Cancer occurring in the liver, even though confined to the liver, is usually incurable. Hyperthermia (41-43 degrees C) can cause regression of cancer in animals and in man. Perhaps the acquisition of thermosensitivity occurs with transformation of normal tissue to neoplastic tissue. The effects of hyperthermia and of chemotherapy enhance one another. Thermochemotherapy, delivered by isolation and perfusion of the liver, should be worthy of clinical trial. The goal of the proposed research plan is to demonstrate the safety and efficacy of thermochemotherapy delivered by isolation-perfusion of the liver for the treatment of liver cancer. The followng studies will be conducted: 1) the thermal threshold for reversible effects of hyperthermia on the isolated perfused rat liver will be determined by measuring these functions - oxygen consumption, gluconeogenesis, urea, protein, and nucleic acid ssnthesis; 2) the effects of several individual antineoplastic drugs (actinomycin-D, Adriamycin, BCNU, DTIC, bleomycin, and cis-platinum) combined with hyperthermia on the above liver functions will be studied; 3) the effects of hyperthermia alone and combined with the individual tumor agents above will be evaluated in the isolated perfused regenerating rat liver and in livers bearing the intrahepatic transplanted tumor, the Novikoff hepatoma; 4) the deffects of hyperthermia alone and combined wit the antineoplastic agents listed above on the 3-methy-4-N-dimethylaminoazobenzene-induced tumor-bearing rat liver functions will be studied; 5) the technique of isolation-perfusion of the liver of a large mammal (the dog) will be perfected, and the limits of tolerance of the whole animal to isolated liver perfusion will be determined; and, 6) a phase I study of hyperthermic isolation-perfusion of the liver in patients with hepatic metastases from large bowel cancer will be performed.