Distribution of adriamycin in mice under conditions of local hyperthermia which improve systemic drug therapy.

Local tumor hyperthermia (LTH) (43 degrees C for 60 minutes) enhanced the effectiveness of Adriamycin (ADR) (10 mg/kg iv) administered systemically against the 16C mouse mammary adenocarcinoma. LTH was produced by the local application of 2450 MHz microwaves to sc implanted tumors. During LTH the intratumor temperature uniformity was +/- 0.5 degrees C and the rectal temperatures were 36 degrees C--38 degrees C. The simultaneous application of LTH and ADR resulted in tumor growth delays which were greater than those expected from the addition of individual treatments. Enhanced effectiveness of these treatments did not occur if the two treatments were separated by 4 hours. Cures were observed only in the treatment groups that received drug and heat simultaneously. Measurements of the tissue distribution of ADR and its metabolites using 14C-ADR indicated that the uptake of radioactivity in the heated tumors was not increased by LTH. A greater percentage of the radioactivity in heated tumors was recovered as ADR metabolites and correspondingly less radioactivity was recovered as unchanged ADR.