Abstract
BACKGROUND.
Tumor necrosis factor‐α (TNF‐α) is a putative mediator of the cancer anorexia/weight loss syndrome. The current study was designed to determine whether etanercept (a dimeric fusion protein consisting of the extracellular ligand‐binding portion of the human 75‐kilodalton TNF receptor linked to the Fc portion of human immunoglobulin [Ig] G1) could palliate this syndrome.
METHODS.
A total of 63 evaluable patients were randomly assigned to receive either etanercept at a dose of 25 mg subcutaneously twice weekly versus a comparably administered placebo. All patients had an incurable malignancy, acknowledged loss of weight and/or appetite as a concern, and reported a weight loss of >2.27 kg over 2 months and/or a daily intake of <20 calories/kg body weight.
RESULTS.
Over time, weight gain was found to be minimal in both treatment arms; no patient gained ≥10% of their baseline weight. Previously validated appetite questionnaires revealed negligible improvements in both treatment arms. The median survival was also comparable (175 days vs 148 days in etanercept‐treated and placebo‐exposed patients, respectively; P = .82). Finally, preliminary data regarding adverse events demonstrated that patients treated with etanercept had higher rates of neurotoxicity (29% vs 0%) but lower rates of anemia (0% vs 19%) and thrombocytopenia (0% vs 14%). Infection rates were negligible in both groups. Genotyping for TNF‐α‐238 and TNF‐α‐308 polymorphisms revealed no clinical significance for these genotypes, except for a preliminary association between presence of the −238 G/A genotype and relatively less favorable survival.
CONCLUSIONS.
Etanercept, as prescribed in the current trial, does not appear to palliate the cancer anorexia/weight loss syndrome in patients with advanced disease. Cancer 2007. © 2007 American Cancer Society.