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

Background. 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 IPS O accumulates in tumors, but its usefulness appears limited because th e anticancer agents become separated easily from IPSO and do not remai n 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 f or patients with HCC and evaluated its clinical usefulness. Methods. T he W/O/W tvas prepared by a membrane-emulsification technique using a controlled pore glass with 10.6-mu m pores. From December 1992 to Janu ary 1992, the W/O/W containing 8-60 mg of epirubicin was applied to th e hepatic arterial-injection therapy for 21 patients with HCC to deter mine its antitumor and side effects. Results. After arterial infusions with W/O/W, an evident antitumor effect was observed in all 13 patien ts treated with W/O/W containing 40 mg or more of epirubicin with or w ithout gelatin-sponge particles used simultaneously, In the group trea ted with the W/O/W containing a high dose (40 mg or more) of epirubici n, 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 trea tment, One partial necrosis and two complete necroses of three resecte d tumors were confirmed histopathologically. Fever (in all patients), nausea (in two), pain in the right upper quadrant of the abdomen (in t wo), and slight cough (in one) were noted as minor side effects. Concl usions. To the authors' knowledge, this is the first clinical trial us ing this emulsion prepared by the membrane-emulsification technique. E mulsification using a fine-pore glass membrane of equal pore size (i.e ., controlled-pore glass membrane) is a new technique for preparing li pid microdroplets of equal size (monodispersed) containing aqueous fin e microdroplets to form W/O/W. This technique of chemoembolization can be used to treat patients with HCC.