How Many Days of Doxorubicin Delivery Can DEE Transarterial Chemoembolization Provide?

Drug-eluting embolic (DEE) transarterial chemoembolization agents are able to deliver doxorubicin to targeted tissues even 80 days after chemoembolization, according to a study published in the June JVIR.

Hadrien D’inca, PhD, and colleagues, examined 4 patients with hepatocellular carcinoma who underwent surgical resection 57, 79, 80, and 105 days after being treated with doxorubicin DEE chemoembolization. The patients were treated consecutively between January 2012 and October 2013.

Analysis of the resected tissue revealed that doxorubicin concentration within the DEE particles, which initially had a DEE doxorubicin concentration of 37.5 mg/mL, significantly decreased as time passed. After 57 days, the particles still had 17.2% of their initial loaded concentration, whereas after 79 days and 80 days the particles maintained 16.6% and 9% of their initial loaded concentration, respectively. After 105 days, doxorubicin was undetectable.

The investigators also assessed drug elution by accounting for the number of embolic particles aggregated. They found that embolic particle aggregation inside vessel lumina was linked with slower doxorubicin elution and higher tissue concentration when the number of aggregated DEE agents rose.

“This phenomenon could be explained by a faster doxorubicin release from DEE particles in a free drug environment compared with a saturated drug environment. In addition, the origin of the cluster effect may be multifactorial,” the study’s authors wrote.

The researchers acknowledged several limitations to the study, including the small sample size and the inability to precisely locate tissue samples within the tumors, which is a consequence of the retrospective design.

Even with these limitations, the study is valuable for its original data on doxorubicin quantification inside DEE agents and in surrounding tissue over long periods of time following chemoembolization, the authors noted. “Moreover, aggregation of DEE particles inside vessel lumina was shown to impact doxorubicin kinetics, with a slower elution and a higher drug tissue concentration around multiple aggregated DEE particles,” they concluded.

Reference

D’inca H, Piot O, Diebold M, et al. Doxorubicin drug-eluting embolic chemoembolization of hepatocellular carcinoma: study of midterm doxorubicin delivery in resected liver specimens. JVIR. 2017;28(6):804–810.