Cancer cachexia: mechanisms and clinical implications

Claire L Donohoe, Aoife M Ryan, John V Reynolds, Claire L Donohoe, Aoife M Ryan, John V Reynolds

Abstract

Cachexia is a multifactorial process of skeletal muscle and adipose tissue atrophy resulting in progressive weight loss. It is associated with poor quality of life, poor physical function, and poor prognosis in cancer patients. It involves multiple pathways: procachectic and proinflammatory signals from tumour cells, systemic inflammation in the host, and widespread metabolic changes (increased resting energy expenditure and alterations in metabolism of protein, fat, and carbohydrate). Whether it is primarily driven by the tumour or as a result of the host response to the tumour has yet to be fully elucidated. Cachexia is compounded by anorexia and the relationship between these two entities has not been clarified fully. Inconsistencies in the definition of cachexia have limited the epidemiological characterisation of the condition and there has been slow progress in identifying therapeutic agents and trialling them in the clinical setting. Understanding the complex interplay of tumour and host factors will uncover new therapeutic targets.

Figures

Figure 1
Figure 1
Clinical consequences of cancer cachexia.

References

    1. Tisdale MJ. Mechanisms of cancer cachexia. Physiological Reviews. 2009;89(2):381–410.
    1. Dewys WD, Begg C, Lavin PT, et al. Prognostic effect of weight loss prior to chemotherapy in cancer patients. Eastern Cooperative Oncology Group. American Journal of Medicine. 1980;69:491–497.
    1. Maltoni M, Caraceni A, Brunelli C, et al. Prognostic factors in advanced cancer patients: evidence-based clinical recommendations—a study by the steering committee of the european association for palliative care. Journal of Clinical Oncology. 2005;23(25):6240–6248.
    1. O’Gorman P, McMillan DC, McArdle CS. Longitudinal study of weight, appetite, performance status, and inflammation in advanced gastrointestinal cancer. Nutrition and Cancer. 1999;35(2):127–129.
    1. Tisdale MJ. Cachexia in cancer patients. Nature Reviews Cancer. 2002;2(11):862–871.
    1. Evans WJ, Morley JE, Argilés J, et al. Cachexia: a new definition. Clinical Nutrition. 2008;27(6):793–799.
    1. MacDonald N, Easson AM, Mazurak VC, Dunn GP, Baracos VE. Understanding and managing cancer cachexia. Journal of the American College of Surgeons. 2003;197(1):143–161.
    1. Fearon KC, Voss AC, Hustead DS. Definition of cancer cachexia: effect of weight loss, reduced food intake, and systemic inflammation on functional status and prognosis. American Journal of Clinical Nutrition. 2006;83(6):1345–1350.
    1. Bruera E. ABC of palliative care: anorexia, cachexia, and nutrition. British Medical Journal. 1997;315(7117):1219–1222.
    1. Fox KM, Brooks JM, Gandra SR, Markus R, Chiou CF. Estimation of cachexia among cancer patients based on four definitions. Journal of Oncology. 2009;2009 Article ID 693458.
    1. Strasser F. Diagnostic criteria of cachexia and their assessment: decreased muscle strength and fatigue. Current Opinion in Clinical Nutrition and Metabolic Care. 2008;11(4):417–421.
    1. Argilés JM, Moore-Carrasco R, Fuster G, Busquets S, López-Soriano FJ. Cancer cachexia: the molecular mechanisms. International Journal of Biochemistry and Cell Biology. 2003;35(4):405–409.
    1. Moley JF, Aamodt R, Rumble W. Body cell mass in cancer-bearing and anorexic patients. Journal of Parenteral and Enteral Nutrition. 1987;11(3):219–222.
    1. Khal J, Hine AV, Fearon KCH, Dejong CHC, Tisdale MJ. Increased expression of proteasome subunits in skeletal muscle of cancer patients with weight loss. International Journal of Biochemistry and Cell Biology. 2005;37(10):2196–2206.
    1. DeJong CH, Busquets S, Moses AG, et al. Systemic inflammation correlates with increased expression of skeletal muscle ubiquitin but not uncoupling proteins in cancer cachexia. Oncology Reports. 2005;14(1):257–263.
    1. Bosutti A, Toigo G, Ciocchi B, Situlin R, Guarnieri G, Biolo G. Regulation of muscle cathepsin B proteolytic activity in protein-depleted patients with chronic diseases. Clinical Nutrition. 2002;21(5):373–378.
    1. Busquets S, García-Martínez C, Alvarez B, Carbó N, López-Soriano FJ, Argilés JM. Calpain-3 gene expression is decreased during experimental cancer cachexia. Biochimica et Biophysica Acta. 2000;1475(1):5–9.
    1. McMillan DC, Preston T, Fearon KCH, Burns HJG, Slater C, Shenkin A. Protein synthesis in cancer patients with inflammatory response: Investigations with [N]glycine. Nutrition. 1994;10(3):232–240.
    1. Tisdale MJ. Cancer cachexia. Current Opinion in Gastroenterology. 2010;26(2):146–151.
    1. Hyltander A, Drott C, Korner U, Sandstrom R, Lundholm K. Elevated energy expenditure in cancer patients with solid tumours. European Journal of Cancer. 1991;27(1):9–15.
    1. McMillan DC. Systemic inflammation, nutritional status and survival in patients with cancer. Current Opinion in Clinical Nutrition and Metabolic Care. 2009;12(3):223–226.
    1. Mantovani G, Macciò A, Madeddu C, et al. Randomized phase III clinical trial of five different arms of treatment for patients with cancer cachexia: interim results. Nutrition. 2008;24(4):305–313.
    1. Willox JC, Corr J, Shaw J. Prednisolone as an appetite stimulant in patients with cancer. British Medical Journal. 1984;288(6410):p. 27.
    1. Moertel CG, Schutt AJ, Reitemeier RJ, Hahn RG. Corticosteroid therapy of preterminal gastrointestinal cancer. Cancer. 1974;33(6):1607–1609.
    1. Bruera E, Roca E, Cedaro L. Action of oral methylprednisolone in terminal cancer patients: a prospective randomized double-blind study. Cancer Treatment Reports. 1985;69(7-8):751–754.
    1. Chlebowski RT, Herrold J, Ali I. Influence on nandrolone decanoate on weight loss in advanced non-small cell lung cancer. Cancer. 1986;58(1):183–186.
    1. Lundholm K, Körner U, Gunnebo L, et al. Insulin treatment in cancer cachexia: effects on survival, metabolism, and physical functioning. Clinical Cancer Research. 2007;13(9):2699–2706.
    1. Agteresch HJ, et al. Beneficial effects of adenosine triphosphate on nutritional status in advanced lung cancer patients: a randomized clinical trial. Nutrition in Clinical Practice. 2004;19(4):p. 413.
    1. Berenstein EG, Ortiz Z. Megestrol acetate for the treatment of anorexia-cachexia syndrome. Cochrane Database of Systematic Reviews. 2005;(2) Article ID CD004310.
    1. Mantovani G, Macciò A, Esu S, et al. Medroxyprogesterone acetate reduces the In vitro production of cytokines and serotonin involved in anorexia/cachexia and emesis by peripheral blood mononuclear cells of cancer patients. European Journal of Cancer Part A. 1997;33(4):602–607.
    1. Jatoi A, Windschitl HE, Loprinzi CL, et al. Dronabinol versus megestrol acetate versus combination therapy for cancer-associated anorexia: a North Central Cancer Treatment Group study. Journal of Clinical Oncology. 2002;20(2):567–573.
    1. Strasser F, Luftner D, Possinger K, et al. Comparison of orally administered cannabis extract and delta-9- tetrahydrocannabinol in treating patients with cancer-related anorexia-cachexia syndrome: a multicenter, phase III, randomized, double-blind, placebo-controlled clinical trial from the Cannabis-In-Cachexia-Study-Group. Journal of Clinical Oncology. 2006;24(21):3394–3400.
    1. Argils JM, Meijsing H, Pallars-Trujillo J, Guirao X, Lpez-Soriano FJ. Cancer cachexia: a therapeutic approach. Medicinal Research Reviews. 2001;21(1):83–101.
    1. Kardinal CG, Loprinzi CL, Schaid DJ, et al. A controlled trial of cyproheptadine in cancer patients with anorexia and/or cachexia. Cancer. 1990;65(12):2657–2662.
    1. Gordon JN, Trebble TM, Ellis RD, Duncan HD, Johns T, Goggin PM. Thalidomide in the treatment of cancer cachexia: a randomised placebo controlled trial. Gut. 2005;54(4):540–545.
    1. Moreira AL, Sampaio EP, Zmuidzinas A, Frindt P, Smith KA, Kaplan G. Thalidomide exerts its inhibitory action on tumor necrosis factor alpha by enhancing mRNA degradation. The Journal of Experimental Medicine. 1993;177(6):1675–1680.
    1. Gordon JN, Goggin PM. Thalidomide and its derivatives: emerging from the wilderness. Postgraduate Medical Journal. 2003;79(929):127–132.
    1. Goldberg RM, Loprinzi CL, Mailliard JA, et al. Pentoxifylline for treatment of cancer anorexia and cachexia? A randomized, double-blind, placebo-controlled trial. Journal of Clinical Oncology. 1995;13(11):2856–2859.
    1. Dewey A, Baughan C, Dean T, Higgins B, Johnson I. Eicosapentaenoic acid (EPA, an omega-3 fatty acid from fish oils) for the treatment of cancer cachexia. Cochrane Database of Systematic Reviews. 2007;(1) Article ID CD004597.
    1. Price SA, Tisdale MJ. Mechanism of inhibition of a tumor lipid-mobilizing factor by eicosapentaenoic acid. Cancer Research. 1998;58(21):4827–4831.
    1. Lissoni P, Paolorossi F, Ardizzoia A, et al. A randomized study of chemotherapy with cisplatin plus etoposide versus chemoendocrine therapy with cisplatin, etoposide and the pineal hormone melatonin as a first-line treatment of advanced non-small cell lung cancer patients in a poor clinical state. Journal of Pineal Research. 1997;23(1):15–19.
    1. Lissoni P. Is there a role for melatonin in supportive care? Supportive Care in Cancer. 2002;10(2):110–116.
    1. Kotler DP. Cachexia. Annals of Internal Medicine. 2000;133(8):622–634.
    1. Lundholm K, Daneryd P, Körner U, Hyltander A, Bosaeus I. Evidence that long-term COX-treatment improves energy homeostasis and body composition in cancer patients with progressive cachexia. International Journal of Oncology. 2004;24(3):505–512.
    1. Todorov P, Cariuk P, McDevitt T, Coles B, Fearon K, Tisdale M. Characterization of a cancer cachectic factor. Nature. 1996;379(6567):739–742.
    1. Hirai K, Hussey HJ, Barber MD, Price SA, Tisdale MJ. Biological evaluation of a lipid-mobilizing factor isolated from the urine of cancer patients. Cancer Research. 1998;58(11):2359–2365.
    1. Skipworth RJE, Stewart GD, Dejong CHC, Preston T, Fearon KCH. Pathophysiology of cancer cachexia: much more than host-tumour interaction? Clinical Nutrition. 2007;26(6):667–676.
    1. Watchorn TM, Waddell I, Dowidar N, Ross JA. Proteolysis-inducing factor regulates hepatic gene expression via the transcription factors NF-(kappa)B and STAT3. The FASEB Journal. 2001;15(3):562–564.
    1. Whitehouse AS, Tisdale MJ. Increased expression of the ubiquitin—proteasome pathway in murine myotubes by proteolysis-inducing factor (PIF) is associated with activation of the transcription factor NF-κB. British Journal of Cancer. 2003;89(6):1116–1122.
    1. Monitto CL, Dong SM, Jen J, Sidransky D. Characterization of a human homologue of proteolysis-inducing factor and its role in cancer cachexia. Clinical Cancer Research. 2004;10(17):5862–5869.
    1. Wieland BM, Stewart GD, Skipworth RJE, et al. Is there a human homologue to the murine proteolysis-inducing factor? Clinical Cancer Research. 2007;13(17):4984–4992.
    1. Deans C, Wigmore S, Paterson-Brown S, Black J, Ross J, Fearon KCH. Serum parathyroid hormone-related peptide is associated with systemic inflammation and adverse prognosis in gastroesophageal carcinoma. Cancer. 2005;103(9):1810–1818.
    1. Todorov PT, McDevitt TM, Meyer DJ, Ueyama H, Ohkubo I, Tisdale MJ. Purification and characterization of a tumor lipid-mobilizing factor. Cancer Research. 1998;58(11):2353–2358.
    1. Khan S, Tisdale MJ. Catabolism of adipose tissue by a tumour-produced lipid-mobilising factor. International Journal of Cancer. 1999;80(3):444–447.
    1. Islam-Ali B, Khan S, Price SA, Tisdale MJ. Modulation of adipocyte G-protein expression in cancer cachexia by a lipid-mobilizing factor (LMF) British Journal of Cancer. 2001;85(5):758–763.
    1. Gelin J, Moldawer LL, Lonnroth C, Sherry B, Chizzonite R, Lundholm K. Role of endogenous tumor necrosis factor α and interleukin 1 for experimental tumor growth and the development of cancer cachexia. Cancer Research. 1991;51(1):415–421.
    1. Strassmann G, Fong M, Kenney JS, Jacob CO. Evidence for the involvement of interleukin 6 in experimental cancer cachexia. Journal of Clinical Investigation. 1992;89(5):1681–1684.
    1. Yasumoto K, Mukaida N, Harada A, et al. Molecular analysis of the cytokine network involved in cachexia in colon 26 adenocarcinoma-bearing mice. Cancer Research. 1995;55(4):921–927.
    1. Matthys P, Heremans H, Opdenakker G, Billiau A. Anti-interferon-γ antibody treatment, growth of Lewis lung tumours in mice and tumour-associated cachexia. European Journal of Cancer. 1991;27(2):182–187.
    1. Deans DAC, Wigmore SJ, Gilmour H, Paterson-Brown S, Ross JA, Fearon KCH. Elevated tumour interleukin-1beta is associated with systemic inflammation: a marker of reduced survival in gastro-oesophageal cancer. British Journal of Cancer. 2006;95(11):1568–1575.
    1. O’Riordain MG, Falconer JS, Maingay J, Fearon KC, Ross JA. Peripheral blood cells from weight-losing cancer patients control the hepatic acute phase response by a primarily interleukin-6 dependent mechanism. International Journal of Oncology. 1999;15(4):823–827.
    1. Martignoni ME, Kunze P, Hildebrandt W, et al. Role of mononuclear cells and inflammatory cytokines in pancreatic cancer-related cachexia. Clinical Cancer Research. 2005;11(16):5802–5808.
    1. Gabay C, Kushner I. Acute-phase proteins and other systemic responses to inflammation. The New England Journal of Medicine. 1999;340(6):448–454.
    1. Falconer JS, Fearon KCH, Ross JA, et al. Acute-phase protein response and survival duration of patients with pancreatic cancer. Cancer. 1995;75(8):2077–2082.
    1. Falconer JS, Fearon KCH, Plester CE, Ross JA, Carter DC. Cytokines, the acute-phase response, and resting energy expenditure in cachectic patients with pancreatic cancer. Annals of Surgery. 1994;219(4):325–331.
    1. O’Gorman P, McMillan DC, McArdle CS. Prognostic factors in advanced gastrointestinal cancer patients with weight loss. Nutrition and Cancer. 2000;37(1):36–40.
    1. McMillan DC. An inflammation-based prognostic score and its role in the nutrition-based management of patients with cancer. Proceedings of the Nutrition Society. 2008;67(3):257–262.
    1. Marsik C, Kazemi-Shirazi L, Schickbauer T, et al. C-reactive protein and all-cause mortality in a large hospital-based cohort. Clinical Chemistry. 2008;54(2):343–349.
    1. Scott HR, McMillan DC, Brown DJF, Forrest LM, McArdle CS, Milroy R. A prospective study of the impact of weight loss and the systemic inflammatory response on quality of life in patients with inoperable non-small cell lung cancer. Lung Cancer. 2003;40(3):295–299.
    1. Deans DAC, Tan BH, Wigmore SJ, et al. The influence of systemic inflammation, dietary intake and stage of disease on rate of weight loss in patients with gastro-oesophageal cancer. British Journal of Cancer. 2009;100(1):63–69.
    1. Deans C, Wigmore SJ. Systemic inflammation, cachexia and prognosis in patients with cancer. Current Opinion in Clinical Nutrition and Metabolic Care. 2005;8(3):265–269.
    1. Reeds PJ, Fjeld CR, Jahoor F. Do the differences between the amino acid compositions of acute-phase and muscle proteins have a bearing on nitrogen loss in traumatic states? Journal of Nutrition. 1994;124(6):906–910.
    1. Feinstein R, Kanety H, Papa MZ, Lunenfeld B, Karasik A. Tumor necrosis factor-α suppresses insulin-induced tyrosine phosphorylation of insulin receptor and its substrates. Journal of Biological Chemistry. 1993;268(35):26055–26058.
    1. Orr R, Fiatarone Singh M. The anabolic androgenic steroid oxandrolone in the treatment of wasting and catabolic disorders: review of efficacy and safety. Drugs. 2004;64(7):725–750.
    1. Costelli P, Muscaritoli M, Bossola M, et al. IGF-1 is downregulated in experimental cancer cachexia. American Journal of Physiology. 2006;291(3):R674–R683.
    1. Ramos EJB, Suzuki S, Marks D, Inui A, Asakawa A, Meguid MM. Cancer anorexia-cachexia syndrome: cytokines and neuropeptides. Current Opinion in Clinical Nutrition and Metabolic Care. 2004;7(4):427–434.
    1. Inui A. Cancer anorexia-cachexia syndrome: are neuropeptides the key? Cancer Research. 1999;59(18):4493–4501.
    1. Chance WT, Balasubramaniam A, Thompson H, Mohapatra B, Ramo J, Fischer JE. Assessment of feeding response of tumor-bearing rats to hypothalamic injection and infusion of neuropeptide Y. Peptides. 1996;17(5):797–801.
    1. Markison S, Foster AC, Chen C, et al. The regulation of feeding and metabolic rate and the prevention of murine cancer cachexia with a small-molecule melanocortin-4 receptor antagonist. Endocrinology. 2005;146(6):2766–2773.
    1. Marks DL, Ling N, Cone RD. Role of the central melanocortin system in cachexia. Cancer Research. 2001;61(4):1432–1438.
    1. Farooqi IS, Keogh JM, Yeo GSH, Lank EJ, Cheetham T, O’Rahilly S. Clinical spectrum of obesity and mutations in the melanocortin 4 receptor gene. The New England Journal of Medicine. 2003;348(12):1085–1095.
    1. Ollmann MM, Wilson BD, Yang YK, et al. Antagonism of Central Melanocortin receptors in vitro and in vivo by agouti-related protein. Science. 1997;278(5335):135–138.
    1. Seeley RJ, Yagaloff KA, Fisher SL, et al. Melanocortin receptors in leptin effects. Nature. 1997;390(6658):p. 349.
    1. Whitaker KW, Reyes TM. Central blockade of melanocortin receptors attenuates the metabolic and locomotor responses to peripheral interleukin-1β administration. Neuropharmacology. 2008;54(3):509–520.
    1. Kamegai J, Tamura H, Shimizu T, Ish S, II, Sugihara H, Wakabayashi I. Chronic central infusion of ghrelin increases hypothalamic neuropeptide Y and agouti-related protein mRNA levels and body weight in rats. Diabetes. 2001;50(7–12):2438–2443.
    1. Buccheri G, Ferrigno D. Importance of weight loss definition in the prognostic evaluation of non-small-cell lung cancer. Lung Cancer. 2001;34(3):433–440.
    1. Hess LM, Barakat R, Tian C, Ozols RF, Alberts DS. Weight change during chemotherapy as a potential prognostic factor for stage III epithelial ovarian carcinoma: a Gynecologic Oncology Group study. Gynecologic Oncology. 2007;107(2):260–265.
    1. Bachmann J, Heiligensetzer M, Krakowski-Roosen H, Friess H, Martignoni ME. Cachexia worsens prognosis in patients with resectable pancreatic cancer. Journal of Gastrointestinal Surgery. 2008;12(7):1193–1201.
    1. Andreyev HJN, Norman AR, Oates J, Cunningham D. Why do patients with weight loss have a worse outcome when undergoing chemotherapy for gastrointestinal malignancies? European Journal of Cancer. 1998;34(4):503–509.
    1. Ravasco P, Monteiro-Grillo I, Marques Vidal P, Camilo ME. Cancer: disease and nutrition are key determinants of patients’ quality of life. Supportive Care in Cancer. 2004;12(4):246–252.
    1. Persson C, Glimelius B. The relevance of weight loss for survival and quality of life in patients with advanced gastrointestinal cancer treated with palliative chemotherapy. Anticancer Research. 2002;22(6):3661–3668.
    1. Dahele M, Fearon KCH. Research methodology: cancer cachexia syndrome. Palliative Medicine. 2004;18(5):409–417.
    1. Moses AWG, Slater C, Preston T, Barber MD, Fearon KCH. Reduced total energy expenditure and physical activity in cachectic patients with pancreatic cancer can be modulated by an energy and protein dense oral supplement enriched with n-3 fatty acids. British Journal of Cancer. 2004;90(5):996–1002.
    1. Dahele M, Skipworth RJE, Wall L, Voss A, Preston T, Fearon KCH. Objective physical activity and self-reported quality of life in patients receiving palliative chemotherapy. Journal of Pain and Symptom Management. 2007;33(6):676–685.
    1. Biolo G, Ciocchi B, Stulle M, et al. Metabolic consequences of physical inactivity. Journal of Renal Nutrition. 2005;15(1):49–53.
    1. Fouladiun M, Körner U, Gunnebo L, Sixt-Ammilon P, Bosaeus I, Lundholm K. Daily physical-rest activities in relation to nutritional state, metabolism, and quality of life in cancer patients with progressive cachexia. Clinical Cancer Research. 2007;13(21):6379–6385.
    1. Bozzetti F. Basics in clinical nutrition: nutritional support in cancer. e-SPEN. 2010;5(3):e148–e152.
    1. Bozzetti F, Gavazzi C, Mariani L, Crippa F. Artificial nutrition in cancer patients: which route, what composition? World Journal of Surgery. 1999;23(6):577–583.
    1. Bruera E, Strasser F, Palmer JL, et al. Effect of fish oil on appetite and other symptoms in patients with advanced cancer and anorexia/cachexia: a double-blind, placebo-controlled study. Journal of Clinical Oncology. 2003;21(1):129–134.
    1. Berk L, James J, Schwartz A, et al. A randomized, double-blind, placebo-controlled trial of a β-hydroxyl β-methyl butyrate, glutamine, and arginine mixture for the treatment of cancer cachexia (RTOG 0122) Supportive Care in Cancer. 2008;16(10):1179–1188.
    1. Buccheri G, Ferrigno D. Importance of weight loss definition in the prognostic evaluation of non-small-cell lung cancer. Lung Cancer. 2001;34(3):433–440.
    1. Tchekmedyian NS, Zahyna D, Halpert C, Heber D. Clinical aspects of nutrition in advanced cancer. Oncology. 1992;49(supplement 2):3–7.
    1. Muscaritoli M, Costelli P, Aversa Z, Bonetto A, Baccino FM, Fanelli FR. New strategies to overcome cancer cachexia: from molecular mechanisms to the ’Parallel Pathway’. Asia Pacific Journal of Clinical Nutrition. 2008;17(supplement 1):387–390.
    1. Ravasco P, Monteiro-Grillo I, Vidal PM, Camilo ME. Dietary counseling improves patient outcomes: a prospective, randomized, controlled trial in colorectal cancer patients undergoing radiotherapy. Journal of Clinical Oncology. 2005;23(7):1431–1438.
    1. Ravasco P, Monteiro-Grillo I, Vidal PM, Camilo ME. Impact of nutrition on outcome: a prospective randomized controlled trial in patients with head and neck cancer undergoing radiotherapy. Head and Neck. 2005;27(8):659–668.
    1. Hutton JL, Martin L, Field CJ, et al. Dietary patterns in patients with advanced cancer: implications for anorexia-cachexia therapy. American Journal of Clinical Nutrition. 2006;84(5):1163–1170.
    1. Arends J, Bodoky G, Bozzetti F, et al. ESPEN guidelines on enteral nutrition: non-surgical oncology. Clinical Nutrition. 2006;25(2):245–259.
    1. Evans WK, Makuch R, Clamon GH. Limited impact of total parenteral nutrition on nutritional status during treatment for small cell lung cancer. Cancer Research. 1985;45(7):3347–3353.
    1. Elia M, Van Bokhorst-de van der Schueren MA, Garvey J, et al. Enteral (oral or tube administration) nutritional support and eicosapentaenoic acid in patients with cancer: a systematic review. International Journal of Oncology. 2006;28(1):5–23.
    1. Koretz RL, Lipman TO, Klein S. AGA technical review on parenteral nutrition. Gastroenterology. 2001;121(4):970–1001.
    1. Fritsche K. Fatty acids as modulators of the immune response. Annual Review of Nutrition. 2006;26(1):45–73.
    1. Barber MD, Ross JA, Voss AC, Tisdale MJ, Fearon KCH. The effect of an oral nutritional supplement enriched with fish oil on weight-loss in patients with pancreatic cancer. British Journal of Cancer. 1999;81(1):80–86.
    1. Wigmore SJ, Barber MD, Ross JA, Tisdale MJ, Fearon KCH. Effect of oral Eicosapentaenoic acid on weight loss in patients with pancreatic cancer. Nutrition and Cancer. 2000;36(2):177–184.
    1. Guarcello M, Riso S, Buosi R, D’Andrea F. EPA-enriched oral nutritional support in patients with lung cancer: effects on nutritional status and quality of life. Nutritional Therapy and Metabolism. 2007;24:168–175.
    1. Read JA, Beale PJ, Volker DH, Smith N, Childs A, Clarke SJ. Nutrition intervention using an eicosapentaenoic acid (EPA)-containing supplement in patients with advanced colorectal cancer. Effects on nutritional and inflammatory status: a phase II trial. Supportive Care in Cancer. 2007;15(3):301–307.
    1. Fearon KCH, Von Meyenfeldt MF, Moses AGW, et al. Effect of a protein and energy dense n-3 fatty acid enriched oral supplement on loss of weight and lean tissue in cancer cachexia: a randomised double blind trial. Gut. 2003;52(10):1479–1486.
    1. Jatoi A, Rowland K, Loprinzi CL, et al. An eicosapentaenoic acid supplement versus megestrol acetate versus both for patients with cancer-associated wasting: a North Central Cancer Treatment Group and National Cancer Institute of Canada collaborative effort. Journal of Clinical Oncology. 2004;22(12):2469–2476.
    1. López AP, Roqué I Figuls M, Cuchi GU, et al. Systematic review of megestrol acetate in the treatment of anorexia-cachexia syndrome. Journal of Pain and Symptom Management. 2004;27(4):360–369.
    1. Gridelli C, Gallo C, Ceribelli A, et al. Factorial phase III randomised trial of rofecoxib and prolonged constant infusion of gemcitabine in advanced non-small-cell lung cancer: the GEmcitabine-COxib in NSCLC (GECO) study. Lancet Oncology. 2007;8(6):500–512.
    1. Hussey HJ, Tisdale MJ. Effect of the specific cyclooxygenase-2 inhibitor meloxicam on tumour growth and cachexia in a murine model. International Journal of Cancer. 2000;87(1):95–100.
    1. Hyltander A, Daneryd P, Sandström R, Körner U, Lundholm K. β-adrenoceptor activity and resting energy metabolism in weight losing cancer patients. European Journal of Cancer. 2000;36(3):330–334.
    1. Ryall JG, Lynch GS. The potential and the pitfalls of β-adrenoceptor agonists for the management of skeletal muscle wasting. Pharmacology and Therapeutics. 2008;120(3):219–232.
    1. Herndon DN, Hart DW, Wolf SE, Chinkes DL, Wolfe RR. Reversal of catabolism by beta-blockade after severe burns. The New England Journal of Medicine. 2001;345(17):1223–1229.
    1. Jatoi A, Dakhil SR, Nguyen PL, et al. A placebo-controlled double blind trial of etanercept for the cancer anorexia/weight loss syndrome: results from NOOC1 from the North Central Cancer Treatment Group. Cancer. 2007;110(6):1396–1403.
    1. Jatoi A, Ritter HL, Dueck A, et al. A placebo-controlled, double-blind trial of infliximab for cancer-associated weight loss in elderly and/or poor performance non-small cell lung cancer patients (N01C9) Lung Cancer. 2010;68(2):234–239.
    1. Loprinzi CL, Kugler JW, Sloan JA, et al. Randomized comparison of megestrol acetate versus dexamethasone versus fluoxymesterone for the treatment of cancer anorexia/cachexia. Journal of Clinical Oncology. 1999;17(10):3299–3306.
    1. Mantovani G, Maccio A, Madeddu C, et al. Randomized phase III clinical trial of five different arms of treatment in 332 patients with cancer cachexia. Oncologist. 2010;15(2):200–211.
    1. DeBoer MD. Update on melanocortin interventions for cachexia: progress toward clinical application. Nutrition. 2010;26(2):146–151.
    1. Nakazato M, Murakami N, Date Y, et al. A role for ghrelin in the central regulation of feeding. Nature. 2001;409(6817):194–198.
    1. DeBoer MD, Xin XZ, Levasseur P, et al. Ghrelin treatment causes increased food intake and retention of lean body mass in a rat model of cancer cachexia. Endocrinology. 2007;148(6):3004–3012.
    1. Kung T, Springer J, Doehner W, Anker SD, Von Haehling S. Novel treatment approaches to cachexia and sarcopenia: highlights from the 5th Cachexia Conference. Expert Opinion on Investigational Drugs. 2010;19(4):579–585.
    1. Zimmers TA, Davies MV, Koniaris LG, et al. Induction of cachexia in mice by systemically administered myostatin. Science. 2002;296(5572):1486–1488.

Source: PubMed

3
Iratkozz fel