Isolated lung perfusion with tumor necrosis factor for pulmonary metastases.
BACKGROUND
A phase I trial was initiated to define the feasibility and safety of single-lung isolation perfusion with tumor necrosis factor-alpha, interferon-gamma, and moderate hyperthermia for patients with unresectable pulmonary metastases.


METHODS
Twenty patients with lung metastases (Ewing's, 2; sarcoma, 8; melanoma, 6; other, 4) were considered for single-lung isolation perfusion with 0.3 to 6.0 mg of tumor necrosis factor-alpha and 0.2 mg interferon-gamma delivered through an oxygenated pump circuit. Sixteen perfusions were performed in 15 patients (bilateral in 1). Metastases were completely resected (no single-lung isolation perfusion) in 3 patients, 1 patient had extrapulmonary disease, and one single-lung isolation perfusion was aborted for mechanical reasons.


RESULTS
There were no significant changes in systemic arterial blood pressure or cardiac output during perfusion. Systolic pulmonary artery pressure increased with isolation, but returned to pre-single-lung isolation perfusion levels after clamp release. The maximum systemic tumor necrosis factor-alpha level was 8 ng/mL, whereas pump-circuit levels ranged from 200 to 10,976 ng/mL. There were no deaths, and the mean hospitalization period was 9 days (range, 5 to 34 days). A short-term (6 to 9 month) unilateral decrease in perfused nodules was noted in 3 patients (melanoma in 1, adenoid cystic carcinoma in 1, renal cell carcinoma in 1).


CONCLUSIONS
Future studies using a combination of biologic modifiers, chemotherapy, and hyperthermia should be pursued to define active cytotoxic agents that will preserve underlying pulmonary function.
Pass
H I
HI
Thoracic Oncology Section, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Mew
D J
DJ
Kranda
K C
KC
Temeck
B K
BK
Donington
J S
JS
Rosenberg
S A
SA
D000328:Adult; D001794:Blood Pressure; D003528:Carcinoma, Adenoid Cystic / Q000556:secondary / Q000628:therapy; D002292:Carcinoma, Renal Cell / Q000556:secondary / Q000628:therapy; D002302:Cardiac Output; D010478:Chemotherapy, Cancer, Regional Perfusion; D005240:Feasibility Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006979:Hyperthermia, Induced; D007371:Interferon-gamma / Q000627:therapeutic use; D008175:Lung Neoplasms / Q000556:secondary* / Q000601:surgery / Q000628:therapy*; D008297:Male; D008545:Melanoma / Q000556:secondary / Q000601:surgery / Q000628:therapy; D008875:Middle Aged; D010106:Oxygenators; D011651:Pulmonary Artery; D012074:Remission Induction; D012449:Safety; D012509:Sarcoma / Q000556:secondary / Q000601:surgery / Q000628:therapy; D012512:Sarcoma, Ewing / Q000556:secondary / Q000601:surgery / Q000628:therapy; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage / Q000032:analysis / Q000627:therapeutic use*
D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma