Cardiac and pulmonary effects of alpha tumor necrosis factor administered by isolation perfusion.
OBJECTIVE
We studied cardiac and pulmonary function in 22 patients affected by in transit metastases from cutaneous melanoma and metastases from soft tissue sarcoma of the limbs and treated with isolation perfusion in extracorporeal circulation with rTNF alpha at doses ranging from 0.5 to 4 mg/m2 in mild hyperthermia.


METHODS
All patients experienced a septic-like shock syndrome of variable severity: this feature lasted from 24 to 72 h and was controlled by the infusion of dopamine. Seventeen patients suffered from respiratory insufficiency, which required assisted ventilation (7 cases mechanical ventilation for 1 day, 8 cases for 2 days, and 2 cases synchronized intermittent mandatory ventilation).


RESULTS
Spirometric parameters recorded 7-15 days after treatment did not change from baseline values. In contrast, lung transfer factor for carbon monoxide significantly declined in a dose dependent fashion.


CONCLUSIONS
Our data confirm that rTNF alpha administered by isolation perfusion technique induces systemic cardiovascular and pulmonary side effects. Further studies are required to better define time course and reversibility of impaired pulmonary function.
Villani
F
F
Divisione di Cardiologia e Fisiopatologia Respiratoria, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milano, Italy.
Galimberti
M
M
Mazzola
G
G
Stifani
I
I
Santinami
M
M
Rizzi
M
M
Manzi
R
R
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001132:Arm; D010478:Chemotherapy, Cancer, Regional Perfusion; D004298:Dopamine / Q000627:therapeutic use; D005260:Female; D006321:Heart / Q000187:drug effects*; D006334:Heart Function Tests; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007866:Leg; D008168:Lung / Q000187:drug effects*; D008297:Male; D008545:Melanoma / Q000188:drug therapy / Q000503:physiopathology*; D008875:Middle Aged; D012129:Respiratory Function Tests; D012509:Sarcoma / Q000188:drug therapy / Q000503:physiopathology* / Q000556:secondary; D012772:Shock, Septic / Q000139:chemically induced* / Q000188:drug therapy; D012878:Skin Neoplasms / Q000188:drug therapy / Q000503:physiopathology*; D013577:Syndrome; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage / Q000494:pharmacology*
D000970:Antineoplastic Agents; D014409:Tumor Necrosis Factor-alpha; D004298:Dopamine