Comparison of Stable and Unstable Ethiodized Oil Emulsions for Transarterial Chemoembolization of Hepatocellular Carcinoma: Results of a Single-Center Double-Blind Prospective Randomized Controlled Trial

Summary

This is a prospective single-center double-blind randomized control trial evaluating the safety and efficacy of two embolic mixtures for conventional TACE, one with a stable water-in-oil mixture, and one with an unstable mixture. The study authors enrolled 812 patients over a 5-year period and were blinded to the type of chemoembolic administered in the setting of locoregional therapy for patients with hepatocellular carcinoma.

The embolic technique and type was the premise of this study. Thus, it should be noted that the stable water-in-oil mixture was 50 mg epirubicin / 50 mg lobapatin / 6 mg mitomycin C mixed with 4 mL of solvent (5:1 Iopamidol 300 contrast : Distilled water) and 12 mL ethiodized oil; the unstable water-in-oil mixture was identical except for having 4 mL of distilled water as the solvent (no contrast dilution). This mixture was emulsified for 10 minutes on a test-tube shaker at 1,000 rpm prior to administration.

Once enrolled, patients stayed within that treatment arm but were allowed to undergo additional treatments to include if needed repeat chemoembolization (type not specified by the authors). The study follow-up ended 12-months after enrollment of the last patient. The primary endpoint was overall survival, and the authors saw no significant difference between treatment arms. In addition no difference was observed in tumor response, time to progression, or adverse events. They did note a significant increase in myelosuppression in those patients who received the unstable water-in-oil chemoembolic.

The authors also evaluated the peripheral plasma concentration of epirubicin following TACE in a small subset of patients, finding the peak concentration to be higher in the unstable mixture but with a similar AUC. They also conducted in vitro analyses of solution stability for both epirubicin with solvent (5:1 contrast:water felt most stable and matched specific gravity of ethiodized oil) and epirubicin solution with ethiodized oil (1:3 most stable and uniform).

Commentary

This study is useful given its prospective nature and large size in comparing different techniques for use in conventional TACE. The authors found no significant difference in treatment effects between the two arms. However, they did note differences in myelosuppression and peak epirubicin plasma concentrations with the unstable solvent, suggesting that a more stable chemoembolization solution may help with keeping the drug local in the liver. The in vitro analyses they performed also suggest similar results. Limitations with this study are that it may be hard to duplicate the administered embolic in clinical practice given available medications and contrast agents at one’s institution. Also, the practicality of using a test-tube shaker to achieve a uniform solution may be difficult depending on the clinical scenario. At the very least, this study serves as a baseline for the putative ideal conventional TACE chemoembolic solution, with regard to stability and uniformity of embolics.

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He, M., Zou, R., Wei, W., et al. Comparison of Stable and Unstable Ethiodized Oil Emulsions for Transarterial Chemoembolization of Hepatocellular Carcinoma: Results of a Single-Center Double-Blind Prospective Randomized Controlled Trial. J Vasc Interv Radiol. 2018; 29(8): 1068-1077.

Post Author:
Daniel P. Sheeran, MD
Assistant Professor
Department of Radiology and Medical Imaging
Division of Vascular and Interventional Radiology
University of Virginia