[Study of the synergy of microwave hyperthermia/intravesical chemotherapy in the prevention of recurrences of superficial tumors of the bladder].

OBJECTIVE

Preliminary clinical studies of the combination of hyperthermia and intravesical chemotherapy indicated very encouraging results in favour of multidisciplinary treatment of recurrent superficial bladder tumours. The authors studied the in vitro and early in vivo effects of this treatment.

METHODS

An intravesical catheter equipped with a microwave antenna was used for hyperthermia in vivo in dogs. The temperature was controlled by two intravesical thermocouples and 4 transducers on the bladder wall. 0, 40 or 80 mg of mitomycin were instilled in 60 ml of physiological saline. Dogs were sacrificed after each one-hour session, and histological intravesical lesions were defined as grade 0, 1 or 2 corresponding to absence of lesions, or the presence of inflammatory lesions or urothelial lesions, respectively. In vitro, the first step consisted of creation of an immortalized tumour cell line from a grade II bladder papilloma. This HVT 196 cell line was incubated between 37 degrees C and 44 degrees C with increasing mitomycin concentrations of 0 to 10 micrograms per ml. The cytotoxicity was measured by the MTT quantitative colorimetric method.

RESULTS

In vivo, in 8 dogs, histological analysis of the comparative cytotoxicity 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, regardless 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 treatment alone. Expressed as the percentage of cytotoxicity compared to a control cell pool for a concentration of 1 microgram per ml. the temperature rise of the medium between 37 degrees C and 44 degrees C was accompanied by a cytotoxic effect of 8.4% and 98.41% respectively.

CONCLUSIONS

A possible clinical application is potentiation of the action of mitomycin C by hyperthermia in the prevention of recurrent superficial bladder tumours, achieving increased efficacy and/or a decreased number of instillations.