Preliminary results of a study of the synergy of microwave hyperthermia/intravesical chemotherapy in the prevention of recurrent superficial bladder tumours

Objectives : Preliminary clinical studies of the combination of hyperthermi a and intravesical chemotherapy indicated very encouraging results in favou r of multidisciplinary a treatment of recurrent superficial bladder tumours . The authors studied the in vitro and early in vivo effects of this treatm ent. Material and Methods : All intravesical catheter equipped with a microwave antenna was used for hyperthermia in vivo in dogs. The temperature was cont rolled by two intravesical thermocouples and 4 transducers on the bladder w all. 0, 40 or 80 mg of mitomycin were instilled in 60 ml of physiological s aline. Dogs were sacrificed after each one-hour session, and histological intraves ical lesions were defined as grade 0, 1 or 2 corresponding to absence of le sions, or the presence of inflammatory lesions or urothelial lesions, respe ctively. In vitro, the first step consisted of creation of an immortalized tumour ce ll line from a grade II bladder papilloma. This HVT 196 cell line was incub ated between 37 degrees C and 44 degrees C with increasing mitomycin concen trations of 0 to 10 micrograms per ml. The cytotoxicity was measured by the MTT quantitative colourimetric method. Results : In vivo, in 8 dogs, histological analysis of the comparative cyto toxicity of the various treatments confirmed the synergistic effect of heat and mitomycin C. In dogs treated at 45 degrees C, marked urothelial lesions were observed, r egardless of the mitomycin C concentration. The in vitro comparative toxicity study on our cell line showed a much more intense cytotoxic effect with combined treatment than with cytostatic trea tment alone. Expressed as the percentage of cytotoxicity compared to a cont rol cell pool for a concentration of microgram per ml, the temperature rise of the medium between 37 degrees C and 44 degrees C was accompanied by a c ytotoxic effect of 8.4% and 98.41% respectively. Conclusion :A possible clinical application is potentiation of the action o f mitomycin C by hyperthermia in the prevention of recurrent superficial bl adder tumours, achieving increased efficacy and/or a decreased number of in stillations.