Use of perfluorochemical emulsions in cancer therapy.

Abstract

Over the past 10 years, the use of perfluorochemical emulsions (PFCE) and carbogen or oxygen breathing has been explored as an adjuvant to radiation therapy and/or chemotherapy in the treatment of solid tumors. The rationale for the use of PFCE and oxygen breathing in this therapeutic setting is that solid tumor masses contain areas of hypoxia which are therapeutically resistant. Since x-rays and many chemotherapeutic agents require oxygen to be maximally cytotoxic and most normal tissues are well-oxygenated, the additional oxygen put in circulation by the PFCE should not increase the normal tissue toxicities produced by the various therapies. The largest body of preclinical work and all of the clinical studies in cancer conducted with PFCE, thus far, have been done with Fluosol-DA, 20%. Oxygen microelectrode studies have confirmed increased oxygenation in previously hypoxic tumor regions after the administration of Fluosol-DA and carbogen breathing. The preclinical studies have shown very positive effects with single dose and fractionated radiation in several rodent solid tumor models. Many widely used anticancer drugs including antitumor alkylating agents and adriamycin are enhanced by PFCE and carbogen breathing for longer time periods (6 h). More recently, several experimental concentrated PFCE preparations have become available and work with these is actively under way in several laboratories. Clinical studies with radiation and four or five chemotherapeutic drugs as single agents have indicated that Fluosol-DA followed by oxygen breathing can be administered safely in a variety of cancer therapeutic settings. Further clinical studies with Fluosol-DA are planned.