Development of thermotolerance in a human melanoma xenograft.

The kinetics of thermotolerance in a human malignant melanoma grown in athymic mice (BALB/c/nu/nu/BOM) was studied. Local hyperthermia was given by immersing the tumor-bearing leg of the mice into a thermostatically regulated water bath. The tumors were exposed to a priming heat dose of 42.5 degrees for 30 min and, at different fractionation intervals, to graded heat doses at 42.5 degrees. Tumor volumetric tripling time, i.e., the time from the day the first treatment was given to the day the tumor volumes had reached 3 times the initial volumes, was used as measure of response. The thermotolerance ratio, i.e., the ratio of the slopes of the dose-response curves (tumor volumetric tripling time versus heating time) for preheated tumors and single-heated tumors, was used as the measure of thermotolerance. Thermotolerance developed rapidly; the thermotolerance ratio reached a maximum of 4.9 +/- 0.3 (S.E.) at 16 hr and then decayed slowly to 1.1 +/- 0.1 at 168 hr (7 days). Implications of the present results for treatment of cancer patients with hyperthermia are discussed, and it is concluded that treatment protocols probably should not prescribe more than one hyperthermic treatment per week.