Thermostability of Cytostatic Drugs in Vitro and Thermosensitivity of Cultured Human Lymphoblasts Against Cytostatic Drugs

Abstract

The interaction of hyperthermia and antineoplastic therapy has attracted new interest recently. Experimental in vitro and in vivo studies showed an increased cytotoxic effect on malignant cells when hyperthermia was combined either with radiation therapy or chemotherapy (Hahn 1979; Herman et al. 1982; Kai et al. 1986; Mini et al. 1986; Overgaard 1976; Overgaard and Overgaard 1972). A large variety of cytostatic drugs are effective as antineoplastic agents, but only a few of them have yet been tested under hyperthermic conditions. Therefore 16 different cytostatic drugs were tested to find out whether they are suitable for further clinical studies, especially in combination with the application of regional hyperthermia. At first the thermostability of these drugs was tested in vitro. Then the influence of hyperthermia on the cytotoxic efficiency of the drugs was examined. Furthermore, the lowest temperatures at which an increased cytotoxicity occurred were tested. Since the application of regional hyperthermia can increase wholebody temperature to 39° C, it is important to know whether there are cytotoxic drugs which show an increased cytotoxicity only at temperatures above 39° C. These drugs would not increase systemic side effects such as bone marrow toxicity. Increased side effects could otherwise be limiting factors of the treatment. Drugs ideal for combination with regional hyperthermia develop their increased activity only in the heated tumor region.