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Anorexia and Cachexia

  • Takao Ohnuma*
  • James F. Holland
Chapter
Part of the Cancer Drug Discovery and Development book series (CDD&D)

Abstract

Cachexia is a complex syndrome presenting wasting of muscle and adipose tissues, weight loss, anorexia, early satiety, fatigue, anemia, hyperlipidemia, systemic inflammatory responses, and often a hypercatabolic state. Cachexia differs from starvation, where visceral proteins are also depleted. Profound anorexia and early satiety are partly responsible, but metabolic abnormalities are the major cause of cachexia. Mechanisms of cachexia include production of inflammatory cytokines including TNF-α, Interleuken-1 (IL-1), IL-6, and IFN-γ; secretion of tumor byproducts, which include lipolytic factors and proteolysis-inducing factor; hormonal aberration; prostaglandin elevation; possible dysfunction of neuropeptidergic circuits; and metabolic derangement produced by treatment. A variety of agents have been used in attempts to reverse cachexia, including corticosteroids, megestrol acetate and medroxyprogesterone acetate, anabolic steroids, cannabinoids, growth hormones, somatostatin and GHRP-2, insulin-like growth factor 1, metoclopramide and cisapride, hydrazine sulfate, anti-inflammatory agents such as indomethacin and ibuprofen, pentoxifylline and lisofylline, proteasome inhibitors and NF-κB inhibitors, clenbuterol, thalidomide, adenosine triphosphate, 5′-deoxy-5-fluorouridine, proinflammatory-cytokine inhibitors including proinflammatory cytokine antibodies and anti-inflammatory cytokines, eicosapentaenoic acid, enteral and parenteral nutrition, branched-chain amino acids, orexigenic mediators, melatonin and cyproheptadine. Currently, the most commonly used agent is megestrol acetate; however, megestrol-induced weight gain is mainly from water and fat, rather than muscle protein. Side effects include thromboembolic phenomena. In early studies, thalidomide and NF-κB inhibitors appear effective at attenuating loss of weight and lean body mass in cancer cachexia. Development of agents that prevent or reverse loss of lean body weight mass is eagerly awaited.

Key Words:

Anorexia Cachexia Mechanisms Serotonin Inflammatory cytokines Lipid-mobilizing factor Prostaglandin Proteolysis-inducing factor Corticosteroids Megestrol acetate NF-κB inhibitors Thalidomide Eicosapentaenoic acid 

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Copyright information

© Humana Press, a part of Springer Science + Business Media, LLC 2009

Authors and Affiliations

  • Takao Ohnuma*
    • 1
  • James F. Holland
    • 1
  1. 1.Division of Hematology/OncologyDepartment of Medicine, Mount Sinai School of MedicineUSA

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