Chemoembolization of liver cancer with doxorubicin-loaded CalliSpheres microspheres: plasma pharmacokinetics, intratumoral drug concentration, and tumor necrosis in a rabbit model

The purpose of this work was to investigate the plasma pharmacokinetics, intratumoral drug concentration, and tumor necrosis after transarterial chemoembolization (TACE) with doxorubicin-loaded CalliSpheres microspheres (CSMs). Sixty rabbits with liver VX2 tumors were assigned into five groups of 12 rabbits each, which received 4 mg of doxorubicin via intravenous injection (IV group), hepatic arterial infusion (IA group), conventional TACE (cTACE group), CSM-TACE (CSM low-dose group), and 8 mg of doxorubicin via CSM-TACE (CSM high-dose group), respectively. Doxorubicin concentrations in plasma, tumor, and adjacent hepatic parenchyma were measured at various timepoints after treatment, and tumor necrosis percentage and liver enzymes were also assessed. The peak plasma concentration of doxorubicin was significantly lower in the three TACE groups compared to IV and IA group (P < 0.05), while doxorubicin concentrations in tumor and adjacent hepatic parenchyma were higher in the two CSM groups compared with IV, IA, and cTACE groups at 3 days and 7 days after treatment (P < 0.05). The percentages of tumor necrosis at 3 and 7 days after treatment were significantly higher in three TACE groups (all higher than 50%) compared with IV group and IA group (both lower than 25%) (P < 0.05), and the highest tumor necrosis percentage was achieved in CSM high-dose group. The three TACE groups showed transient increases in transaminases levels after treatment, in which the peak transaminases levels were significantly lower in the two CSM groups than those in cTACE group (P < 0.05). CSM achieves an effective delivery of doxorubicin into liver cancer. High-dose doxorubicin improves tumoricidal capacity while not impairing the safety of the doxorubicin-loaded CSM.