Background. Animal models suggest that cyclooxygenase-2 (COX-2) inhibitors may be beneficial in suppressing cancer cachexia. We investigated the effect of short-course celecoxib on body composition, inflammation, and quality of life (QOL) in patients with cancer cachexia in a phase II clinical pilot trial.Methods. Eleven cachectic patients with head and neck or gastrointestinal cancer were randomly assigned to receive placebo or celecoxib for 21 days while awaiting the initiation of cancer therapy. Body composition, resting energy expenditure, QOL, physical function, and inflammatory markers were measured on days 1 and 21.Results. Patients receiving celecoxib experienced statistically significant increases in weight and body mass index (BMI), while patients receiving placebo experienced weight loss and a decline in BMI. Patients receiving celecoxib also had increases in QOL scores.Conclusions. This syndrome is distinct from starvation in that it involves preferential wasting of lean body mass (LBM) while visceral proteins are preserved; elevated systemic inflammation, including increased levels of acute phase proteins and inflammatory cytokines; and elaboration of tumor-derived catabolic factors.2 Cachexia remains difficult to treat, with few U.S. Food and Drug Administrationapproved therapeutic options other than megestrol acetate, dronabinol, and oxandrolone.2 These

Cancer cachexia is a morbid wasting syndrome common among patients with head and neck cancer. While its clinical manifestations have been well characterized, its pathophysiology remains complex. A comprehensive literature search on cancer cachexia was performed using the National Library of Medicine's PubMed. The Cochrane Library and Google search engine were also used. Recent evidence and new concepts on the pathophysiology of cancer cachexia are summarized. Targeted therapies are presented, and new concepts are highlighted. Cancer cachexia is characterized by complex, multilevel pathogenesis. It involves up-regulated tissue catabolism and impaired anabolism, release of tumor-derived catabolic factors and inflammatory cytokines, and neuroendocrine dysfunction. These culminate to create an energy-inefficient state characterized by wasting, chronic inflammation, neuroendocrine dysfunction, and anorexia.

BackgroundNonsteroidal anti-inflammatory drugs (NSAIDs) may palliate cachexia by maintaining muscle mass. A recent animal study demonstrated that cyclooxygenase 2 inhibitors (COX-2) reversed tumor-induced wasting in mice bearing human head and neck squamous cell carcinoma and colon carcinomas. Our hypothesis was that NSAIDs given to patients with cancer cachexia will stabilize or reverse their loss of lean body mass.MethodsA prospective, randomized, double-blind, placebo-controlled clinical trial was designed to determine whether intervention with the COX-2 inhibitor celecoxib was effective at improving cancer cachexia in patients with cancer of the head and neck and gastrointestinal (GI) tract. After the clinical diagnosis of cachexia was established, the following measurements were made: weight; body composition via dual x-ray absorptiometry; resting energy expenditure (REE) via indirect calorimetry; quality of life (QoL) surveys via Functional Assessment of Anorexia/Cachexia Therapy (FAACT); and performance status via Karnofsky Performance Scale (KPS). Patients were randomized to receive either celecoxib 200 mg po bid or placebo for 3 weeks. Three weeks later, each patient returned for the same evaluation as on day 1. In this pilot study, no nutritional intervention was made.ResultsEleven patients have completed the study thus far. Seven have received placebo, while four have received active drug. Eight patients have head and neck cancers and three patients have cancer of the GI tract. All were male, with a mean age of 59.1 years. Interim unblinded analysis of the data reveals that, on average, patients taking celecoxib experienced weight gain of 1.0 kg (SE = 1.33), body mass index (BMI) increase of 0.31 (SE = 0.45), lean body mass percent (LBM%) increase of 0.28 (SE = 2.81), and improvement of FAACT score of 10 points (SE = 4). Those taking placebo experienced, on average, weight loss of 1.0 kg (SE = 1.63), BMI decrease of 0.56 (0.68), LBM% drop of 0.04% (SE = 1.60), and no improvement in FAACT score.ConclusionsPromising initial trends were seen in the administration of celecoxib to patients with cancer cachexia in this study, including gains in weight, BMI, LBM%, and QoL score. Future studies may examine cytokine and CRP levels and may include a nutritional intervention in studying the effect of anti-inflammatory therapy on cancer cachexia.