Journal of the American College of Surgeons
Volume 197, Issue 1 , Pages 143-161 , July 2003

Understanding and managing cancer cachexia

  • Neil MacDonald, MD, FRCP

      Affiliations

    • Department of Oncology (MacDonald), McGill University, Gerald Bronfman Centre for Clinical Research in Oncology, Montreal, Quebec, Canada
  • ,
  • Alexandra M Easson, MD, FRCSC, FACS

      Affiliations

    • Department of Surgical Oncology (Easson), University of Toronto, Princess Margaret Hospital, University Health Network, Toronto, Ontario, Canada
  • ,
  • Vera C Mazurak, PhD

      Affiliations

    • Department of Agriculture (Mazurak, Baracos), Food and Nutritional Science,, Edmonton, Alberta, Canada
  • ,
  • Geoffrey P Dunn, MD, FACS

      Affiliations

    • Department of Surgery (Dunn), Hamot Medical Center, Erie, PA, USA
  • ,
  • Vickie E Baracos, PhD

      Affiliations

    • Department of Agriculture (Mazurak, Baracos), Food and Nutritional Science,, Edmonton, Alberta, Canada
    • Department of Oncology (Baracos), University of Alberta, Edmonton, Alberta, Canada
    • Corresponding Author InformationCorrespondence address: Vickie E Baracos, PhD, Department of Oncology & Department of Agriculture, Food and Nutritional Science, University of Alberta, 2-06H Agriculture Forestry Center, Edmonton, Alberta, Canada T6G 2P5.

Received 2 April 2003 ,Accepted 3 April 2003.

References 

  1. Easson AM, Hinshaw DB, Johnson DL. The role of tube feeding and total parenteral nutrition in advanced illness. J Am Coll Surg. 2002;194:225–228
  2. Vigano A, Bruera E, Jhangri GS, et al.  Clinical survival predictors in patients with advanced cancer. Arch Intern Med. 2000;160:861–868
  3. Baracos VE. Hypercatabolism and hypermetabolism in wasting states. Curr Opin Clin Nutr Metab Care. 2002;5:237–239
  4. Baracos VE. Regulation of skeletal-muscle-protein turnover in cancer-associated cachexia. Nutrition. 2000;16:1015–1018
  5. Costelli P, Baccino FM. Cancer cachexia (from experimental models to patient management). Curr Opin Clin Nutr Metab Care. 2000;3:177–181
  6. Argiles JM, Lopez-Soriano FJ. The role of cytokines in cancer cachexia. Med Res Rev. 1999;19:223–248
  7. Baracos VE. Management of muscle wasting in cancer-associated cachexia (understanding gained from experimental studies). Cancer. 2001;92(6 Suppl):1669–1677
  8. Basaria S, Wahlstrom JT, Dobs AS. Clinical review 138 (Anabolic-androgenic steroid therapy in the treatment of chronic diseases). J Clin Endocrinol Metab. 2001;86:5108–5117
  9. Tisdale MJ. Cachexia in cancer patients. Nat Rev Cancer. 2002;2:862–871
  10. Argiles JM, Alvarez B, Carbo N, et al.  The divergent effects of tumour necrosis factor-alpha on skeletal muscle (implications in wasting). Eur Cytokine Netw. 2000;11:552–559
  11. Barber MD, Powell JJ, Lynch SF, et al.  A polymorphism of the interleukin-1 beta gene influences survival in pancreatic cancer. Br J Cancer. 2000;83:1443–1447
  12. Kotler DP. Cachexia. Ann Intern Med. 2000;133:622–634
  13. Wigmore SJ, MacMahon AJ, Sturgeon CM, Fearon KC. Acute-phase protein response, survival and tumour recurrence in patients with colorectal cancer. Br J Surg. 2001;88:255–260
  14. Fischer CP, Bode BP, Souba WW. A sarcoma-derived protein regulates hepatocyte metabolism via autocrine production of tumor necrosis factor-alpha. Ann Surg. 1996;224:476–483
  15. Costelli P, Llovera M, Carbo N, et al.  Interleukin-1 receptor antagonist (IL-1ra) is unable to reverse cachexia in rats bearing an ascites hepatoma (Yoshida AH-130). Cancer Lett. 1995;95:33–38
  16. Costelli P, Carbo N, Tessitore L, et al.  Tumor necrosis factor-alpha mediates changes in tissue protein turnover in a rat cancer cachexia model. J Clin Invest. 1993;92:2783–2789
  17. Llovera M, Garcia-Martinez C, Lopez-Soriano J, et al.  Role of TNF receptor 1 in protein turnover during cancer cachexia using gene knockout mice. Mol Cell Endocrinol. 1998;142:183–189
  18. Fujita J, Tsujinaka T, Yano M, et al.  Anti-interleukin-6 receptor antibody prevents muscle atrophy in colon-26 adenocarcinoma-bearing mice with modulation of lysosomal and ATP-ubiquitin-dependent proteolytic pathways. Int J Cancer. 1996;68:637–643
  19. Marette A. Mediators of cytokine-induced insulin resistance in obesity and other inflammatory settings. Curr Opin Clin Nutr Metab Care. 2002;5:377–383
  20. Ross JA, Fearon KC. Eicosanoid-dependent cancer cachexia and wasting. Curr Opin Clin Nutr Metab Care. 2002;5:241–248
  21. Badawi AF, Badr MZ. Expression of cyclooxygenase-2 and peroxisome proliferator-activated receptor-gamma and levels of prostaglandin E2 and 15-deoxy-delta12, 14-prostaglandin J2 in human breast cancer and metastasis. Int J Cancer. 2003;103:84–90
  22. Zweifel BS, Davis TW, Ornberg RL, Masferrer JL. Direct evidence for a role of cyclooxygenase 2-derived prostaglandin E2 in human head and neck xenograft tumors. Cancer Res. 2002;62:6706–6711
  23. Cahlin C, Gelin J, Delbro D, et al.  Effect of cyclooxygenase and nitric oxide synthase inhibitors on tumor growth in mouse tumor models with and without cancer cachexia related to prostanoids. Cancer Res. 2000;60:1742–1749
  24. Calder PC. Dietary modification of inflammation with lipids. Proc Nutr Soc. 2002;61:345–358
  25. Tisdale MJ. ‘The cancer cachectic factor. Support Care Cancer. 2003;11:73–78
  26. Lorite MJ, Smith HJ, Arnold JA, et al.  Activation of ATP-ubiquitin-dependent proteolysis in skeletal muscle in vivo and murine myoblasts in vitro by a proteolysis-inducing factor (PIF). Br J Cancer. 2001;85:297–302
  27. Mikasa K, Sawaki M, Kita E, et al.  Significant survival benefit to patients with advanced non-small-cell lung cancer from treatment with clarithromycin. Chemotherapy. 1997;43:288–296
  28. Ianaro A, Ialenti A, Maffia P, et al.  Anti-inflammatory activity of macrolide antibiotics. J Pharmacol Exp Ther. 2000;292:156–163
  29. Sakamoto M, Mikasa K, Majima T, et al.  Anti-cachectic effect of clarithromycin for patients with unresectable non-small cell lung cancer. Chemotherapy. 2001;47:444–451
  30. Bruera E, Neumann CM, Pituskin E, et al.  Thalidomide in patients with cachexia due to terminal cancer (preliminary report). Ann Oncol. 1999;10:857–859
  31. Zhou S, Kestell P, Tingle MD, Paxton JW. Thalidomide in cancer treatment (a potential role in the elderly?). Drugs Aging. 2002;19:85–100
  32. Lorite MJ, Cariuk P, Tisdale MJ. Induction of muscle protein degradation by a tumour factor. Br J Cancer. 1997;76:1035–1040
  33. Cariuk P, Lorite MJ, Todorov PT, et al.  Induction of cachexia in mice by a product isolated from the urine of cachectic cancer patients. Br J Cancer. 1997;76:606–613
  34. Lorite MJ, Thompson MG, Drake JL, et al.  Mechanism of muscle protein degradation induced by a cancer cachectic factor. Br J Cancer. 1998;78:850–856
  35. Todorov PT, Field WN, Tisdale MJ. Role of a proteolysis-inducing factor (PIF) in cachexia induced by a human melanoma (G361). Br J Cancer. 1999;80:1734–1737
  36. Cabal-Manzano R, Bhargava P, Torres-Duarte A, et al.  Proteolysis-inducing factor is expressed in tumours of patients with gastrointestinal cancers and correlates with weight loss. Br J Cancer. 2001;84:1599–1601
  37. Wigmore SJ, Todorov PT, Barber MD, et al.  Characteristics of patients with pancreatic cancer expressing a novel cancer cachectic factor. Br J Surg. 2000;87:53–58
  38. Simons JP, Schols AM, Buurman WA, Wouters EF. Weight loss and low body cell mass in males with lung cancer (relationship with systemic inflammation, acute-phase response, resting energy expenditure, and catabolic and anabolic hormones). Clin Sci (Lond). 1999;97:215–223
  39. Jagoe RT, Goldberg AL. What do we really know about the ubiquitin-proteasome pathway in muscle atrophy?. Curr Opin Clin Nutr Metab Care. 2001;4:183–190
  40. Glickman MH, Ciechanover A. The ubiquitin-proteasome proteolytic pathway (destruction for the sake of construction). Physiol Rev. 2002;82:373–428
  41. Bossola M, Muscaritoli M, Costelli P, et al.  Increased muscle ubiquitin mRNA levels in gastric cancer patients. Am J Physiol Regul Integr Comp Physiol. 2001;280:R1518–R1523
  42. Bossola M, Muscaritoli M, Costelli P, et al.  Increased muscle proteasome activity correlates with disease severity in gastric cancer patients. Ann Surg. 2003;237:384–389
  43. 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:E996–1006
  44. Bodine SC, Latres E, Baumhueter S, et al.  Identification of ubiquitin ligases required for skeletal muscle atrophy. Science. 2001;294:1704–1708
  45. Holmes-McNary M. Nuclear factor kappa B signaling in catabolic disorders. Curr Opin Clin Nutr Metab Care. 2002;5:255–263
  46. Baldwin AS. Control of oncogenesis and cancer therapy resistance by the transcription factor NF-kappaB. J Clin Invest. 2001;107:241–246
  47. Watchorn TM, Waddell I, Dowidar N, Ross JA. Proteolysis-inducing factor regulates hepatic gene expression via the transcription factors NF-(kappa)B and STAT3. FASEB J. 2001;15:562–564
  48. Ferrando AA, Stuart CA, Sheffield-Moore M, Wolfe RR. Inactivity amplifies the catabolic response of skeletal muscle to cortisol. J Clin Endocrinol Metab. 1999;84:3515–3521
  49. Ferrando AA, Sheffield-Moore M, Paddon-Jones D, et al.  Differential anabolic effects of testosterone and amino acid feeding in older men. J Clin Endocrinol Metab. 2003;88:358–362
  50. Mackenzie M, Baracos VE. Cancer-associated cachexia: altered metabolism of protein and amino acids. In: Cynober L, ed. Amino acid metabolism and therapy in health and diseases. Palm Springs, FL: CRC Press; 2003 (in press)
  51. Kaibara A, Yoshida S, Yamasaki K, et al.  Effect of glutamine and chemotherapy on protein metabolism in tumor-bearing rats. J Surg Res. 1994;57:143–149
  52. Austgen TR, Dudrick PS, Sitren H, et al.  The effects of glutamine-enriched total parenteral nutrition on tumor growth and host tissues. Ann Surg. 1992;215:107–113
  53. Yoshida S, Kaibara A, Yamasaki K, et al.  Effect of glutamine supplementation on protein metabolism and glutathione in tumor-bearing rats. JPEN J Parenter Enteral Nutr. 1995;19:492–497
  54. Le Bricon T, Cynober L, Field CJ, Baracos VE. Supplemental nutrition with ornithine alpha-ketoglutarate in rats with cancer-associated cachexia (surgical treatment of the tumor improves efficacy of nutritional support). J Nutr. 1995;125:2999–3010
  55. 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?. J Nutr. 1994;124:906–910
  56. Anthony JC, Yoshizawa F, Anthony TG, et al.  Leucine stimulates translation initiation in skeletal muscle of postabsorptive rats via a rapamycin-sensitive pathway. J Nutr. 2000;130:2413–2419
  57. Maltoni M, Nanni O, Scarpi E, et al.  High-dose progestins for the treatment of cancer anorexia-cachexia syndrome (a systematic review of randomized clinical trials). Ann Oncol. 2001;12:289–300
  58. Mantovani G, Maccio A, Lai P, et al.  Cytokine activity in cancer-related anorexia/cachexia (role of megestrol acetate and medroxyprogesterone acetate). Semin Oncol. 1998;25(2 Suppl 6):45–52
  59. McCarthy HD, Crowder RE, Dryden S, Williams G. Megestrol acetate stimulates food and water intake in the rat (effects on regional hypothalamic neuropeptide Y concentrations). Eur J Pharmacol. 1994;265:99–102
  60. Jatoi A, Kumar S, Sloan JA, Nguyen PL. On appetite and its loss. J Clin Oncol. 2000;18:2930–2932
  61. Lambert CP, Sullivan DH, Freeling SA, et al.  Effects of testosterone replacement and/or resistance exercise on the composition of megestrol acetate stimulated weight gain in elderly men (a randomized controlled trial). J Clin Endocrinol Metab. 2002;87:2100–2106
  62. Loprinzi CL, Schaid DJ, Dose AM, et al.  Body-composition changes in patients who gain weight while receiving megestrol acetate. J Clin Oncol. 1993;11:152–154
  63. Rowland KM, Loprinzi CL, Shaw EG, et al.  Randomized double-blind placebo-controlled trial of cisplatin and etoposide plus megestrol acetate/placebo in extensive-stage small-cell lung cancer (a North Central Cancer Treatment Group study). J Clin Oncol. 1996;14:135–141
  64. Macbeth FR, Gregor A, Cottier B. Randomized study of megestrol acetate and prednisolone for anorexia and weight loss in patients with lung cancer. World Conference on Lung Cancer Abstract 334; 1994
  65. Ridker PM, Rifai N, Clearfield M, et al.  Measurement of C-reactive protein for the targeting of statin therapy in the primary prevention of acute coronary events. N Engl J Med. 2001;344:1959–1965
  66. Albert MA, Danielson E, Rifai N, Ridker PM. Effect of statin therapy on C-reactive protein levels (a randomized trial and cohort study). JAMA. 2001;286:64–70
  67. Scott HR, McMillan DC, Forrest LM, et al.  The systemic inflammatory response, weight loss, performance status and survival in patients with inoperable non-small cell lung cancer. Br J Cancer. 2002;87:264–267
  68. Falconer JS, Fearon KC, Ross JA, et al.  Acute-phase protein response and survival duration of patients with pancreatic cancer. Cancer. 1995;75:2077–2082
  69. 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;11:60–62
  70. Boehm M, Nabel EG. Angiotensin-converting enzyme 2—a new cardiac regulator. N Engl J Med. 2002;347:1795–1797
  71. Mann DL. Inflammatory mediators and the failing heart (past, present, and the foreseeable future). Circ Res. 2002;91:988–998
  72. Onder G, Penninx BW, Balkrishnan R, et al.  Relation between use of angiotensin-converting enzyme inhibitors and muscle strength and physical function in older women (an observational study). Lancet. 2002;359:926–930
  73. Montgomery H, Clarkson P, Barnard M, et al.  Angiotensin-converting-enzyme gene insertion/deletion polymorphism and response to physical training. Lancet. 1999;353:541–545
  74. Yoshiji H, Kuriyama S, Kawata M, et al.  The angiotensin-I-converting enzyme inhibitor perindopril suppresses tumor growth and angiogenesis (possible role of the vascular endothelial growth factor). Clin Cancer Res. 2001;7:1073–1078
  75. Lindholm LH, Anderson H, Ekbom T, et al.  Relation between drug treatment and cancer in hypertensives in the Swedish Trial in Old Patients with Hypertension 2 (a 5-year, prospective, randomised, controlled trial). Lancet. 2001;358:539–544
  76. Meier CR, Derby LE, Jick SS, Jick H. Angiotensin-converting enzyme inhibitors, calcium channel blockers, and breast cancer. Arch Intern Med. 2000;160:349–353
  77. Takizawa H, Desaki M, Ohtoshi T, et al.  Erythromycin suppresses interleukin 6 expression by human bronchial epithelial cells (a potential mechanism of its anti-inflammatory action). Biochem Biophys Res Commun. 1995;210:781–786
  78. Morikawa K, Watabe H, Araake M, Morikawa S. Modulatory effect of antibiotics on cytokine production by human monocytes in vitro. Antimicrob Agents Chemother. 1996;40:1366–1370
  79. Yanagihara K, Tomono K, Kuroki M, et al.  Intrapulmonary concentrations of inflammatory cytokines in a mouse model of chronic respiratory infection caused by Pseudomonas aeruginosa. Clin Exp Immunol. 2000;122:67–71
  80. Sassa K, Mizushima Y, Fujishita T, et al.  Therapeutic effect of clarithromycin on a transplanted tumor in rats. Antimicrob Agents Chemother. 1999;43:67–72
  81. Hamada K, Mikasa K, Yunou Y, et al.  Adjuvant effect of clarithromycin on chemotherapy for murine lung cancer. Chemotherapy. 2000;46:49–61
  82. Yatsunami J, Fukuno Y, Nagata M, et al.  Roxithromycin and clarithromycin, 14-membered ring macrolides, potentiate the antitumor activity of cytotoxic agents against mouse B16 melanoma cells. Cancer Lett. 1999;147:17–24
  83. Huso ME, Hampl JS, Johnston CS, Swan PD. Creatine supplementation influences substrate utilization at rest. J Appl Physiol. 2002;93:2018–2022
  84. Kreider RB, Ferreira M, Wilson M, et al.  Effects of creatine supplementation on body composition, strength, and sprint performance. Med Sci Sports Exerc. 1998;30:73–82
  85. Volek JS, Duncan ND, Mazzetti SA, et al.  Performance and muscle fiber adaptations to creatine supplementation and heavy resistance training. Med Sci Sports Exerc. 1999;31:1147–1156
  86. Juhn MS, Tarnopolsky M. Oral creatine supplementation and athletic performance (a critical review). Clin J Sport Med. 1998;8:286–297
  87. Izquierdo M, Ibanez J, Gonzalez-Badillo JJ, Gorostiaga EM. Effects of creatine supplementation on muscle power, endurance, and sprint performance. Med Sci Sports Exerc. 2002;34:332–343
  88. Gotshalk LA, Volek JS, Staron RS, et al.  Creatine supplementation improves muscular performance in older men. Med Sci Sports Exerc. 2002;34:537–543
  89. Agteresch HJ, Rietveld T, Kerkhofs LG, et al.  Beneficial effects of adenosine triphosphate on nutritional status in advanced lung cancer patients (a randomized clinical trial). J Clin Oncol. 2002;20:371–378
  90. Juhn MS, Tarnopolsky M. Potential side effects of oral creatine supplementation (a critical review). Clin J Sport Med. 1998;8:298–304
  91. Langer CJ, Hoffman JP, Ottery FD. Clinical significance of weight loss in cancer patients (rationale for the use of anabolic agents in the treatment of cancer-related cachexia). Nutrition. 2001;17(1 Suppl):S1–20
  92. Ferrando AA, Sheffield-Moore M, Yeckel CW, et al.  Testosterone administration to older men improves muscle function (molecular and physiological mechanisms). Am J Physiol Endocrinol Metab. 2002;282:E601–E607
  93. Spratt DI. Altered gonadal steroidogenesis in critical illness (is treatment with anabolic steroids indicated?). Best Pract Res Clin Endocrinol Metab. 2001;15:479–494
  94. Von Roenn J, Tchekmedyian S, Ottery FD. Oxandrolone increases weight, lean tissue, performance status and quality of life scores in cancer related weight loss. Support Care Cancer Abstract 2002
  95. Padero MC, Bhasin S, Friedman TC. Androgen supplementation in older women (too much hype, not enough data). J Am Geriatr Soc. 2002;50:1131–1140
  96. Taggart DP, Gray CE, Bowman A, et al.  Serum androgens and gonadotrophins in bronchial carcinoma. Respir Med. 1993;87:455–460
  97. Chlebowski RT, Palomares MR, Lillington L, Grosvenor M. Recent implications of weight loss in lung cancer management. Nutrition. 1996;12(1 Suppl):S43–S47
  98. Sheffield-Moore M, Urban RJ, Wolf SE, et al.  Short-term oxandrolone administration stimulates net muscle protein synthesis in young men. J Clin Endocrinol Metab. 1999;84:2705–2711
  99. Wolfe R, Ferrando A, Sheffield-Moore M, Urban R. Testosterone and muscle protein metabolism. Mayo Clin Proc. 2000;75(Suppl):S55–S59
  100. Amory JK, Chansky HA, Chansky KL, et al.  Preoperative supraphysiological testosterone in older men undergoing knee replacement surgery. J Am Geriatr Soc. 2002;50:1698–1701
  101. Bhasin S, Storer TW, Javanbakht M, et al.  Testosterone replacement and resistance exercise in HIV-infected men with weight loss and low testosterone levels. JAMA. 2000;283:763–770
  102. Fairfield WP, Treat M, Rosenthal DI, et al.  Effects of testosterone and exercise on muscle leanness in eugonadal men with AIDS wasting. J Appl Physiol. 2001;90:2166–2171
  103. Kong A, Edmonds P. Testosterone therapy in HIV wasting syndrome (systematic review and meta-analysis). Lancet Infect Dis. 2002;2:692–699
  104. Mulligan K, Schambelan M. Anabolic treatment with GH, IGF-I, or anabolic steroids in patients with HIV-associated wasting. Int J Cardiol. 2002;85:151–159
  105. Loprinzi CL, Kugler JW, Sloan JA, et al.  Randomized comparison of megestrol acetate versus dexamethasone versus fluoxymesterone for the treatment of cancer anorexia/cachexia. J Clin Oncol. 1999;17:3299–3306
  106. Bishop JF, Smith JG, Jeal PN, et al.  The effect of danazol on tumour control and weight loss in patients on tamoxifen therapy for advanced breast cancer (a randomised double-blind placebo controlled trial). Eur J Cancer. 1993;29A:814–818
  107. Chlebowski RT, Herrold J, Ali I. Influence of nandrolone decanoate on weight loss in advanced non-small cell lung cancer. Cancer. 1986;58:183–186
  108. Hack V, Breitkreutz R, Kinscherf R, et al.  The redox state as a correlate of senescence and wasting and as a target for therapeutic intervention. Blood. 1998;92:59–67
  109. May PE, Barber A, D’Olimpio JT, et al.  Reversal of cancer-related wasting using oral supplementation with a combination of beta-hydroxy-beta-methylbutyrate, arginine, and glutamine. Am J Surg. 2002;183:471–479
  110. Jones PJH, Kubow S. Lipids, sterols, and their metabolites. In: Shils ME, Olson JA, Shike M, Ross AC, eds. Modern nutrition in health and disease. Baltimore, MD: Williams & Wilkins; 1998:85
  111. Clandinin JJ, Jumpsen J, Suh M. Relationship between fatty acid accretion, membrane composition, and biologic functions. J Pediatr 1994;125:S25–S32
  112. Calder PC. More good news about fish oil. Nutrition. 2001;17:158–160
  113. Lee TH, Hoover RL, Williams JD, et al.  Effect of dietary enrichment with eicosapentaenoic and docosahexaenoic acids on in vitro neutrophil and monocyte leukotriene generation and neutrophil function. N Engl J Med. 1985;312:1217–1224
  114. Barber MD, Ross JA, Preston T, et al.  Fish oil-enriched nutritional supplement attenuates progression of the acute-phase response in weight-losing patients with advanced pancreatic cancer. J Nutr. 1999;129:1120–1125
  115. Hardman WE, Moyer MP, Cameron IL. Consumption of an omega-3 fatty acids product, INCELL AAFA, reduced side-effects of CPT-11 (irinotecan) in mice. Br J Cancer. 2002;86:983–988
  116. Hardman WE, Moyer MP, Cameron IL. Fish oil supplementation enhanced CPT-11 (irinotecan) efficacy against MCF7 breast carcinoma xenografts and ameliorated intestinal side-effects. Br J Cancer. 1999;81:440–448
  117. Burns CP, Halabi S, Clamon GH, et al.  Phase I clinical study of fish oil fatty acid capsules for patients with cancer cachexia (cancer and leukemia group B study 9473). Clin Cancer Res. 1999;5:3942–3947
  118. Wigmore SJ, Barber MD, Ross JA, et al.  Effect of oral eicosapentaenoic acid on weight loss in patients with pancreatic cancer. Nutr Cancer. 2000;36:177–184
  119. Gogos CA, Ginopoulos P, Salsa B, et al.  Dietary omega-3 polyunsaturated fatty acids plus vitamin E restore immunodeficiency and prolong survival for severely ill patients with generalized malignancy (a randomized control trial). Cancer. 1998;82:395–402
  120. 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). J Clin Oncol. 2003;21:129–134
  121. Pratt VC, Watanabe S, Bruera E, et al.  Plasma and neutrophil fatty acid composition in advanced cancer patients and response to fish oil supplementation. Br J Cancer. 2002;87:1370–1378
  122. Barber MD, Fearon KC, Tisdale MJ, et al.  Effect of a fish oil-enriched nutritional supplement on metabolic mediators in patients with pancreatic cancer cachexia. Nutr Cancer. 2001;40:118–124
  123. Jatoi A, Rowland KM Jr, Loprinzi CL, et al. A phase III, double blind, placebo-controlled randomized comparison of megestrol acetate (megace) versus an omega-3 fatty acid (EPA)-enriched nutritional supplement versus both. Abstract # American Society of Clinical Oncology, 2003
  124. McCann RM, Hall WJ, Groth-Juncker A. Comfort care for terminally ill patients. The appropriate use of nutrition and hydration. JAMA. 1994;272:1263–1266
  125. Bruera E, Kuehn N, Miller MJ, et al.  The Edmonton Symptom Assessment System (ESAS) (a simple method for the assessment of palliative care patients). J Palliat Care. 1991;7:6–9
  126. European Organization for Research and Treatment of Cancer (EORTC) quality of life Web page. Available at: www.eortc.be/home/qol. Accessed April 4, 2003
  127. Kaasa T, Wessel J. The Edmonton Functional Assessment Tool (further development and validation for use in palliative care). J Palliat Care. 2001;17:5–11
  128. 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). J Clin Oncol. 2002;20:567–573
  129. Erkurt E, Erkisi M, Tunali C. Supportive treatment in weight-losing cancer patients due to the additive adverse effects of radiation treatment and/or chemotherapy. J Exp Clin Cancer Res. 2000;19:431–439
  130. Nelson KA, Walsh D, Hussein M. A phase II study of low-dose megestrol acetate using twice-daily dosing for anorexia in non-hormonally dependent cancer. Am J Hosp Palliat Care. 2002;19:206–210
  131. Nowicki M, Bryc W, Kokot F. Hormonal regulation of appetite and body mass in patients with advanced prostate cancer treated with combined androgen blockade. J Endocrinol Invest. 2001;24:31–36
  132. Weisberg J, Wanger J, Olson J, et al.  Megestrol acetate stimulates weight gain and ventilation in underweight COPD patients. Chest. 2002;121:1070–1078
  133. Yeh SS, Wu SY, Lee TP, et al.  Improvement in quality-of-life measures and stimulation of weight gain after treatment with megestrol acetate oral suspension in geriatric cachexia (results of a double-blind, placebo-controlled study). J Am Geriatr Soc. 2000;48:485–492
  134. Basson BR, Kinon BJ, Taylor CC, et al.  Factors influencing acute weight change in patients with schizophrenia treated with olanzapine, haloperidol, or risperidone. J Clin Psychiatry. 2001;62:231–238
  135. McIntyre RS, McCann SM, Kennedy SH. Weight change and atypical antipsychotic treatment in patients with schizophrenia. J Clin Psychiatry. 2001;62:41–44
  136. Jones B, Basson BR, Walker DJ, et al.  Weight change and atypical antipsychotic treatment in patients with schizophrenia. J Clin Psychiatry. 2001;62(Suppl 2):41–44
  137. Jatoi A, Daly BD, Hughes VA, et al.  Do patients with nonmetastatic non-small cell lung cancer demonstrate altered resting energy expenditure?. Ann Thorac Surg. 2001;72:348–351
  138. MacIntosh CG, Morley JE, Wishart J, et al.  Effect of exogenous cholecystokinin (CCK)-8 on food intake and plasma CCK, leptin, and insulin concentrations in older and young adults (evidence for increased CCK activity as a cause of the anorexia of aging). J Clin Endocrinol Metab. 2001;86:5830–5837
  139. MacIntosh CG, Horowitz M, Verhagen MA, et al.  Effect of small intestinal nutrient infusion on appetite, gastrointestinal hormone release, and gastric myoelectrical activity in young and older men. Am J Gastroenterol. 2001;96:997–1007
  140. van Bokhorst-De Van Der Schueren MA, Quak JJ, von Blomberg-van der Flier BM, et al.  Effect of perioperative nutrition, with and without arginine supplementation, on nutritional status, immune function, postoperative morbidity, and survival in severely malnourished head and neck cancer patients. Am J Clin Nutr. 2001;73:323–332
  141. Clark RH, Feleke G, Din M, et al.  Nutritional treatment for acquired immunodeficiency virus-associated wasting using beta-hydroxy beta-methylbutyrate, glutamine, and arginine (a randomized, double-blind, placebo-controlled study). JPEN J Parenter Enteral Nutr. 2000;24:133–139
  142. Hiroshige K, Sonta T, Suda T, et al.  Oral supplementation of branched-chain amino acid improves nutritional status in elderly patients on chronic haemodialysis. Nephrol Dial Transplant. 2001;16:1856–1862
  143. Tipton KD, Rasmussen BB, Miller SL, et al.  Timing of amino acid-carbohydrate ingestion alters anabolic response of muscle to resistance exercise. Am J Physiol Endocrinol Metab. 2001;281:E197–E206
  144. Carroll PV. Treatment with growth hormone and insulin-like growth factor-I in critical illness. Best Pract Res Clin Endocrinol Metab. 2001;15:435–451
  145. Crown AL, Cottle K, Lightman SL, et al.  What is the role of the insulin-like growth factor system in the pathophysiology of cancer cachexia, and how is it regulated?. Clin Endocrinol (Oxf). 2002;56:723–733
  146. Brink M, Anwar A, Delafontaine P. Neurohormonal factors in the development of catabolic/anabolic imbalance and cachexia. Int J Cardiol. 2002;85:111–121
  147. Esmarck B, Andersen JL, Olsen S, et al.  Timing of postexercise protein intake is important for muscle hypertrophy with resistance training in elderly humans. J Physiol. 2001;535:301–311
  148. Lang CH, Frost RA. Role of growth hormone, insulin-like growth factor-I, and insulin-like growth factor binding proteins in the catabolic response to injury and infection. Curr Opin Clin Nutr Metab Care. 2002;5:271–279
  149. Mauras N, George D, Evans J, et al.  Growth hormone has anabolic effects in glucocorticosteroid-dependent children with inflammatory bowel disease (a pilot study). Metabolism. 2002;51:127–135
  150. Schulze PC, Gielen S, Schuler G, Hambrecht R. Chronic heart failure and skeletal muscle catabolism (effects of exercise training). Int J Cardiol. 2002;85:141–149
  151. Barber MD, Fearon KC. Tolerance and incorporation of a high-dose eicosapentaenoic acid diester emulsion by patients with pancreatic cancer cachexia. Lipids. 2001;36:347–351
  152. Barber MD, Ross JA, Fearon KC. Disordered metabolic response with cancer and its management. World J Surg. 2000;24:681–689
  153. Sauer LA, Dauchy RT, Blask DE. Mechanism for the antitumor and anticachectic effects of n-3 fatty acids. Cancer Res. 2000;60:5289–5295
  154. Sharma R, Anker SD. Cytokines, apoptosis and cachexia (the potential for TNF antagonism). Int J Cardiol. 2002;85:161–171
  155. von Haehling S, Genth-Zotz S, Anker SD, Volk HD. Cachexia (a therapeutic approach beyond cytokine antagonism). Int J Cardiol. 2002;85:173–183
  156. Anker SD, Coats AJ. How to RECOVER from RENAISSANCE? The significance of the results of RECOVER, RENAISSANCE, RENEWAL and ATTACH. Int J Cardiol. 2002;86:123–130
  157. Mesa JL, Ruiz JR, Gonzalez-Gross MM, et al.  Oral creatine supplementation and skeletal muscle metabolism in physical exercise. Sports Med. 2002;32:903–944
  158. Lipshultz SE, Lipsitz SR, Sallan SE, et al.  Long-term enalapril therapy for left ventricular dysfunction in Doxorubicin-treated survivors of childhood cancer. J Clin Oncol. 2002;20:4517–4522
  159. Latini R, Masson S, Anand I, et al.  Effects of valsartan on circulating brain natriuretic peptide and norepinephrine in symptomatic chronic heart failure (the Valsartan Heart Failure Trial (Val-HeFT)). Circulation. 2002;106:2454–2458
  160. Palazzuoli A, Bruni F, Puccetti L, et al.  Effects of carvedilol on left ventricular remodeling and systolic function in elderly patients with heart failure. Eur J Heart Fail. 2002;4:765–770
  161. Gould PA, Kaye DM. Clinical treatment regimens for chronic heart failure (a review). Expert Opin Pharmacother. 2002;3:1569–1576
  162. Walsh TD, Rivera NI. Adenosine triphosphate for cancer cachexia. Curr Oncol Rep. 2002;4:231–232
  163. Agteresch HJ, Dagnelie PC, van der Gaast A, et al.  Randomized clinical trial of adenosine 5′-triphosphate in patients with advanced non-small-cell lung cancer. J Natl Cancer Inst. 2000;92:321–328
  164. Aghajanian C, Soignet S, Dizon DS, et al.  A phase I trial of the novel proteasome inhibitor PS341 in advanced solid tumor malignancies. Clin Cancer Res. 2002;8:2505–2511
  165. Hyltander A, Daneryd P, Sandstrom R, et al.  Beta-adrenoceptor activity and resting energy metabolism in weight losing cancer patients. Eur J Cancer. 2000;36:330–334
  166. Gambardella A, Tortoriello R, Pesce L, et al.  Intralipid infusion combined with propranolol administration has favorable metabolic effects in elderly malnourished cancer patients. Metabolism. 1999;48:291–297
  167. Louis A, Cleland JG, Crabbe S, et al.  Clinical trials update (CAPRICORN, COPERNICUS, MIRACLE, STAF, RITZ-2, RECOVER and RENAISSANCE and cachexia and cholesterol in heart failure. Highlights of the Scientific Sessions of the American College of Cardiology, 2001). Eur J Heart Fail. 2001;3:381–387
  168. Daneryd P. Epoetin alfa for protection of metabolic and exercise capacity in cancer patients. Semin Oncol. 2002;29(Suppl 8):69–74

PII: S1072-7515(03)00382-X

doi: 10.1016/S1072-7515(03)00382-X

Journal of the American College of Surgeons
Volume 197, Issue 1 , Pages 143-161 , July 2003