Lobar versus Selective Conventional Transcatheter Arterial Chemoembolization: An Interim Report of a Prospective Pharmacokinetic Study

Purpose: To compare the pharmacokinetic (PK) profiles of doxorubicin (DOX) and its metabolite doxorubicinol (DOXOL) after conventional transarterial chemoembolization (cTACE) using lobar or segmental injection

Materials and Methods: This interim report of an ongoing single-site, prospective trial included 22 patients with hepatocellular (n = 19), cholangiocellular carcinoma (n = 1), and neuroendocrine tumor metastases (n = 2) who were treated with lobar (n = 7) or selective (n = 15) cTACE defined by catheter placement (May 2016 to October 2017). cTACE used 50 mg of DOX/10 mg mitomycin-C emulsified with Lipiodol followed by Embospheres. Peripheral blood was sampled after cTACE (5, 10, 20, and 40 minutes; 1, 2, 4, and 24 hours; and 3–4 weeks) to measure drug concentrations by standard noncompartmental analysis. Follow-up included cross-sectional imaging and adverse events (AEs) recorded 3 to 4 weeks post-TACE. Statistics included Pearson coefficient, Mann-Whitney, and chi-squared test.

Results: Mean age was 62 ± 9.21 years, and 19 patients were males. Hepatocellular carcinoma were Barcelona Clinic Liver Cancer (BCLC) stage A in 4, B in 11, and C in 4 patients. According to 3DqEASL criteria available in 20 of 22 patients, complete and partial response were achieved in 1 and 6 and stable and progressive disease in 8 and 5 patients, respectively. Full DOX dose was given in 17 of 22 patients. DOX concentration peaks occurred earlier (median Tmax, 0.25 [0.13–0.98] vs 0.59 [0.12– 1.72 hours]) and were higher after lobar than selective cTACE (mean dose normalized Cmax, 4.74 ± 3.6 vs 3.08 ± 3.11 ng/mL/mg) and in nonresponders compared with responders (P = 0.022). The DOX area under the curve was significantly larger in patients with higher enhancing tumor volume (P = 0.009) or enhancing tumor burden (P = 0.033) on baseline imaging. DOXOL was similar, but DOX concentrations were higher after lobar than selective cTACE at each timepoint but without statistical significance. Both DOX and DOXOL were undetectable 3 to 4 weeks after cTACE. AEs were rare but occurred more often after lobar cTACE (fever, P = 0.040; abdominal pain, P = 0.030).

Conclusions: The preliminary results of this prospective trial show a consistent trend suggesting higher systemic chemotherapy exposure and toxicity after lobar compared with selective cTACE. If confirmed in the complete cohort, these findings may lead to a paradigm shift in intraarterial therapy in favor of selective cTACE as a safe and efficient treatment for patients with liver cancer.