Fractionated thermochemotherapy in vivo of a C3H mouse mammary carcinoma

Abstract

The interaction between fractionated heat treatment and fractionated drug treatment with cyclophosphamide (CTX) was investigated in a transplantable C3H mouse mammary carcinoma inoculated into the hind leg of C3D2F1/Bom mice. A tumour core temperature of 43.5 +/- 0.1 degrees C was achieved by immersing the tumour-bearing leg into a water bath thermostatically maintained at 43.7 +/- 0.1 degrees C. CTX was administered i.p. using the maximum tolerated dose (MTD) (LD 1%) for single fraction treatment (100 mg/kg) as the maximum fraction dose. For combined treatment CTX was given 15 min prior to heating. The endpoint was the time to reach a tumour volume of 5 times the volume at first treatment. Specific growth delay was used as effect parameter. In dose-effect experiments using total treatment time at 43.5 degrees C as dose parameter, drug enhancement ratio (DER) was determined as the ratio of the slope of the dose-effect curve for MTD of CTX plus heat to the slope of the curve for heat alone. In dose-effect experiments using total CTX dose as dose parameter, thermal enhancement ratio (TER) was determined as the ratio of the slope of the dose-effect curve for CTX plus 43.5 degrees C for 30 min to the slope of the curve for CTX alone. The regimens investigated were single fraction treatment and 3 and 5 fractions with time intervals of 3 and 5 days. For single fraction treatment DER was 1.4 +/- 0.1 and TER 2.3 +/- 0.2. The drug sensitization of the effect of heat treatment tended to increase with increasing number of fractions.(ABSTRACT TRUNCATED AT 250 WORDS)