Caquexia

Support Care Cancer (2010) 18:1–9 DOI 10.1007/s00520-009-0722-3

REVIEW ARTICLE

Cancer cachexia: medical management
Giovanni Mantovani & Clelia Madeddu

Received: 6 April 2009 / Accepted: 3 August 2009 / Published online: 18 August 2009 # Springer-Verlag 2009

Abstract Background Cachexia is a complex metabolic syndrome associated with many chronic or end-stage diseases, especiallycancer, and is characterized by loss of muscle with or without loss of fat mass. The management of cachexia is a complex challenge that should address the different causes underlying this clinical event with an integrated or multimodal treatment approach targeting the different factors involved in its pathophysiology. Materials and methods The purpose of this article was to review the current medicaltreatment of cancer-related cachexia, in particular focusing on combination therapy and ongoing research. Results Among the treatments proposed in the literature for cancer-related cachexia, some proved to be ineffective, namely, cyproheptadine, hydrazine, metoclopramide, and pentoxifylline. Among effective treatments, progestagens are currently considered the best available treatment option forcancer-related cachexia, and they are the only drugs approved in Europe. Drugs with a strong rationale that have failed or have not shown univocal results in clinical trials so far include eicosapentaenoic acid, cannabinoids, bortezomib, and anti-TNF-alpha MoAb. Several emerging drugs have shown promising results but are still under clinical investigation (thalidomide, selective cox-2 inhibitors,ghrelin mimetics, insulin, oxandrolone, and olanzapine). Conclusions To date, despite several years of co-ordinated efforts in basic and clinical research, practice guidelines for the prevention and treatment of cancer-related muscle

wasting are lacking, mainly because of the multifactorial pathogenesis of the syndrome. From all the data presented, one can speculate that one single therapy maynot be completely successful in the treatment of cachexia. From this point of view, treatments involving different combinations are more likely to be successful. Keywords Cancer cachexia . Medical management . Progestagens . Combined approach

Definition of cachexia Cachexia is a complex metabolic syndrome associated with underlying illness and characterized by loss of muscle with or without lossof fat mass. Cachexia can occur as part of many chronic or end-stage diseases such as infections, cancer, AIDS, congestive heart failure, chronic renal failure, rheumatoid arthritis, tuberculosis, and chronic obstructive pulmonary disease. The prominent clinical feature of cachexia is weight loss in adults (corrected for fluid retention). Anorexia, inflammation, insulin resistance, and increasedmuscle protein breakdown are frequently associated with cachexia. Cachexia is distinct from starvation, age-related loss of muscle mass, primary depression, malabsorption, and hyperthyroidism and is associated with increased morbidity [1]. Cachexia defines a distinct clinical syndrome where the activation of proinflammatory cytokines has a direct effect on muscle metabolism and anorexia [2].Multiple mechanisms appear to be involved in the development of cachexia, including anorexia, decreased physical activity, decreased secretion of host anabolic hormones, and altered host metabolic response with abnormalities in protein, lipid, and carbohydrate metabolism.

G. Mantovani (*) : C. Madeddu Department of Medical Oncology, University of Cagliari, Cagliari, Italy e-mail:mantovan@medicina.unica.it

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Support Care Cancer (2010) 18:1–9

Basically, cachexia is dependent from cytokine-driven dysregulation of the peripheral signals (mainly leptin, ghrelin, and serotonin), reaching the brain hypothalamic region, which plays a central role in balancing the orexigenic and anorexigenic signals, leading to decreased food intake and increased resting energy expenditure (REE). Indeed,...