A placebo-controlled double blind trial of etanercept for the cancer anorexia/weight loss syndrome: results from N00C1 from the North Central Cancer Treatment Group.

Tumor necrosis factor-alpha (TNF-alpha) 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. 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. Over time, weight gain was found to be minimal in both treatment arms; no patient gained >or=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-alpha-238 and TNF-alpha-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. Etanercept, as prescribed in the current trial, does not appear to palliate the cancer anorexia/weight loss syndrome in patients with advanced disease.