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.