4'-EPIDOXORUBICIN AND HYPERTHERMIA IN A MURINE MAMMARY-CARCINOMA - INFLUENCE OF THE DOSE AND FRACTIONATION

Our aim was to analyse the dose-response rate of 4'epi-doxorubicin (EP ) alone and of EP combined with hyperthermia (HT) treatments in tumor- bearing mice. A spontaneous mammary carcinoma, transplanted into the r ight foot of female hybrid (C3H/RIxDBA/2J) mice, was used. EP (from 5 to 30 mg/kg) was administered i.p. and local HT (45-60 minutes at 42 o r 43 degrees C) was carried out. Mice were treated with EP and/or HT i n 1, 2 or 3 doses at 8 day intervals; in the case of 3 HT treatments E P was administered before the first or. before each HT session (same E P total dose). When EP was given alone, in 1 or 2 fractions, results s howed a clear dose-response relationship: tumor growth delay depended on the total dose only. Combining different EP single doses and I HT t reatment (43 degrees C), an additive effect and perhaps a synergistic effect at the highest doses was observed Among all tested combinations , the best results were observed combining 3 HT with only 1 EP treatme nt.