Improved stability of lipiodol–drug emulsion for transarterial chemoembolisation of hepatocellular carcinoma results in improved pharmacokinetic profile: Proof of concept using idarubicin

Objectives: To investigate the relationship between the improved stability of an anticancer drug–lipiodol emulsion and pharmacokinetic (PK) profile for transarterial chemoembolisation (TACE) of hepatocellular carcinoma (HCC). Methods: The stability of four doxorubicin– or idarubicin–lipiodol emulsions was evaluated over 7 days. PK and clinical data were recorded after TACE with the most stable emulsion in eight unresectable HCC patients, after institutional review board approval. Results: The most stable emulsion was the one that combined idarubicin and lipiodol (1:2 v:v). At 7 days, the percentages of aqueous, persisting emulsion and oily phases were 50-0-50, 33-0-67, 31-39-30, and 10-90-0 for the doxorubicin–lipiodol (1:1 v:v), doxorubicin–lipiodol (1:2 v:v), idarubicin–lipiodol (1:1 v:v), and the idarubicin–lipiodol (1:2 v:v) emulsion, respectively. After TACE, mean idarubicin C_max and AUC_0-24h were 12.5 ± 9.4 ng/mL and 52 ± 16 ng/mL*h. Within 24 h after injection, 40 % of the idarubicin was in the liver, either in vessels, tumours, or hepatocytes. During the 2 months after TACE, no clinical grade >3 adverse events occurred. One complete response, five partial responses, one stabilisation, and one progression were observed at 2 months. Conclusion: This study showed a promising and favourable PK and safety profile for the idarubicin–lipiodol (1:2 v:v) emulsion for TACE. Key Points: • Transarterial chemoembolisation (TACE) regimens that improve survival in hepatocellular carcinoma are needed. • Improved emulsion stability for TACE resulted in a favourable pharmacokinetic profile. • Preliminary safety and efficacy data for the idarubicin–lipiodol emulsion for TACE were encouraging.