Thermochemotherapy in vivo of a C3H mouse mammary carcinoma: Thermotolerant tumours

Abstract

The ability of cyclophosphamide (CTX) and mitomycin C (MMC) to modify the expression of thermotolerance in vivo at 43.5°C was investigated in a transplantable C3H mouse mammary carcinoma grown s.c. in feet of C3D2Fl/Bom mice. Dose-effect curves subjected to linear regression analysis were constructed for single-fraction treatment and for a second treatment 24 h after a priming heat treatment of 43.5°C for 30 min. Tumour volume doubling time during regrowth showed no significant variation among treatment groups, justifying the use of tumour growth time as effect parameter. Thermotolerance ratio for heat alone was 11.6±2.3. Drug enhancement ratio in thermotolerant tumours was 6.2± 1.4 for CTX (100 mg/kg) and 3.5±0.9 for MMC (3 mg/kg). These values are about 4 and 3 times larger than the corresponding enhancement ratios found for previously untreated tumours. Thermotolerance ratio for thermochemotherapy was 2.6±0.3 for CTX and 4.4±0.7 for MMC, i.e. the degree of thermotolerance was substantially reduced by both drugs, but not completely overcome. Thermal enhancement ratio for CTX and MMC was about equally large in thermotolerant and previously untreated tumours. Thermotolerant tumours showed a tendency for increased resistance to drug treatment alone. Both CTX and MMC may be used clinically to reduce the expression of thermotolerance, particularly in situations with inhomogeneous heating and short fractionation intervals.

Key Words:

• hyperthermia
• thermotolerance
• thermochemotherapy
• cyclophosphamide
• mitomycin C.