Effect of thermochemotherapy (combined cyclophosphamide and hyperthermia) given at various temperatures with or without glucose administration on a murine fibrosarcoma

The effect of combined cyclophosphamide (CY) and heat treatments on a murine tumor was studied at various temperatures. FSa-II tumors, the early generation isotransplants of a spontaneous fibrosarcoma in a C3Hf/Sed mouse, were used. A single cell suspension was transplanted into the animal foot. Hyperthermia was given by immersing animal feet into a water bath maintained at a desired temperature +/- 0.1 degrees C. An average diameter of the tumor at the time of treatment was 4 mm. The tumor growth time, the time required for one-half of the treated tumors to reach 1000 mm3, was the end point. Hyperthermia enhanced the effect of CY at test temperatures ranging from 40.5 degrees - 44.5 degrees C. The enhancement was independent of the temperature when CY was administered 30 min before the beginning of hyperthermia. However, the enhancement was most substantial at temperatures of 40.5 degrees -42.5 degrees C when CY was administered immediately before hyperthermia. The most effective timing of the CY administration was immediately before hyperthermia. The glucose administered 60 min before hyperthermia enhanced the effect of combined CY and hyperthermia when CY was given 30 min before heating. This enhancement was lost when CY was given immediately before hyperthermia. The CY dose response curves at elevated temperatures were downward concave, which may indicate the presence of a CY- and heat-resistant cell population in the tumor. Implications of these observations in clinical hyperthermia were discussed.