated with intra-arterial administration of QuadraSpheres loaded with doxorubicin, or transarterial chemoembolization (TACE) using doxorubicin, Lipiodol and Embospheres, or hepatic arterial infusion (HAI) of doxorubicin. Tumor specimens were evaluated by fluorescence microscopy, and plasma and tumor concentrations of doxorubicin were measured. Results The peak plasma concentration of doxorubicin was lower in the QuadraSphere group (309.9 ng/ml) than in the HAI (673.4 ng/ml) or TACE (360.5 ng/ml) groups, suggesting higher tumor retention in the QuadraSphere group. Intratumoral doxorubicin levels declined to negligible levels at 1 and 3 days after treatment, respectively in the HAI and TACE groups. In the QuadraSphere groups, intratumoral doxorubicin level declined after day 1, but was still detectable at 14 days after treatment and was higher than that in the other groups at 1, 3, and 7 days. Intratumoral doxorubicin fluorescence was detected at all time points in the QuadraSphere group, but only at 1 day after treatment in the TACE group. Conclusions Hepatic arterial administration of doxorubicin-loaded QuadraSpheres enables the sustained release of doxorubicin to hepatic tumors.

Superselective Chemoembolization of HCC: Comparison of Short-term Safety and Efficacy between Drug-eluting LC Beads, QuadraSpheres, and Conventional Ethiodized Oil Emulsion

“…These new vehicles may offer the opportunity to implement a higher level of standardization to HCC treatment (1). Previous studies have shown that TACE with drug-eluting microspheres has an improved pharmacokinetic profile and results in effective tumor killing in both preclinical animal models and clinical studies in humans (4)(5)(6)(7)(8). The PRECISION V randomized trial did not reach its primary end point of improved objective response at 6 months, but did identify relative benefit of using drugeluting microspheres to achieve a higher response rate in high-risk patients and lower toxicity overall (8).…”

“…Specifically, the advantages of higher response rates in high-risk patients, lower hepatic and with positively charged moieties in drugs such as doxorubicin by an ion-exchange mechanism and allow loading of the drug from dilute solutions. Use of drug-eluting microspheres for TACE leads to high and sustained intratumoral doxorubicin concentrations, as well as decreased systemic drug levels and toxicity (3)(4)(5)(6)(7)(8).…”

Chemoembolization of hepatocellular carcinoma with HepaSphere™

“…Unlike the other microspheres HepaSphere is the only loadable microsphere that is more elastic and has a better contact with the vessel wall of the tumor causing necrosis [9,10,11,12]. HepaSphere loading and elution occurs in the same time window for the two smaller available sizes ranging from 15 min to 2 h and 1 h to 14 days, respectively [13]. Animal studies with HepaSphere have shown that bland HepaSphere presents lower cancer cell killing effect compared with HepaSphere loaded with doxorubicin [14].…”

Coadministration of telaprevir and transcatheter arterial chemoembolization in hepatitis C virus-associated hepatocellular carcinoma

“…Although such interactions remain theoretical, they are possible as systemic concentrations of doxorubicin can be identified following TACE. For example, in one study using a rabbit liver tumor model, plasma concentration of doxorubicin after TACE was as high as 360.5 ng/mL [18] . In a phase 2 study designed to establish the efficacy and safety of drug eluting beads loaded with doxorubicin for the TACE treatment of HCC patients, doxorubicin Cmax and AUC were 78.97 ± 38.3 ng/mL and 662.6 ± 417.6 ng/mL respectively [19] .…”