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Cancer Cachexia (CC)

  • Nagi B. Kumar
Chapter

Abstract

Cancer cachexia (CC) is a pathological loss of striated muscle (skeletal and cardiac) and fat stores, manifesting in the cardinal features of emaciation, weakness affecting functional status, impaired immune system, metabolic dysfunction, and poor quality of life.

Keywords

Lean Body Mass Proteasome Activity Cancer Cachexia Annual Effective Dose Total Bone Mineral Density 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. 1.
    Ross PJ, Ashley S, Norton A, Priest K, Waters JS, Eisen T et al (2004) Do patients with weight loss have a worse outcome when undergoing chemotherapy for lung cancers? Br J Cancer 90:1905–1911PubMedCrossRefGoogle Scholar
  2. 2.
    Jatoi A (2008) Weight loss in patient with advanced cancer: effects, causes, and potential management. Curr Opin Support Palliat Care 2(1):45–48PubMedCrossRefGoogle Scholar
  3. 3.
    Evans WJ, Morley JE, Argilés J, Bales C, Baracos V, Guttridge D, Jatoi A et al (2008) Cachexia: a new definition. Clin Nutr 27(6):793–799, Epud 2008 Aug 21. PMID: 18718696PubMedCrossRefGoogle Scholar
  4. 4.
    Behl D, Jatoi A (2007) Pharmacological options for advanced cancer patients with loss of appetite and weight. Expert Opin Pharmacother 8(8):1085–1090PubMedCrossRefGoogle Scholar
  5. 5.
    Morley JE (2002) Pathophysiology of anorexia. Clin Geriatr Med 18(4):661–673, v. Review. PMID: 12608495PubMedCrossRefGoogle Scholar
  6. 6.
    Melstrom LG, Melstrom KA Jr, Ding XZ, Adrian TE (2007) Mechanisms of skeletal muscle degradation and its therapy in cancer cachexia. Histol Histopathol 22(7):805–814PubMedGoogle Scholar
  7. 7.
    Mantovani G, Macciò A, Madeddu C, Serpe R, Massa E, Dessì M, Panzone F, Contu P (2010) Randomized phase III clinical trial of five different arms of treatment in 332 patients with cancer cachexia. Oncologist 15(2):200–211, Epub 2010 Feb 15PubMedCrossRefGoogle Scholar
  8. 8.
    Giacosa A, Rondanelli M (2008) Fish oil and treatment of cancer cachexia. Genes Nutr 3(1):25–28PubMedCrossRefGoogle Scholar
  9. 9.
    Bosaeus I (2008) Nutritional support in multimodal therapy for CC. Support Care Cancer 16(5):447–451, Epub 2008 Jan 15. PMID: 18196284PubMedCrossRefGoogle Scholar
  10. 10.
    Blum B, Omlin A, Fearon K, Baracos V, Radbruch L, Kaasa S, Strasser F, European Palliative Care Research Collaborative (2010) Evolving classification systems for CC: ready for clinical practice? Support Care Cancer 18(3):273–279, PMID: 20076976PubMedCrossRefGoogle Scholar
  11. 11.
    Bozzetti F, Mariani L (2009) Defining and classifying CC: a proposal by SCRINIO Working Group. JPEN J Parenter Enteral Nutr 33(4):361–367, Epub 2008 Dec 24. PMID: 19109514PubMedCrossRefGoogle Scholar
  12. 12.
    Deans DA, Tan BH, Wigmore SJ, Ross JA, de Beaux AC, Paterson-Brown S, Feron KV (2009) The influence of systemic inflammation, dietary intake and stage of disease on rate of weight loss in patients with gastro-esophageal cancer. Br J Cancer 100(1):63–69PubMedCrossRefGoogle Scholar
  13. 13.
    Hamerman D (2002) Molecular-based therapeutic approaches in treatment of anorexia of aging and CC. J Gerontol A Biol Sci Med Sci 57(8):M511–M518, Review. PMID: 12145364PubMedCrossRefGoogle Scholar
  14. 14.
    Dewys WD, Begg C, Lavin PT, Band PR, Bennett JM, Bertino JR, Cohen MH, Douglass HO Jr, Engstrom PF, Ezdinli EZ, Horton J, Johnson GJ, Moertel CG, Oken MM, Perlina C, Rosenbaum C, Silverstein MN, Skeel RT, Sponzo RW, Tormey DC (1980) Prognostic effect of weight loss prior to chemotherapy in cancer patients. Eastern Cooperative Oncology Group. Am J Med 69:491–497, PMID: 7424938PubMedCrossRefGoogle Scholar
  15. 15.
    McMillan DC (2009) Systemic inflammation, nutritional status and survival in patients with cancer. Curr Opin Clin Nutr Metab Care 12(3):223–226PubMedCrossRefGoogle Scholar
  16. 16.
    Morley JE (2003) Anorexia and weight loss in older persons. J Gerontol A Biol Sci Med Sci 58(2):131–137PubMedCrossRefGoogle Scholar
  17. 17.
    Kim W, McMurray DN, Chapkin RS (2010) n − 3 polyunsaturated fatty acids-physiological relevance of dose. Prostaglandins Leukot Essent Fatty Acids 82(4–6):155–158, Epub 2010 Feb 25. ReviewPubMedCrossRefGoogle Scholar
  18. 18.
    Barton BE (2001) IL-6-like cytokines and CC: consequences of chronic inflammation. Immunol Res 23(1):41–58, Review. PMID: 11417859PubMedCrossRefGoogle Scholar
  19. 19.
    Mantovani G, Madeddu C, Gramignano G, Ferreli L, Massa E, Contu P, Serpe R (2004) Association of serum IL-6 levels with comprehensive geriatric assessment variables in a population of elderly cancer patients. Oncol Rep 11(1):197–206PubMedGoogle Scholar
  20. 20.
    Barber MD, Wigmore SJ, Ross JA, Fearon KC, Tisdale MJ (1998) Proinflammatory cytokines, nutritional support, and the cachexia syndrome: interactions and therapeutic options. Cancer 82(5):1000PubMedCrossRefGoogle Scholar
  21. 21.
    Evans WJ (2010) Skeletal muscle loss: cachexia, sarcopenia, and inactivity. Am J Clin Nutr 91(4):1123S–1127S, Epub 2010 Feb 17PubMedCrossRefGoogle Scholar
  22. 22.
    Pickering WP, Price SR, Bircher G, Marinovic AC, Mitch WE, Walls J (2002) Nutrition in CAPD: serum bicarbonate and the ubiquitin-proteasome system in muscle. Kidney Int 61:1286–1292PubMedCrossRefGoogle Scholar
  23. 23.
    Du J, Wang X, Miereles C et al (2004) Activation of caspase-3 is an initial step triggering accelerated muscle proteolysis in catabolic conditions. J Clin Invest 113:115–123PubMedGoogle Scholar
  24. 24.
    Mantovani G, Maccio A, Mura L, Massa E, Mudu MC, Mulas C et al (2000) Serum levels of leptin and proinflammatory cytokines in patients with advanced-stage cancer at different sites. J Mol Med 78(10):554–561PubMedCrossRefGoogle Scholar
  25. 25.
    Deans DA, Wigmore SJ, Gilmour H, Tisdale MJ, Fearon KC, Ross JA (2008) Expression of the proteolysis-inducing factor core peptide mRNA is upregulated in both tumour and adjacent normal tissue in gastro-esophageal malignancy. Br J Cancer 98(1):242; author reply 243. PMCID: PMC2361198CrossRefGoogle Scholar
  26. 26.
    Wigmore SJ, Todorov PT, Barber MD, Ross JA, Tisdale MJ, Fearon KC (2000) Characteristics of patients with pancreatic cancer expressing a novel cancer cachectic factor. Br J Surg 87(1):53–58PubMedCrossRefGoogle Scholar
  27. 27.
    Whitehouse AS, Tisdale MJ (2003) Increased expression of the ubiquitin-proteasome pathway in murine myotubes by proteolysis-inducing factor (PIF) is associated with activation of the transcription factor NF-kappaB. Br J Cancer 89(6):1116–1122PubMedCrossRefGoogle Scholar
  28. 28.
    Mitch WE, Price SR (2001) Transcription factors and muscle cachexia: is there a therapeutic target? Lancet 357(9258):734–735PubMedCrossRefGoogle Scholar
  29. 29.
    Ciechanover A, Orian A, Schwartz AL (2000) The ubiquitin-mediated proteolytic pathway: mode of action and clinical implications. J Cell Biochem Suppl 34:40–51PubMedCrossRefGoogle Scholar
  30. 30.
    Voges D, Zwickl P, Baumeister W (1999) The 26S proteasome: a molecular machine designed for controlled proteolysis. Annu Rev Biochem 68:1015–1068PubMedCrossRefGoogle Scholar
  31. 31.
    Chen S, Fribley A, Wang CY (2002) Potentiation of tumor necrosis factor-mediated apoptosis of oral squamous cell carcinoma cells by adenovirus-mediated gene transfer of NF-kappaB inhibitor. J Dent Res 81:98–102PubMedCrossRefGoogle Scholar
  32. 32.
    Ghosh S, Karin M (2002) Missing pieces in the NF-kappaB puzzle. Cell 109 Suppl:S81–S96PubMedCrossRefGoogle Scholar
  33. 33.
    Fearon KC, Van Meyenfeldt MF, Moses AG, Van Geenen R, Roy A, Gouma DJ et al (2003) Effect of a protein and energy dense N − 3 fatty acid enriched oral supplement on loss of weight and lean tissue in CC: a randomised double blind trial. Gut 52(10):1479–1486, PMCID: PMC1773823PubMedCrossRefGoogle Scholar
  34. 34.
    Maltoni M, Fabbri L, Nanni O, Scarpi E, Pezzi L, Flamini E et al (1997) Serum levels of tumor necrosis factor alpha and other cytokines do not correlate with weight loss and anorexia in cancer patients. Support Care Cancer 5(2):130–135; comments in Support Care Cancer. 1997;5(5):422–423. PMID: 9069613PubMedCrossRefGoogle Scholar
  35. 35.
    Whitehouse AS, Khal J, Tisdale MJ (2003) Induction of protein catabolism in myotubes by 15(S)-hydroxyeicosatetraenoic acid through increased expression of the ubiquitin-proteasome pathway. Br J Cancer 89(4):737–745, PMID: 12915888PubMedCrossRefGoogle Scholar
  36. 36.
    Das SK, Eder S, Schauer S, Diwoky C, Temmel H, Guertl B, Gorkiewicz G, Tamilarasan KP, Kumari P, Trauner M, Zimmermann R, Vesely P, Haemmerle G, Zechner R, Hoefler G (2011) Adipose triglyceride lipase contributes to cancer-associated cachexia. Science 333(6039):233–238, Epub 2011 Jun 16PubMedCrossRefGoogle Scholar
  37. 37.
    Fearon KC (2011) Cancer cachexia and fat-muscle physiology. N Engl J Med 365(6):565–567PubMedCrossRefGoogle Scholar
  38. 38.
    Acharyya S, Ladner KJ, Nelsen LL et al (2004) Cancer cachexia is regulated by selective ­targeting of skeletal muscle gene products. J Clin Invest 114:370–378PubMedGoogle Scholar
  39. 39.
    Peterson JM, Bakkar N, Guttridge DC (2011) NF-κB signaling in skeletal muscle health and disease. Curr Top Dev Biol 96:85–119PubMedCrossRefGoogle Scholar
  40. 40.
    Guttridge DC, Mayo MW, Madrid LV, Wang CY, Baldwin AS Jr (2000) NF-kappaB-induced loss of MyoD messenger RNA: possible role in muscle decay and cachexia. Science 289(5488):2363–2366PubMedCrossRefGoogle Scholar
  41. 41.
    Attaix D, Combaret L, Béchet D, Taillandier D (2008) Role of the ubiquitin-proteasome pathway in muscle atrophy in cachexia. Curr Opin Support Palliat Care 2(4):262–266PubMedCrossRefGoogle Scholar
  42. 42.
    Fukuda T, Sumi T, Nobeyama H, Yoshida H, Matsumoto Y, Yasui T, Honda K, Ishiko O (2009) Multiple organ failure of tumor-bearing rabbits in cancer cachexia is caused by apoptosis of normal organ cells. Int J Oncol 34(1):61–67PubMedGoogle Scholar
  43. 43.
    Argilés JM, López-Soriano FJ, Busquets S (2007) Mechanisms to explain wasting of muscle and fat in cancer cachexia. Curr Opin Support Palliat Care 1(4):293–298PubMedCrossRefGoogle Scholar
  44. 44.
    Belizário JE, Lorite MJ, Tisdale MJ (2001) Cleavage of caspases-1, -3, -6, -8 and -9 substrates by proteases in skeletal muscles from mice undergoing cancer cachexia. Br J Cancer 84(8):1135–1140PubMedCrossRefGoogle Scholar
  45. 45.
    Adamsen L, Quist M, Andersen C, Møller T, Herrstedt J, Kronborg D et al (2009) Effect of a multimodal high intensity exercise intervention in cancer patients undergoing chemotherapy: randomized controlled trial. BMJ 339:b3410PubMedCrossRefGoogle Scholar
  46. 46.
    Sun LC, Chu KS, Cheng SC, Lu CY, Kuo CH, Hsieh JS et al (2009) Preoperative serum carcinoembryonic antigen, albumin and age are supplementary to UICC staging systems in predicting survival for colorectal cancer patients undergoing surgical treatment. BMC Cancer 9:288PubMedCrossRefGoogle Scholar
  47. 47.
    Walsh D, Nelson KA, Mahmoud FA (2003) Established and potential therapeutic applications of cannabinoids in oncology. Support Care Cancer 11(3):137–143, Epub 2002 Aug 21. Review. PMID: 12618922PubMedGoogle Scholar
  48. 48.
    Ghosh S, Karin M (2002) Missing pieces in the NF-kappaB puzzle. Cell 109(Suppl):S81–S96PubMedCrossRefGoogle Scholar
  49. 49.
    Reid BN, Ables GP, Otlivanchik OA, Schoiswohl G, Zechner R, Blaner WS, Goldberg IJ, Schwabe RF, Chua SC Jr, Huang LS (2008) Hepatic overexpression of hormone-sensitive lipase and adipose triglyceride lipase promotes fatty acid oxidation, stimulates direct release of free fatty acids, and ameliorates steatosis. J Biol Chem 283(19):13087–13099, Epub 2008 Mar 12PubMedCrossRefGoogle Scholar
  50. 50.
    Lass A, Zimmermann R, Oberer M, Zechner R (2011) Lipolysis - a highly regulated multi-enzyme complex mediates the catabolism of cellular fat stores. Prog Lipid Res 50(1):14–27, Epub 2010 Nov 16. ReviewPubMedCrossRefGoogle Scholar
  51. 51.
    Wölkart G, Schrammel A, Dörffel K, Haemmerle G, Zechner R, Mayer B (2011) Cardiac dysfunction in adipose triglyceride lipase deficiency: treatment with a PPARα agonist. Br J Pharmacol. doi:10.1111/j.1476-5381.2011.01490.xGoogle Scholar
  52. 52.
    Wu JW, Wang SP, Alvarez F, Casavant S, Gauthier N, Abed L, Soni KG, Yang G, Mitchell GA (2011) Deficiency of liver adipose triglyceride lipase in mice causes progressive hepatic steatosis. Hepatology 54(1):122–132PubMedCrossRefGoogle Scholar
  53. 53.
    Schoiswohl G, Schweiger M, Schreiber R, Gorkiewicz G, Preiss-Landl K, Taschler U, Zierler KA, Radner FP, Eichmann TO, Kienesberger PC, Eder S, Lass A, Haemmerle G, Alsted TJ, Kiens B, Hoefler G, Zechner R, Zimmermann R (2010) Adipose triglyceride lipase plays a key role in the supply of the working muscle with fatty acids. J Lipid Res 51(3):490–499, Epub 2009 Nov 25PubMedCrossRefGoogle Scholar
  54. 54.
    Spencer L, Mann C, Metcalfe M, Webb M, Pollard C, Spencer D, Berry D, Steward W, Dennison A (2009) The effect of omega-3 FAs on tumour angiogenesis and their therapeutic potential. Eur J Cancer 45(12):2077–2086, Epub 2009 Jun 1PubMedCrossRefGoogle Scholar
  55. 55.
    Smith GI, Atherton P, Reeds DN, Mohammed BS, Rankin D, Rennie MJ, Mittendorfer B (2011) Dietary omega-3 fatty acid supplementation increases the rate of muscle protein synthesis in older adults: a randomized controlled trial. Am J Clin Nutr 93(2):402–412, Epub 2010 Dec 15PubMedCrossRefGoogle Scholar
  56. 56.
    Magee P, Pearson S, Allen J (2008) The omega-3 fatty acid, eicosapentaenoic acid (EPA), prevents the damaging effects of tumour necrosis factor (TNF)-alpha during murine skeletal muscle cell differentiation. Lipids Health Dis 7:24PubMedCrossRefGoogle Scholar
  57. 57.
    Kumar NB, Kazi A, Smith T, Crocker T, Yu D, Reich RR, Reddy K, Hastings S, Exterman M, Balducci L, Dalton K, Bepler G (2010) Cancer cachexia: traditional therapies and novel molecular mechanism-based approaches to treatment. Curr Treat Options Oncol 11(3–4):107–117, ReviewPubMedCrossRefGoogle Scholar
  58. 58.
    Mantovani G, Macciò A, Madeddu C, Gramignano G, Serpe R, Massa E et al (2008) Randomized phase III clinical trial of five different arms of treatment for patients with CC: interim results. Nutrition 24(4):305–313, Epub 2008 Feb 11PubMedCrossRefGoogle Scholar
  59. 59.
    Dewey A, Baughan C, Dean T, Higgins B, Johnson I (2007) Eicosapentaenoic acid (EPA, an omega-3 fatty acid from fish oils) for the treatment of CC. Cochrane Database Syst Rev 24(1):CD004597, same as 33Google Scholar
  60. 60.
    Lee SJ, McPherron AC (2001) Regulation of myostatin activity and muscle growth. Proc Natl Acad Sci USA 98(16):9306–9311PubMedCrossRefGoogle Scholar
  61. 61.
    Siriett V, Salerno MS, Berry C, Nicholas G, Bower R, Kambadur R, Sharma M (2007) Antagonism of myostatin enhances muscle regeneration during sarcopenia. Mol Ther 15(8):1463–1470PubMedCrossRefGoogle Scholar
  62. 62.
    Bogdanovich S, Perkins KJ, Krag TO, Whittemore LA, Khurana TS (2005) Myostatin propeptide-mediated amelioration of dystrophic pathophysiology. FASEB J 19(6):543–549PubMedCrossRefGoogle Scholar
  63. 63.
    Bogdanovich S, Krag TO, Barton ER, Morris LD, Whittemore LA, Ahima RS, Khurana TS (2002) Functional improvement of dystrophic muscle by myostatin blockade. Nature 420(6914):418–421PubMedCrossRefGoogle Scholar
  64. 64.
    Blackburn GL, Moldawer LL, Usui S, Bothe A Jr, O’Keefe SJ, Bistrian BR (1979) Branched chain amino acid administration and metabolism during starvation, injury, and infection. Surgery 86(2):307–315PubMedGoogle Scholar
  65. 65.
    Hart DW, Wolf SE, Herndon DN et al (2002) Energy expenditure and caloric balance after burn: increased feeding leads to fat rather than lean mass accretion. Ann Surg 235:152–161PubMedCrossRefGoogle Scholar
  66. 66.
    Couch M, Lai V, Cannon T, Guttridge D, Zanation A, George J, Hayes DN, Zeisel S, Shores C (2007) Cancer cachexia syndrome in head and neck cancer patients: part I. Diagnosis, impact on quality of life and survival, and treatment. Head Neck 29(4):401–411, PMID: 17285641PubMedCrossRefGoogle Scholar
  67. 67.
    Fearon KC, von Meyenfeldt M, Moses AG, Van Geenen R, Roy A, Gouma DJ, Giacosa A, Van Gossum A, Bauer J, Barber MD, Aaronson NK, Voss AC, Tisdale MJ (2003) Effect of a protein and energy dense n − 3 fatty acid enriched oral supplement on weight and lean tissue in CC: a randomized double blind trial. Gut 52(10):1479–1486, PMCID: PMC1773823PubMedCrossRefGoogle Scholar
  68. 68.
    Barber MD, Fearon KC, Tisdale MJ, McMillan DC, Ross JA (2001) Effect of a fish oil-enriched nutritional supplement on metabolic mediators in patients with pancreatic CC. Nutr Cancer 40(2):118–124PubMedCrossRefGoogle Scholar
  69. 69.
    Fearon KC, Barber MD, Moses AG, Ahmedzai SH, Taylor GS, Tisdale MJ, Murray GD (2006) Double-blind, placebo-controlled, randomized study of eicosapentaenoic acid diester in patients with CC. J Clin Oncol 24(21):3401–3407PubMedCrossRefGoogle Scholar
  70. 70.
    Karcic E, Philpot C, Morley JE (2002) Treating malnutrition with megestrol acetate: literature review and review of our experience. J Nutr Health Aging 6(3):191–200, Review. PMID: 12152625PubMedGoogle Scholar
  71. 71.
    Morley JE (2002) Orexigenic and anabolic agents. Clin Geriatr Med 18(4):853–866, Review. PMID: 12608509PubMedCrossRefGoogle Scholar
  72. 72.
    Desport JC, Gory-Dalabaere G, Blanc-Vincent MP, Bachmann P, Béal J, Benamouzig R, Colomb V, Kere D, Melchior JC, Nitenberg G, Raynard B, Schneider S, Senesse P, FNCLCC (2003) Standards, options and recommendations for the use of appetite stimulants in oncology (2000). Br J Cancer 89 Suppl 1:S98–S100, PMID: 12915909PubMedCrossRefGoogle Scholar
  73. 73.
    Kumar NB, Hopkins K (2007) A retrospective study of nutritional supplementation and appetite stimulants in the treatment of Cancer Cachexia. Abstract. Proceedings of Research Day, Moffitt Cancer CenterGoogle Scholar
  74. 74.
    Al-Majid S, Waters H (2008) The biological mechanisms of cancer-related skeletal muscle wasting: the role of progressive resistance exercise. Biol Res Nurs 10(1):7–20PubMedCrossRefGoogle Scholar
  75. 75.
    Trutschnigg B, Kilgour RD, Reinglas J et al (2008) Precision and reliability of strength. (Jamar vs. Biodex handgrip) and body composition (dual-energy X-ray absorptiometry vs bioimpedance analysis) measurements in advanced cancer patients. Appl Physiol Nutr Metab 33:1232–1239PubMedCrossRefGoogle Scholar
  76. 76.
    Guerra LT, Rosa AR, Romani RF, Gurski RR, Schirmer CC, Kruel CD (2009) Serum transferrin and serum prealbumin as markers of response to nutritional support in patients with esophageal cancer. Nutr Hosp 24(2):241–242, PMID: 19593499PubMedGoogle Scholar
  77. 77.
    Neyra NR, Hakim RM, Shyr Y, Ikizler TA (2000) Serum transferrin and serum prealbumin are early predictors of serum albumin in chronic hemodialysis patients. J Ren Nutr 10(4):184–190PubMedCrossRefGoogle Scholar
  78. 78.
    Beguin Y (2003) Soluble transferrin receptor for the evaluation of erythropoiesis and iron status. Clin Chim Acta 329:9–22PubMedCrossRefGoogle Scholar
  79. 79.
    Garratt AM, Ruta DA, Abdalla MI, Buckingham JK, Russell IT (1993) The SF36 health survey questionnaire: an outcome measure suitable for routine use within the NHS? BMJ 306(6890):1440–1444PubMedCrossRefGoogle Scholar

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© Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  1. 1.University of South FloridaTampaUSA

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