The general objective of this study is to establish an optimum multimodality treatment regimen using heat and chemotherapy that provides both maximum tumor ablation and minimal damage to critical dose limiting normal tissues. The response of a rat fibrosarcoma artificially metastatic to the lung will be used as a tumor model. These data will then be compared to the acute and chronic respones of those normal tissues considered dose limiting for the particular drug being tested. To determine the dose relationships of cisplatin, adriamycin, and bleomycin when given simultaneously with systemic hyperthermia on tumor response and to quantify the acute and late responses of the target normal tissues for each drug when combined with heat and with heat alone. To compare the pharmacokinetics of the chemotherapy agents at normal hyperthermic temperatures using serial tissue and serum drug analysis. To determine the effect of increasing the time interval between heat and drugs when given before and after heating on both the tumor response and the target normal tissue response. To determine if a biological response modifier, venoruton, a bioflavenoid oxyden free radical scavenging agent, preferentially spares the target normal tissue after heat and drug treatment. In addition to providing insight into the pharmacokinetics of drugs when combined with heat, and a knowledge of the effects of the combined therapies on normal tissues; the data obtained from these studies have potential importance to the management of patients using drugs combined with either local-regional or systemic hyperthermia.
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