Comparing Stable vs Unstable Emulsions for Chemoembolization

Researchers have found that stable and unstable water-in-oil (W/O) emulsions are equally effective for chemoembolization, though stable emulsions lead to less myelosuppression and a more favorable pharmacokinetic profile.

The types of ethiodized oil emulsions or mixing steps have not been described in most clinical studies examining sustained drug delivery, and no prospective trial has, to the authors’ knowledge, compared chemoembolization with stable and unstable W/O emulsions.

As a result, the researchers conducted a prospective, single-center, double-blind randomized phase III trial of 812 patients with inoperable hepatocellular carcinoma (HCC). The patients were randomized to receive either stable emulsion (402 patients) or unstable emulsion (410 patients). The same protocol was used to prepare the two emulsions, with the exception that different solvents were used for chemotherapy agents, including epirubicin, lobaplatin, and mitomycin C.

The stable emulsion arm used a solvent that was contrast medium and distilled water, while the unstable emulsion arm used distilled water. Overall survival was the primary endpoint, and  time to progression, tumor response, adverse events, and plasma epirubicin concentrations comprised the secondary endpoints.

Results revealed that stable emulsions did not occur until 1 day in vitro. On the other hand, unstable emulsions, with a lower peak plasma concentration in vivo, after 10 minutes demonstrated rapid separation of the oil and aqueous phases.

Patients in the stable emulsion arm had a median overall survival of 17.7 months, whereas those in the unstable arm had 19.2 month overall survival. There were no differences in time to progression, tumor response, and adverse events. However, patients in the unstable arm had significantly more severe and frequent myelosuppression.

“In summary, emulsion stability in vitro may not be predictive of emulsion stability in vivo. This study failed to demonstrate a superiority of a stable emulsion over an unstable emulsion regarding tumor response or overall survival, but patients in the stable emulsion arm had a lower degree of myelosuppression and a favorable pharmacokinetic profile,” the researchers concluded.


He MK, Zhou RH, 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. 3 July 2018. Online ahead of print. doi: