Arterial-injection chemotherapy for hepatocellular carcinoma using monodispersed poppy-seed oil microdroplets containing fine aqueous vesicles of epirubicin. Initial medical application of a membrane-emulsification technique.

Abstract

Iodized poppy-seed oil (IPSO) has a property of depositing itself selectively in the cells of hepatocellular carcinoma (HCC). A mixture of anticancer agents and IPSO has been used widely because IPSO accumulates in tumors, but its usefulness appears limited because the anticancer agents become separated easily from IPSO and do not remain in the tumor. The authors prepared a long term inseparable, water-in-oil-in-water emulsion (W/O/W) for use in arterial-injection therapy for patients with HCC and evaluated its clinical usefulness. The W/O/W was prepared by a membrane-emulsification technique using a controlled pore glass with 10.6-microns pores. From December 1992 to January 1994, the W/O/W containing 8-60 mg of epirubicin was applied to the hepatic arterial-injection therapy for 21 patients with HCC to determine its antitumor and side effects. After arterial infusions with W/O/W, an evident antitumor effect was observed in all 13 patients treated with W/O/W containing 40 mg or more of epirubicin with or without gelatin-sponge particles used simultaneously. In the group treated with the W/O/W containing a high dose (40 mg or more) of epirubicin, even though the gelatin-sponge particles were not used, tumor size was reduced in six of seven patients, and a 50% or greater decrease of initial alpha-fetoprotein (AFP) levels within 14 days was observed in all four patients who showed abnormal levels of serum AFP before treatment. One partial necrosis and two complete necroses of three resected tumors were confirmed histopathologically. Fever (in all patients), nausea (in two), pain in the right upper quadrant of the abdomen (in two), and slight cough (in one) were noted as minor side effects. To the authors' knowledge, this is the first clinical trial using this emulsion prepared by the membrane-emulsification technique. Emulsification using a fine-pore glass membrane of equal pore size (i.e., controlled-pore glass membrane) is a new technique for preparing lipid microdroplets of equal size (monodispersed) containing aqueous fine microdroplets to form W/O/W: This technique of chemoembolization can be used to treat patients with HCC.