Thermochemotherapy (combined cyclophosphamide and hyperthermia) with or without hyperglycemia as an adjuvant to...

Our previous study demonstrated the presence of a thermochemotherapy-resistant cell fraction in a tumor. The present study investigated whether thermochemotherapy-resistant cells are radioresistant and whether thermochemotherapy changes the size of hypoxic cell fraction in the tumor. Early generation isotransplants of a spontaneous fibrosarcoma, FSa-II tumors, were used. A radiation dose that yields 50% tumor control rate in 150 days after local irradiation, TCD50, was determined. Cyclophosphamide (CY) was the test agent. TCD50 values of the 4 mm tumor following gamma-ray alone given under hypoxic conditions or in air were 80.9 or 65.8 Gy, respectively. Thermochemotherapy reduced TCD50 values congruent to 20 Gy, suggesting that thermochemotherapy resistant cells are not identical to the radioresistant cells. Glucose administered 60 min before thermochemotherapy further reduced TCD50 values. Foot-reaction scored in the tumor-controlled animals was significantly less severe following combined thermochemo- and radiotherapy compared to that following radiotherapy alone. Acute foot reaction studies also supported this observation. These results indicated that thermochemotherapy could be an excellent adjuvant to radiotherapy. Further studies using a 6 mm tumor indicated that thermochemotherapy was less effective on the large tumor than on the small tumor. Indirect analysis showed no significant changes in the size of hypoxic cell fraction following thermochemotherapy.