4'-Epi-doxorubicin 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 right 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 or 43 degrees C) was carried out. Mice were treated with EP and/or HT in 1, 2 or 3 doses at 8 day intervals; in the case of 3 HT treatments EP was administered before the first or before each HT session (same EP total dose). When EP was given alone, in 1 or 2 fractions, results showed a clear dose-response relationship: tumor growth delay depended on the total dose only. Combining different EP single doses and 1 HT treatment (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 treatment.