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Pharmacological treatment of the cachexia-anorexia-cancer syndrome

Abstract:

Cachexia-anorexia-cáncer syndrome (CAC Sy) is characterized by a high caloric demand, expression of endogenous anorexigenic substances, hormonal changes and alterations of carbohydrate, lipid and protein metabolism. These patients show anorexia, weight loss, inflammation and reduction of physical activity. CAC Sy is associated to hypoproteinemia, hypoalbuminemia, hypertriglyceridemia, anemia, glucose intolerance, insulin resistance and lactic acidosis. Pharmacological treatment of CAC Sy include progestagens (megestrol), psychostimulant agents, esteroids, anabolyzing compounds, antidepressants, anticholinergics, amphetamines, antiparkinsonian drugs and COX2 inhibitors. Analgesic and antinflammatory COX2 inhibitors are currently under investigation in the CAC Sy, because prostaglandins are involved in the development of the cachexia - anorexia process. Several studies have demonstrated in experimental animals that COX2 inhibitors have anticancer effects in models of colonic, vesical, skin and breast malignant tumors. Celecoxib (200 mg/bid/6 weeks) a selective COX2 inhibitor, administered to cancer patients, improves apetite, fatigue symptoms, C reactive protein and muscle strength, compared to placebo. Megestrol is regularly used in cachexia treatment because of its orexigenic effect in patients with advanced cancer; this progestagen reduce nausea and vomits, improving patient's quality of life; mediated through decreased synthesis of proinflammatory cytokines. On the other hand, the mechanism of anticancer effect of COX2 inhibitors include: 1) reduction of PG synthesis 2) preventions of free-radicals generation 3) interference with metabolic signals of carcinogenic compounds 4) reduction of cell replication 5) apoptosis induction 6) immune system stimulation, and 7) antiangiogenic effects.