Tc. Hardin et al., NUTRITIONAL PARAMETERS OBSERVED DURING 28-DAY INFUSION OF RECOMBINANTHUMAN TUMOR-NECROSIS-FACTOR-ALPHA, JPEN. Journal of parenteral and enteral nutrition, 17(6), 1993, pp. 541-545
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.