PULMONARY TOXICITY OF ALPHA-TUMOR-NECROSIS-FACTOR IN PATIENTS TREATEDBY ISOLATION PERFUSION

We studied pulmonary function in 22 patients affected by in-transit me tastases from cutaneous melanoma and metastases from soft tissue sarco ma of the limbs who were treated with isolation perfusion in extracorp oreal circulation with rTNF alpha at doses ranging from 0.5 to 4 mg/m( 2) in mild hyperthermia. Seventeen patients suffered from respiratory insufficiency which required assisted ventilation (7 mechanical ventil ation for 1 day, 8 for 2 days and 2 patients on synchronized intermitt ent. mandatory ventilation). Spirometric parameters recorded 7 to 15 d ays after treatment did not change from baseline values; in contrast, lung transfer factor for carbon monoxide significantly declined in a d ose dependent fashion. These data confirm that rTNF alpha administered by isolation perfusion technique induces pulmonary side effects. Furt her studies are required to better define time course and reversibilit y of impairment in pulmonary function.