Total-body hyperthermia with and without chemotherapy for advanced human neoplasms

Thirteen previously treated patients with metastatic tumors were subjected to systemic hyperthermia, alone or in combination with chemotherapy (melphalan, 5 patients; VP16, one patient), during their third treatment session. Heating was performed under general anesthesia by using water blankets at a water temperature of 49°. The treatment temperature of 41.9° to 42.0° was achieved within 1.5 to 3.5 hr and was maintained for 4 hr. Altogether 32 treatment sessions were associated with sinus tachycardia, a reduction in diastolic blood pressure, skin burns, and temperature elevation to >38° persisting for 24 to 36 hr after treatment. Mild to moderate diarrhea and nausea and/or vomiting were noted in one-half of all treatments. General weakness and fatigue prevented full ambulation in two-thirds of patients for 48 hr following treatment. Four patients with extensive prior Vinca alkaloid exposure developed peripheral neuropathy, one with additional severe rhabdomyolysis. Laboratory abnormalities included signs of low-grade disseminated intravascular coagulation with thrombocytopenia 24 hr after treatment, appearance of fibrin-split products, and occasional prolongation in prothrombin and partial thromboplastin time. Moderate hyperglycemia and mild degrees of hypocalcemia, hypomagnesemia, hypophosphatemia, and hypokalemia occurred acutely during therapy. Marked creatinine phosphokinase elevation was noted particularly after the first heat treatment. Electroencephalograms were recorded in 4 patients during 10 treatment sessions, revealing a marked slowing with temperature elevation beyond 40° and seizure activity in 2 patients. Convulsions were manifest in 2 patients without central nervous system metastases. Of 11 patients evaluable for antitumor effect, 7 achieved stable disease status. Four of these patients had objective signs of tumor regression (melanoma, 3 patients; lymphoma, one patient), all of which occurred after hyperthermia alone. Total-body hyperthermia at 42° for 4 hr is tolerated with acceptable toxicity by selected patients.