Treatment of far-advanced bronchogenic carcinoma by extracorporeally induced systemic hyperthermia.

Hyperthermia (41.5° to 42.0° C) was induced in patients with preterminal bronchogenic carcinoma by use of a Dacron femoral arteriovenous shunt and a TDMAC-treated extracorporeal circuit (ECC) incorporating a heat exchanger. A temperature-regulating device (TRD) autoregulated the temperature of the heat exchanger and thereby of the patient to within ±0.1° C, as measured in the urinary bladder with a thermistor-tipped Foley catheter. A total of 97 treatments averaging 5 hours in duration were administered to 25 patients, 23 of whom previously had had unsuccessful radiation/chemotherapy. Cyclophosphamide (250 mg/m2) and BCNU (50 mg) were given during mid-hyperthermia. The distribution of tumor cell type was squamous cell in 15 (60%), large cell in four (16%), adenocarcinoma in three (12%), oat cell in two (8%), and alveolar cell carcinoma in one (4%). Adverse effects were principally moderate marrow suppression. Neurologic abnormalities occurred early in the series but were eliminated by maintenance of serum phosphate levels. Eighteen patients (72%) have died, 11 of tumor progression (of whom six completed hyperthermic treatment), four of infection or bleeding of necrosing tumor, and three of treatment complications. Patients who had had a pneumonectomy or who had significant chronic obstructive pulmonary disease adequately tolerated treatment. There was no instance of ECC-related hemolysis, thromboembolism, or significant cardiac failure. Antitumor effects were evidenced by roentgenographic, physical, or histologic findings in 16 of 25 patients (64%). Regressions were typically incomplete, and progression occurred 4 to 6 months after hyperthermia in seven of the 12 patients (58%) at risk. Four patients have stable regressed disease 7, 8, 13, and 20 months after hyperthermia. These data suggest the following: (1) Hyperthermia can cause regression of bronchogenic carcinoma resistant to other modes of therapy; (2) hyperthermia of 5 hours’ duration and 41.5° to 42.0° C magnitude will not routinely control bronchogenic carcinoma even with adjuvant cytotoxic agents; (3) further exploration of treatment regimens, particularly as applied to minimal residual disease, may be indicated.