The influence of levamisole and hyperthermia on the incidence of metastases from an X-irradiated tumor.

Fragments of the KHT sarcoma were transplanted into the right rear legs of C3H/He mice. At 10 days, groups of 16 to 20 mice had the consequent developing tumor treated by local irradiation (40 Gy in 2 fractions), levamisole (5 mg/kg every 2nd day), local hyperthermia, or a combination of these treatments. Local tumor control, the incidence and sites of metastatic spread, and survival times were measured. Radiation alone controlled 25% of the local tumors, but 75% of the treated mice developed metastases. Radiation combined with levamisole increased local control to 31% with a corresponding decrease in the incidence of metastases. Hyperthermia alone prolonged the survival time compared to nontreated mice. This increase in survival time was lost when levamisole was combined with hyperthermia. Combined hyperthermia and irradiation controlled 89% of tumors. This corresponded to a thermal enhancement factor of 3.5. When levamisole was added to hyperthermia and irradiation, local tumor control was decreased and the incidence of metastases was increased compared to the combination treatment of irradiation and hyperthermia. The nonspecific immune stimulant levamisole was antagonistic to the action of hyperthermia on the KHT tumor. An hypothesis to explain this antagonism is proposed.