Hardin T C, Koeller J M, Kuhn J G, Roodman G D, Von Hoff D D
Department of Pharmacology, University of Texas Health Science Center at San Antonio.
JPEN J Parenter Enteral Nutr. 1993 Nov-Dec;17(6):541-5. doi: 10.1177/0148607193017006541.
In conjunction with a Phase I investigation of the antineoplastic activity of recombinant human tumor necrosis factor-alpha (TNF-alpha), administered as a 28-day continuous infusion, selected nutritional parameters 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 significant malnutrition before entry into the study. Five patients received 10 micrograms of recombinant human TNF-alpha per square meter per day and two patients received 25 micrograms/m2 per day. Indirect calorimetry assessment of resting energy expenditure, body weight, serum TNF concentration, and laboratory analysis of common nutritional markers (albumin, prealbumin, and triglycerides) were performed at baseline, day 14, day 28, and 2 weeks (day 42) after completion of the infusion. There were no statistically 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 parameters when stratified by dose administered, although the number of patients studied was small. Measured serum TNF concentrations ranged from 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 concentrations and resting energy expenditure. Although others have reported significant metabolic changes associated with acute administration of TNF in humans and animals, our experience does not support a hypermetabolic state in patients receiving low daily dose, long-term (28-day) continuous infusion of recombinant human TNF-alpha, a state that may be consistent with many neoplastic conditions.
在一项关于重组人肿瘤坏死因子-α（TNF-α）抗肿瘤活性的Ⅰ期研究中，TNF-α以连续输注28天的方式给药，同时对选定的营养参数进行评估，以确定可能归因于TNF输注的任何影响。研究了7名患有多种肿瘤类型且临床状况稳定的男性。在进入研究之前，没有人有明显营养不良的临床或实验室证据。5名患者每天每平方米接受10微克重组人TNF-α，2名患者每天接受25微克/平方米。在基线、第14天、第28天以及输注完成后2周（第42天）进行静息能量消耗的间接量热法评估、体重测量、血清TNF浓度检测以及常见营养指标（白蛋白、前白蛋白和甘油三酯）的实验室分析。与基线值和第42天的值相比，在研究期间通过方差分析观察到任何参数均无统计学显著差异。此外，按给药剂量分层时，任何参数之间也没有差异，尽管研究的患者数量较少。测得的血清TNF浓度范围为0.02至1.56 ng/mL，与研究天数或输注的TNF剂量无关。血清TNF浓度与静息能量消耗之间未观察到相关性。尽管其他人报告了在人和动物中急性给予TNF会导致显著的代谢变化，但我们的经验并不支持接受低日剂量、长期（28天）连续输注重组人TNF-α的患者出现高代谢状态，而这种状态可能与许多肿瘤疾病相符。
