Selected Preclinical and First Clinical Experiences with Magnetically Targeted 4’-Epidoxorubicin in Patients with Advanced Solid Tumors

Abstract

Although site-specific direction of drugs within the organism would benefit the patient in many diseases, active drug-targeting has clinically not yet been possible. To overcome some of the problems associated with active drug-targeting, we have developed a magnetic fluid to which drugs, cytokines, DNA-fragments, other molecules and (cytokine-induced killer) cells can be chemically bound so that those agents could be directed and concentrated within the organism by high-energy magnetic fields. In the first part of this chapter, the making and specifications of the ferrofluid are described. In the second part, our experiences with studies of various concentrations of the magnetic fluid in immunosuppressed nude mice, that had been xenotransplanted with human tumors with regard to subjective and objective tolerance are reported. Magnetic drug-targeting, utilizing small amounts of the ferrofluid as a vehicle to concentrate epirubicin locally in tumors is also described. In the third part, a phase-I clinical trial utilizing this approach in patients with advanced and unsuccessfully pretreated cancers or sarcomas is described, followed by a discussion of the specific results in narrow and broad context.