MATHEMATICAL-MODELING OF TUMOR-GROWTH IN MICE FOLLOWING ELECTROTHERAPY AND BLEOMYCIN TREATMENT

In treatment of subcutaneous solid tumors in mice locally applied elec trotherapy by direct current and i.v. administered bleomycin were comb ined. The study showed the interaction of both treatments in a way, th at the antitumour effect of both was more than additive when compared to single treatments. The electrotherapy by means of 0.6 mA of one hou r duration, as single treatment significantly delayed tumour growth in comparison to control group (growth delay GD = 6.7+/-1.2 days), where as therapy by 250 mu g bleomycin i.v. injection had only moderate effe ct on tumour growth (GD = 0.5+/-0.2 days). When both treatments were c ombined the tumour growth delay observed was 10.8+/-1.9 days. A model was developed in which the pharmacokinetic model of bleomycin was exte nded and transformed to the level of macroscopic biologically detectab le effect i.e. tumour growth retardation. The data on tumor growth in control group was used to determine parameters of the Gompertz model ( V-0, alpha(upsilon 0) and beta). For modelling of both single treatmen ts the extended Gompertz equation was used. In the case of electrother apy a two component effect had to be introduced in order to obtain sat isfactory fit. The effect of bleomycin on tumour growth was obtained b y introducing the influential parameter which transferred the bleomyci n concentration in tumour tissue obtained from pharmacokinetic model t o the effect on tumour growth.