Therapeutic hyperthermia: contribution from clinical studies in dogs with spontaneous neoplasia

Dogs with spontaneously arising tumors have contributed greatly to the field of therapeutic hyperthermia. Pharmacologic, physiologic and immunologic characterization of the response to hyperthermia combined with radiation and chemotherapy in dogs has helped in development of new heating methods, warned of significant toxicity prior to human testing, and defined the effect of heat on drug distribution and relative potency. Clinical trials have been conducted in dogs with spontaneously arising cancer to refine treatment protocols prior to human clinical testing and have demonstrated the tumor control advantage of combined radiation/hyperthermia compared to radiation only in numerous prospective, phase III trials. These studies can be conducted less expensively and more rapidly than comparable studies in humans. This paradigm demonstrates the value of an intermediate, clinically relevant model in the study of novel treatment strategies and should continue to be used to investigate important issues for the benefit of both humans and animals with cancer.