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.
BACKGROUND
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.


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 >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.


CONCLUSIONS
Etanercept, as prescribed in the current trial, does not appear to palliate the cancer anorexia/weight loss syndrome in patients with advanced disease.
Department of Oncology, Mayo Clinic, Rochester, Minnesota 55905, USA. jatoi.aminah@mayo.edu
Aminah
A
Jatoi
Shaker R
SR
Dakhil
Phuong L
PL
Nguyen
Jeff A
JA
Sloan
John W
JW
Kugler
Kendrith M
KM
Rowland
Gamini S
GS
Soori
Donald B
DB
Wender
Tom R
TR
Fitch
Paul J
PJ
Novotny
Charles L
CL
Loprinzi
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000855:Anorexia / Q000139:chemically induced / Q000188:drug therapy* / Q000209:etiology*; D000970:Antineoplastic Agents / Q000009:adverse effects; D001066:Appetite / Q000187:drug effects*; D004311:Double-Blind Method; D000068800:Etanercept; D005260:Female; D005838:Genotype; D006801:Humans; D007074:Immunoglobulin G / Q000009:adverse effects / Q000627:therapeutic use*; D007155:Immunologic Factors / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000150:complications* / Q000188:drug therapy / Q000628:therapy*; D010166:Palliative Care / Q000379:methods; D011788:Quality of Life; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use*; D011795:Surveys and Questionnaires; D016019:Survival Analysis; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D015430:Weight Gain / Q000187:drug effects*; D015431:Weight Loss / Q000187:drug effects
D000970:Antineoplastic Agents; D007074:Immunoglobulin G; D007155:Immunologic Factors; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D000068800:Etanercept