Official reprint from UpToDate®
www.uptodate.com ©2017 UpToDate, Inc. and/or its affiliates. All Rights Reserved.

Pathogenesis, clinical features, and assessment of cancer cachexia

Aminah Jatoi, MD
Charles L Loprinzi, MD
Section Editor
Paul J Hesketh, MD
Deputy Editor
Diane MF Savarese, MD


Hippocrates described a syndrome of wasting and progressive inanition among patients who were ill and dying. The Greek words kakos, meaning "bad things," and hexus, meaning "state of being," have led to the term cachexia to describe this syndrome. Cachexia, a hypercatabolic state defined as accelerated loss of skeletal muscle in the context of a chronic inflammatory response, can occur in the setting of advanced cancer as well as in chronic infection, acquired immunodeficiency syndrome (AIDS), heart failure, rheumatoid arthritis, and chronic obstructive pulmonary disease [1]. Although body composition changes are not identical in all of these disease states, the term cachexia is used in all of these settings. (See "Palliative care: Assessment and management of anorexia and cachexia", section on 'Prevalence and clinical significance' and "Palliative care: Assessment and management of anorexia and cachexia", section on 'Etiology and pathogenesis'.)

Loss of appetite with weight loss is common among cancer patients [2-4]. However, the profound weight loss suffered by patients with cachexia cannot be entirely attributed to poor caloric intake. Insufficient oral intake is superimposed upon complex metabolic aberrations that lead to an increase in basal energy expenditure and culminate in a loss of lean body mass from skeletal muscle wasting. In contrast to simple starvation, which is characterized by a caloric deficiency that can be reversed with appropriate feeding, the weight loss of cachexia cannot be adequately treated with aggressive feeding.

This topic will review the definitions, pathogenesis, and clinical characteristics of cancer cachexia. Potential pharmacologic therapies for cancer-related anorexia/cachexia syndrome and a separate discussion of assessment and management of anorexia/cachexia in palliative care patients are discussed separately. (See "Pharmacologic management of cancer anorexia/cachexia" and "Palliative care: Assessment and management of anorexia and cachexia".)


Historically, cancer cachexia has been most often defined by loss of weight (eg, involuntary weight loss >10 percent) [5]. However, the measurement of body weight may underestimate the frequency of cachexia in patients who are overweight/obese, or who have gained weight because of edema or a growing tumor mass [6,7]. As an example, largely because of the obesity epidemic in industrialized nations, cancer patients who historically were visibly cachectic with a body mass index (BMI) <20 may not be discernible as cachectic and in fact, have a normal or increased BMI [8,9].

More recently, clinicians and researchers interested in cachexia have gathered formally to consider the definition of cachexia and its underlying or component elements as well as diagnostic criteria. The evolution of the concept of cachexia is expanding to encompass specific elements of body composition, functional consequences, and biochemical signs of specific metabolic change:

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:

Subscribers log in here

Literature review current through: Sep 2017. | This topic last updated: Oct 02, 2017.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2017 UpToDate, Inc.
  1. Kotler DP. Cachexia. Ann Intern Med 2000; 133:622.
  2. Teunissen SC, Wesker W, Kruitwagen C, et al. Symptom prevalence in patients with incurable cancer: a systematic review. J Pain Symptom Manage 2007; 34:94.
  3. Oncology. Clin Privil White Pap 2000; :1.
  4. Tchekmedyian NS. Costs and benefits of nutrition support in cancer. Oncology (Williston Park) 1995; 9:79.
  5. Davis MP, Dickerson D. Cachexia and anorexia: cancer's covert killer. Support Care Cancer 2000; 8:180.
  6. Fearon K, Strasser F, Anker SD, et al. Definition and classification of cancer cachexia: an international consensus. Lancet Oncol 2011; 12:489.
  7. Blum D, Strasser F. Cachexia assessment tools. Curr Opin Support Palliat Care 2011; 5:350.
  8. Sarhill N, Mahmoud F, Walsh D, et al. Evaluation of nutritional status in advanced metastatic cancer. Support Care Cancer 2003; 11:652.
  9. Del Fabbro E, Hui D, Dalal S, et al. Clinical outcomes and contributors to weight loss in a cancer cachexia clinic. J Palliat Med 2011; 14:1004.
  10. Evans WJ, Morley JE, Argilés J, et al. Cachexia: a new definition. Clin Nutr 2008; 27:793.
  11. Strasser F. Diagnostic criteria of cachexia and their assessment: decreased muscle strength and fatigue. Curr Opin Clin Nutr Metab Care 2008; 11:417.
  12. EPCRC Clinical Practice Guidelines on cancer cachexia available online at http://www.epcrc.org/publication_listfiles.php?id=mWdBCMI5eXVlcNFk7Gnq (Accessed on July 15, 2013).
  13. Baumgartner RN, Koehler KM, Gallagher D, et al. Epidemiology of sarcopenia among the elderly in New Mexico. Am J Epidemiol 1998; 147:755.
  14. Kim TN, Yang SJ, Yoo HJ, et al. Prevalence of sarcopenia and sarcopenic obesity in Korean adults: the Korean sarcopenic obesity study. Int J Obes (Lond) 2009; 33:885.
  15. Rolland Y, Lauwers-Cances V, Cristini C, et al. Difficulties with physical function associated with obesity, sarcopenia, and sarcopenic-obesity in community-dwelling elderly women: the EPIDOS (EPIDemiologie de l'OSteoporose) Study. Am J Clin Nutr 2009; 89:1895.
  16. Prado CM, Lieffers JR, McCargar LJ, et al. Prevalence and clinical implications of sarcopenic obesity in patients with solid tumours of the respiratory and gastrointestinal tracts: a population-based study. Lancet Oncol 2008; 9:629.
  17. Tisdale MJ. Cachexia in cancer patients. Nat Rev Cancer 2002; 2:862.
  18. Fredrix EW, Wouters EF, Soeters PB, et al. Resting energy expenditure in patients with non-small cell lung cancer. Cancer 1991; 68:1616.
  19. Staal-van den Brekel AJ, Schols AM, ten Velde GP, et al. Analysis of the energy balance in lung cancer patients. Cancer Res 1994; 54:6430.
  20. Stallings VA, Vaisman N, Chan HS, et al. Energy metabolism in children with newly diagnosed acute lymphoblastic leukemia. Pediatr Res 1989; 26:154.
  21. Peacock JL, Inculet RI, Corsey R, et al. Resting energy expenditure and body cell mass alterations in noncachectic patients with sarcomas. Surgery 1987; 102:465.
  22. Leibel RL, Rosenbaum M, Hirsch J. Changes in energy expenditure resulting from altered body weight. N Engl J Med 1995; 332:621.
  23. Dempsey DT, Feurer ID, Knox LS, et al. Energy expenditure in malnourished gastrointestinal cancer patients. Cancer 1984; 53:1265.
  24. Dempsey DT, Knox LS, Mullen JL, et al. Energy expenditure in malnourished patients with colorectal cancer. Arch Surg 1986; 121:789.
  25. Tocco-Bradley R, Georgieff M, Jones CT, et al. Changes in energy expenditure and fat metabolism in rats infused with interleukin-1. Eur J Clin Invest 1987; 17:504.
  26. Van der Poll T, Romijn JA, Endert E, et al. Tumor necrosis factor mimics the metabolic response to acute infection in healthy humans. Am J Physiol 1991; 261:E457.
  27. Hellerstein MK, Meydani SN, Meydani M, et al. Interleukin-1-induced anorexia in the rat. Influence of prostaglandins. J Clin Invest 1989; 84:228.
  28. Sonti G, Ilyin SE, Plata-Salamán CR. Anorexia induced by cytokine interactions at pathophysiological concentrations. Am J Physiol 1996; 270:R1394.
  29. Davis MP, Dreicer R, Walsh D, et al. Appetite and cancer-associated anorexia: a review. J Clin Oncol 2004; 22:1510.
  30. Walsh D, Mahmoud F, Barna B. Assessment of nutritional status and prognosis in advanced cancer: interleukin-6, C-reactive protein, and the prognostic and inflammatory nutritional index. Support Care Cancer 2003; 11:60.
  31. Zeisler H, Tempfer C, Joura EA, et al. Serum interleukin 1 in ovarian cancer patients. Eur J Cancer 1998; 34:931.
  32. Mantovani G, Macciò A, Mura L, et al. Serum levels of leptin and proinflammatory cytokines in patients with advanced-stage cancer at different sites. J Mol Med (Berl) 2000; 78:554.
  33. Staal-van den Brekel AJ, Dentener MA, Schols AM, et al. Increased resting energy expenditure and weight loss are related to a systemic inflammatory response in lung cancer patients. J Clin Oncol 1995; 13:2600.
  34. Falconer JS, Fearon KC, Plester CE, et al. Cytokines, the acute-phase response, and resting energy expenditure in cachectic patients with pancreatic cancer. Ann Surg 1994; 219:325.
  35. Kuroda K, Nakashima J, Kanao K, et al. Interleukin 6 is associated with cachexia in patients with prostate cancer. Urology 2007; 69:113.
  36. Johnston AJ, Murphy KT, Jenkinson L, et al. Targeting of Fn14 Prevents Cancer-Induced Cachexia and Prolongs Survival. Cell 2015; 162:1365.
  37. Ling PR, Schwartz JH, Bistrian BR. Mechanisms of host wasting induced by administration of cytokines in rats. Am J Physiol 1997; 272:E333.
  38. Fong Y, Moldawer LL, Marano M, et al. Cachectin/TNF or IL-1 alpha induces cachexia with redistribution of body proteins. Am J Physiol 1989; 256:R659.
  39. Greenberg AS, Nordan RP, McIntosh J, et al. Interleukin 6 reduces lipoprotein lipase activity in adipose tissue of mice in vivo and in 3T3-L1 adipocytes: a possible role for interleukin 6 in cancer cachexia. Cancer Res 1992; 52:4113.
  40. Goshen I, Yirmiya R. Interleukin-1 (IL-1): a central regulator of stress responses. Front Neuroendocrinol 2009; 30:30.
  41. Dinarello CA. Proinflammatory cytokines. Chest 2000; 118:503.
  42. Argilés JM, López-Soriano FJ. The role of cytokines in cancer cachexia. Med Res Rev 1999; 19:223.
  43. Glass DJ. Signalling pathways that mediate skeletal muscle hypertrophy and atrophy. Nat Cell Biol 2003; 5:87.
  44. Hall DT, Ma JF, Marco SD, Gallouzi IE. Inducible nitric oxide synthase (iNOS) in muscle wasting syndrome, sarcopenia, and cachexia. Aging (Albany NY) 2011; 3:702.
  45. Reed SA, Sandesara PB, Senf SM, Judge AR. Inhibition of FoxO transcriptional activity prevents muscle fiber atrophy during cachexia and induces hypertrophy. FASEB J 2012; 26:987.
  46. Costelli P, Reffo P, Penna F, et al. Ca(2+)-dependent proteolysis in muscle wasting. Int J Biochem Cell Biol 2005; 37:2134.
  47. Gelin J, Moldawer LL, Lönnroth C, et al. Role of endogenous tumor necrosis factor alpha and interleukin 1 for experimental tumor growth and the development of cancer cachexia. Cancer Res 1991; 51:415.
  48. Strassmann G, Masui Y, Chizzonite R, Fong M. Mechanisms of experimental cancer cachexia. Local involvement of IL-1 in colon-26 tumor. J Immunol 1993; 150:2341.
  49. Strassmann G, Fong M, Kenney JS, Jacob CO. Evidence for the involvement of interleukin 6 in experimental cancer cachexia. J Clin Invest 1992; 89:1681.
  50. Zaki MH, Nemeth JA, Trikha M. CNTO 328, a monoclonal antibody to IL-6, inhibits human tumor-induced cachexia in nude mice. Int J Cancer 2004; 111:592.
  51. Trikha M, Corringham R, Klein B, Rossi JF. Targeted anti-interleukin-6 monoclonal antibody therapy for cancer: a review of the rationale and clinical evidence. Clin Cancer Res 2003; 9:4653.
  52. Tsujinaka T, Fujita J, Ebisui C, et al. Interleukin 6 receptor antibody inhibits muscle atrophy and modulates proteolytic systems in interleukin 6 transgenic mice. J Clin Invest 1996; 97:244.
  53. Llovera M, García-Martínez C, López-Soriano J, et al. Role of TNF receptor 1 in protein turnover during cancer cachexia using gene knockout mice. Mol Cell Endocrinol 1998; 142:183.
  54. Guttridge DC, Mayo MW, Madrid LV, et al. NF-kappaB-induced loss of MyoD messenger RNA: possible role in muscle decay and cachexia. Science 2000; 289:2363.
  55. Acharyya S, Ladner KJ, Nelsen LL, et al. Cancer cachexia is regulated by selective targeting of skeletal muscle gene products. J Clin Invest 2004; 114:370.
  56. Khan S, Tisdale MJ. Catabolism of adipose tissue by a tumour-produced lipid-mobilising factor. Int J Cancer 1999; 80:444.
  57. Groundwater P, Beck SA, Barton C, et al. Alteration of serum and urinary lipolytic activity with weight loss in cachectic cancer patients. Br J Cancer 1990; 62:816.
  58. Todorov PT, McDevitt TM, Meyer DJ, et al. Purification and characterization of a tumor lipid-mobilizing factor. Cancer Res 1998; 58:2353.
  59. Hirai K, Hussey HJ, Barber MD, et al. Biological evaluation of a lipid-mobilizing factor isolated from the urine of cancer patients. Cancer Res 1998; 58:2359.
  60. Islam-Ali B, Khan S, Price SA, Tisdale MJ. Modulation of adipocyte G-protein expression in cancer cachexia by a lipid-mobilizing factor (LMF). Br J Cancer 2001; 85:758.
  61. Price SA, Tisdale MJ. Mechanism of inhibition of a tumor lipid-mobilizing factor by eicosapentaenoic acid. Cancer Res 1998; 58:4827.
  62. Bing C, Russell S, Becket E, et al. Adipose atrophy in cancer cachexia: morphologic and molecular analysis of adipose tissue in tumour-bearing mice. Br J Cancer 2006; 95:1028.
  63. Rydén M, Agustsson T, Laurencikiene J, et al. Lipolysis--not inflammation, cell death, or lipogenesis--is involved in adipose tissue loss in cancer cachexia. Cancer 2008; 113:1695.
  64. Das SK, Eder S, Schauer S, et al. Adipose triglyceride lipase contributes to cancer-associated cachexia. Science 2011; 333:233.
  65. Llovera M, Garcia-Martinez C, Agell N, et al. Muscle wasting associated with cancer cachexia is linked to an important activation of the ATP-dependent ubiquitin-mediated proteolysis. Int J Cancer 1995; 61:138.
  66. Baracos VE, DeVivo C, Hoyle DH, Goldberg AL. Activation of the ATP-ubiquitin-proteasome pathway in skeletal muscle of cachectic rats bearing a hepatoma. Am J Physiol 1995; 268:E996.
  67. Llovera M, García-Martínez C, Agell N, et al. TNF can directly induce the expression of ubiquitin-dependent proteolytic system in rat soleus muscles. Biochem Biophys Res Commun 1997; 230:238.
  68. Zhang L, Tang H, Kou Y, et al. MG132-mediated inhibition of the ubiquitin-proteasome pathway ameliorates cancer cachexia. J Cancer Res Clin Oncol 2013; 139:1105.
  69. Mitch WE, Goldberg AL. Mechanisms of muscle wasting. The role of the ubiquitin-proteasome pathway. N Engl J Med 1996; 335:1897.
  70. Jatoi A, Alberts SR, Foster N, et al. Is bortezomib, a proteasome inhibitor, effective in treating cancer-associated weight loss? Preliminary results from the North Central Cancer Treatment Group. Support Care Cancer 2005; 13:381.
  71. Zhou X, Wang JL, Lu J, et al. Reversal of cancer cachexia and muscle wasting by ActRIIB antagonism leads to prolonged survival. Cell 2010; 142:531.
  72. Quintás-Cardama A, Verstovsek S. Molecular pathways: Jak/STAT pathway: mutations, inhibitors, and resistance. Clin Cancer Res 2013; 19:1933.
  73. Bonetto A, Aydogdu T, Jin X, et al. JAK/STAT3 pathway inhibition blocks skeletal muscle wasting downstream of IL-6 and in experimental cancer cachexia. Am J Physiol Endocrinol Metab 2012; 303:E410.
  74. Hurwitz HI, Uppal N, Wagner SA, et al. Randomized, Double-Blind, Phase II Study of Ruxolitinib or Placebo in Combination With Capecitabine in Patients With Metastatic Pancreatic Cancer for Whom Therapy With Gemcitabine Has Failed. J Clin Oncol 2015; 33:4039.
  75. Stephens NA, Gallagher IJ, Rooyackers O, et al. Using transcriptomics to identify and validate novel biomarkers of human skeletal muscle cancer cachexia. Genome Med 2010; 2:1.
  76. Theologides A, Ehlert J, Kennedy BJ. The calorie intake of patients with advanced cancer. Minn Med 1976; 59:526.
  77. Steinbach S, Hummel T, Böhner C, et al. Qualitative and quantitative assessment of taste and smell changes in patients undergoing chemotherapy for breast cancer or gynecologic malignancies. J Clin Oncol 2009; 27:1899.
  78. Bernhardson BM, Tishelman C, Rutqvist LE. Self-reported taste and smell changes during cancer chemotherapy. Support Care Cancer 2008; 16:275.
  79. Temmel AF, Quint C, Schickinger-Fischer B, et al. Characteristics of olfactory disorders in relation to major causes of olfactory loss. Arch Otolaryngol Head Neck Surg 2002; 128:635.
  80. Levine JA, Morgan MY. Preservation of macronutrient preferences in cancer anorexia. Br J Cancer 1998; 78:579.
  81. Kwang AY, Kandiah M. Objective and subjective nutritional assessment of patients with cancer in palliative care. Am J Hosp Palliat Care 2010; 27:117.
  82. McGeer AJ, Detsky AS, O'Rourke K. Parenteral nutrition in cancer patients undergoing chemotherapy: a meta-analysis. Nutrition 1990; 6:233.
  83. Kir S, White JP, Kleiner S, et al. Tumour-derived PTH-related protein triggers adipose tissue browning and cancer cachexia. Nature 2014; 513:100.
  84. Cohn SH, Gartenhaus W, Sawitsky A, et al. Compartmental body composition of cancer patients by measurement of total body nitrogen, potassium, and water. Metabolism 1981; 30:222.
  85. Keys A, Brozek J, Henschel A, et al. The Biology of Human Starvation, University of Minnesota Press, St. Paul 1950.
  86. Rofe AM, Bourgeois CS, Coyle P, et al. Altered insulin response to glucose in weight-losing cancer patients. Anticancer Res 1994; 14:647.
  87. Tracey KJ, Cerami A. Tumor necrosis factor in the malnutrition (cachexia) of infection and cancer. Am J Trop Med Hyg 1992; 47:2.
  88. Hardardóttir I, Grünfeld C, Feingold KR. Effects of endotoxin and cytokines on lipid metabolism. Curr Opin Lipidol 1994; 5:207.
  89. Hofmann C, Lorenz K, Braithwaite SS, et al. Altered gene expression for tumor necrosis factor-alpha and its receptors during drug and dietary modulation of insulin resistance. Endocrinology 1994; 134:264.
  90. Peraldi P, Xu M, Spiegelman BM. Thiazolidinediones block tumor necrosis factor-alpha-induced inhibition of insulin signaling. J Clin Invest 1997; 100:1863.
  91. Hotamisligil GS, Johnson RS, Distel RJ, et al. Uncoupling of obesity from insulin resistance through a targeted mutation in aP2, the adipocyte fatty acid binding protein. Science 1996; 274:1377.
  92. Zinman B, Hanley AJ, Harris SB, et al. Circulating tumor necrosis factor-alpha concentrations in a native Canadian population with high rates of type 2 diabetes mellitus. J Clin Endocrinol Metab 1999; 84:272.
  93. Pisters PW, Pearlstone DB. Protein and amino acid metabolism in cancer cachexia: investigative techniques and therapeutic interventions. Crit Rev Clin Lab Sci 1993; 30:223.
  94. Rhondali W, Chisholm GB, Daneshmand M, et al. Association between body image dissatisfaction and weight loss among patients with advanced cancer and their caregivers: a preliminary report. J Pain Symptom Manage 2013; 45:1039.
  95. Oberholzer R, Hopkinson JB, Baumann K, et al. Psychosocial effects of cancer cachexia: a systematic literature search and qualitative analysis. J Pain Symptom Manage 2013; 46:77.
  96. Del Río MI, Shand B, Bonati P, et al. Hydration and nutrition at the end of life: a systematic review of emotional impact, perceptions, and decision-making among patients, family, and health care staff. Psychooncology 2012; 21:913.
  97. Reuben DB, Mor V, Hiris J. Clinical symptoms and length of survival in patients with terminal cancer. Arch Intern Med 1988; 148:1586.
  98. Dewys WD, Begg C, Lavin PT, et al. Prognostic effect of weight loss prior to chemotherapy in cancer patients. Eastern Cooperative Oncology Group. Am J Med 1980; 69:491.
  99. Ambrus JL, Ambrus CM, Mink IB, Pickren JW. Causes of death in cancer patients. J Med 1975; 6:61.
  100. Martin L, Birdsell L, Macdonald N, et al. Cancer cachexia in the age of obesity: skeletal muscle depletion is a powerful prognostic factor, independent of body mass index. J Clin Oncol 2013; 31:1539.
  101. Blauwhoff-Buskermolen S, Versteeg KS, de van der Schueren MA, et al. Loss of Muscle Mass During Chemotherapy Is Predictive for Poor Survival of Patients With Metastatic Colorectal Cancer. J Clin Oncol 2016; 34:1339.
  102. Shachar SS, Williams GR, Muss HB, Nishijima TF. Prognostic value of sarcopenia in adults with solid tumours: A meta-analysis and systematic review. Eur J Cancer 2016; 57:58.
  103. Morishita S, Kaida K, Tanaka T, et al. Prevalence of sarcopenia and relevance of body composition, physiological function, fatigue, and health-related quality of life in patients before allogeneic hematopoietic stem cell transplantation. Support Care Cancer 2012; 20:3161.
  104. Capuano G, Gentile PC, Bianciardi F, et al. Prevalence and influence of malnutrition on quality of life and performance status in patients with locally advanced head and neck cancer before treatment. Support Care Cancer 2010; 18:433.
  105. Wheeler DA, Gibert CL, Launer CA, et al. Weight loss as a predictor of survival and disease progression in HIV infection. Terry Beirn Community Programs for Clinical Research on AIDS. J Acquir Immune Defic Syndr Hum Retrovirol 1998; 18:80.
  106. Guenter P, Muurahainen N, Simons G, et al. Relationships among nutritional status, disease progression, and survival in HIV infection. J Acquir Immune Defic Syndr 1993; 6:1130.
  107. Martin L, Senesse P, Gioulbasanis I, et al. Diagnostic criteria for the classification of cancer-associated weight loss. J Clin Oncol 2015; 33:90.