Preliminary results of a phase III trial of spontaneous animal tumors to heat and/or radiation: early normal tissue response and tumor volume influence on initial response.

A Phase III randomized trial was initiated to test the relative efficacies of heat alone, radiation alone and heat plus radiation using spontaneous malignancies in pet animals. Heat alone was inferior to the other two treatment arms as demonstrated by a significantly higher non-response rate and shorter response duration. The ratio of complete response rates (CR) for heat plus radiation to radiation alone or the thermal relative risk (TRR) was greater for tumors greater than 10 cm3 as compared to those less than 10 cm3 (TRR = 4.8 and 1.4, respectively). The overall TRR for complete responses was 2.3. The CR data for the combined therapy arm indicate at least an additive effect between heat and radiation for small tumors but most likely a synergistic effect in the larger tumor group. Based on the data currently available, no significant difference in response duration is observed between the two radiation arms, although a nonsignificant advantage to the combination therapy exists. Normal tissue effects were evaluated by incidence of full moist desquamation within the irradiated volume, late fibrosis and bone necrosis. Since the radiation skin dose depended upon the technique being used it was possible to estimate the dose to achieve moist desquamation in 50% of the animals (DD50) by a logistic regression model as being 3728 +/- 344 rad for radiation alone. Significant lowering of the DD50 was not observed for the addition of heat to radiation. Low patient numbers where intact skin was heated prevented an accurate analysis of the effect, however.