NUTRITIONAL PARAMETERS OBSERVED DURING 28-DAY INFUSION OF RECOMBINANTHUMAN TUMOR-NECROSIS-FACTOR-ALPHA

In conjunction with a Phase I investigation of the antineoplastic acti vity of recombinant human tumor necrosis factor-alpha (TNF-alpha), adm inistered as a 28-day continuous infusion, selected nutritional parame ters were evaluated to identify any effect that might be attributed to the TNF infusion. Seven clinically stable men with a variety of tumor types were studied. None had clinical or laboratory evidence of signi ficant malnutrition before entry into the study. Five patients receive d 10 mug of recombinant human TNF-alpha per square meter per day and t wo patients received 25 mug/m2 per day. Indirect calorimetry assessmen t of resting energy expenditure, body weight, serum TNF concentration, and laboratory analysis of common nutritional markers (albumin, preal bumin, and triglycerides) were performed at baseline, day 14, day 28, and 2 weeks (day 42) after completion of the infusion. There were no s tatistically significant differences by analysis of variance observed in any parameter during the study period compared with baseline values and values on day 42. Also, there were no differences between any par ameters when stratified by dose administered, although the number of p atients studied was small. Measured serum TNF concentrations ranged fr om 0.02 to 1.56 ng/mL and did not correlate with study day or dose of TNF infused. No correlation was observed between serum TNF concentrati ons and resting energy expenditure. Although others have reported sign ificant metabolic changes associated with acute administration of TNF in humans and animals, our experience does not support a hypermetaboli c state in patients receiving low daily dose, long-term (28-day) conti nuous infusion of recombinant human TNF-alpha, a state that may be con sistent with many neoplastic conditions.