Pharmacokinetic study comparing doxorubicin concentrations after chemoembolization or intravenous administration in dogs with naturally occurring nonresectable hepatic carcinoma

Abstract

Abstract Background Chemoembolization is a viable treatment option for patients with nonresectable hepatic carcinoma (HC) and may allow delivery of chemotherapeutic drugs with decreased systemic toxicity. Hypothesis/Objective Compare the serum concentrations of doxorubicin after chemoembolization or IV administration in the same patient. We hypothesized that locoregional delivery may result in increased tumor chemotherapeutic drug concentrations, reflected by decreased measurable serum drug concentrations. Adverse hematological events were hypothesized to be decreased after locoregional delivery. Animals Seventeen client‐owned dogs with incompletely resectable HC. Methods Prospective, single‐arm clinical trial. Drug‐eluting bead transarterial chemoembolization was performed to varying levels of blood flow stasis (NO STASIS, STASIS). Intravenous doxorubicin (IVC) subsequently was administered in selected patients. Systemic exposure was quantified by area under the serum doxorubicin concentration time curve (AUC), maximum serum doxorubicin concentration (Cmax), and time doxorubicin was last above the limit of quantitation (Tlast). Nadir test results after treatments were used to evaluate adverse hematological events. Results Thirteen NO STASIS treatments, 15 STASIS treatments, and 9 IVC treatments were performed. Maximum serum doxorubicin concentration, AUC, and Tlast were significantly lower when comparing NO STASIS or STASIS to IVC treatments. Of the patients with nadir results available, no adverse hematological events were observed after NO STASIS or STASIS treatments. Two patients developed adverse hematological events after IVC treatment. Conclusions/Clinical Relevance Drug‐eluting bead transarterial chemoembolization offers a viable treatment option for patients with incompletely resectable HC with the potential for increased local tumor doxorubicin concentrations, decreased systemic chemotherapeutic exposure, and fewer adverse hematological events.

Keywords

• chemotherapy
• hepatic disease
• hepatocellular carcinoma
• interventional radiology