LOCAL HYPERTHERMIC TREATMENT DOES NOT ENHANCE MITOXANTRONE EFFECTIVENESS FOR RESPONSES OF A RAT SOLID TUMOR REGROWING AFTER IRRADIATION

Tumours regrowing after irradiation may respond differently to chemo-h yperthermia as compared to non-irradiated tumours. In this study, the efficacy of combined treatment of previously irradiated tumours with m itoxantrone and local hyperthermia (HT) was investigated. Rat R-1 tumo urs were irradiated with dose fractions of 5 Gy X-rays applied on 4 co nsecutive days. Animals were retreated with mitoxantrone (5 mg/kg i.p. ), HT (1 h at 43 degrees C) or mitoxantrone + HT (3-h interval) on day 9 after the start of irradiation when tumour volumes were decreasing, or on day 16 when tumour volumes were increasing again. Pharmacokinet ics were studied in relation to tumour cell survival and tumour growth delay. No HT-induced changes in the pharmacokinetics of mitoxantrone were observed. The data on clonogenic survival correlated well with th ese findings and combined treatments were not more effective than mito xantrone alone. In the treatment schedule applied, HT did not induce p harmacokinetic changes in irradiated tumours leading to an enhanced cy totoxicity of mitoxantrone. The HT-enhanced effectiveness of the drug observed in non-irradiated rumours is much less in pre-irradiated tumo urs. Responses of regrowing tumours to combined chemo-hyperthermia dep end in a complex way on the stage of regrowth and On the treatment sch edule.