Studies on fractionated hyperthermia in experimental animal systems II. Response of murine tumors to two or more doses.

The effect of multiple hyperthermia and the kinetics of thermal resistance were studied in experimental murine tumors. A spontaneous C3Hf mouse mammary carcinoma, MCa had a chemically-induced fibrosarcoma, FAa-1, were used. Assay methods included determination of the TCD50, i.e., the treatment time to yield a tumor control in half the treated animals and TG (tumor growth) time analysis, i.e., the time required for a tumor to reach a given size after first treatment. After equal dose fractions the TCD50 of MCa increased with increasing overall treatment time. This increase was most predominant when treatments were given with a time interval of one day. Isoeffect curves for the MCa were comparable to those for normal tissue damage (foot reaction), which was reported in the first part of this series of communications. The kinetics of thermal resistance in the MCa was compared with that in FSa-I since the fractionated hyperthermia for the FSa-I was reported to have resulted in an appreciable therapeutic gain. The magnitude of thermal resistance was far greater in the MCa than in the FSa-I, although the kinetics of thermal resistance was similar in both tumors; i.e., (a) the resistance reached a maximum in 24 hours after treatment and then decayed slowly, and (b) the development of thermal resistance increased with increasing initial dose. The thermal resistance in these tumors appeared to be greater than that in animal feet.