Pharmaco-Nutritional Supports for the Treatment of Cancer Cachexia

  • Max Dahele
  • Kenneth C. H. Fearon


Cancer cachexia is a major symptom burden for patients with cancer.Cachexia occurs in up to one half of all patients diagnosed with cancer [1] and is more frequent in patients with lung and upper-gastrointestinal cancer.Cancer cachexia results from the interaction of the host and the tumour. However, the nature of this interaction is incompletely understood [2] [5], including the dynamics of the host response (activation of the systemic inflammatory response, metabolic, immune and neuroendocrine changes) and those tumour characteristics or tumour-derived products that influence expression of the syndrome (e.g. proteolysis-inducing factor [PIF]). The relative importance of individual mediators and pathways in different patients or tumour types is unclear, as is the reason why individuals with apparently similar tumours should show considerable variation in their tendency to develop cachexia.As ability to discriminate the relative importance in vivo of different mediators improves, so too should the ability to develop appropriately targeted therapy.


Clin Oncol Darbepoetin Alfa Cancer Cachexia Creatine Supplementation North Central Cancer Treatment Group 
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.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Palesty JA, Dudrick SJ (2003) What we have learned about cachexia in gastrointestinal cancer. Dig Dis 21:198–213PubMedCrossRefGoogle Scholar
  2. 2.
    Inui A (2002) Cancer anorexia-cachexia syndrome: current issues in research and management. CA Cancer J Clin 52:72–91PubMedGoogle Scholar
  3. 3.
    Crown AL, Cottle K, Lightman SL et al (2002) 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) 56:723–733CrossRefGoogle Scholar
  4. 4.
    Brink M, Anwar A, Delafontaine P (2002) Neurohormonal factors in the development of catabolic/anabolic imbalance and cachexia. Int J Cardiol 85:111–121; discussion 121–124PubMedCrossRefGoogle Scholar
  5. 5.
    Heber D, Byerley LO, Tchekmedyian NS (1992) Hormonal and metabolic abnormalities in the malnourished cancer patient: effects on host-tumor interaction. JPEN J Parenter Enterai Nutr 16:60S–64SGoogle Scholar
  6. 6.
    Dewys WD, Begg C, Lavin PT et al (1980) Prognostic effect of weight loss prior to chemotherapy in cancer patients. Eastern Cooperative Oncology Group. Am JMed 69:491Google Scholar
  7. 7.
    Tohgo A, Kumazawa E, Akahane K et al (2002) Anticancer drugs that induce cancer-associated cachectic syndromes. Expert Rev Anticancer Ther 2:121–129PubMedCrossRefGoogle Scholar
  8. 8.
    Bauer J, Capra S (2003) Comparison of a malnutrition screening tool with subjective global assessment in hospitalised patients with cancer—sensitivity and specificity. Asia Pac J Clin Nutr 12:257–260PubMedGoogle Scholar
  9. 9.
    Ottery FD (1996) Definition of standardized nutritional assessment and interventional pathways in oncology. Nutrition 12:S15–S19PubMedGoogle Scholar
  10. 10.
    Davis CH (1994) The report to Congress on the appropriate federal role in assuring access by medical students, residents, and practicing physicians to adequate training in nutrition. Public Health Rep 109:824–826PubMedGoogle Scholar
  11. 11.
    Werneke U, Earl J, Seydel C et al (2004) Potential health risks of complementary alternative medicines in cancer patients. Br J Cancer 90:408–413PubMedCrossRefGoogle Scholar
  12. 12.
    Cassidy A (2003) Are herbal remedies and dietary supplements safe and effective for breast cancer 612 patients? Breast Cancer Res 5:300–302PubMedCrossRefGoogle Scholar
  13. 13.
    Jatoi A, Daly BD, Hughes VA et al (2001) Do patients with nonmetastatic non-small cell lung cancer demonstrate altered resting energy expenditure? Ann Thorac Surg 72:348–351PubMedCrossRefGoogle Scholar
  14. 14.
    Ardies CM (2002) Exercise, cachexia, and cancer therapy: a molecular rationale. Nutr Cancer 42:143–157PubMedCrossRefGoogle Scholar
  15. 15.
    Al-Majid S, McCarthy DO (2001) Cancer-induced fatigue and skeletal muscle wasting: the role of exercise. Biol Res Nurs 2:186–197PubMedCrossRefGoogle Scholar
  16. 16.
    Al-Majid S, McCarthy DO (2001) Resistance exercise training attenuates wasting of the extensor digitorum longus muscle in mice bearing the colon-26 adenocarcinoma. Biol Res Nurs 2:155–166PubMedCrossRefGoogle Scholar
  17. 17.
    Daneryd P (2002) Epoetin alfa for protection of metabolic and exercise capacity in cancer patients. Semin Oncol 29:69–74PubMedGoogle Scholar
  18. 18.
    Bosaeus I, Daneryd P, Svanberg E, Lundholm K (2001) Dietary intake and resting energy expenditure in relation to weight loss in unselected cancer patients. Int J Cancer 93:380–383PubMedCrossRefGoogle Scholar
  19. 19.
    Braunschweig C, Gomez S, Sheean PM (2000) Impact of declines in nutritional status on outcomes in adult patients hospitalized for more than 7 days. J Am Diet Assoc 100:1316–1322PubMedCrossRefGoogle Scholar
  20. 20.
    Ravera E, Bozzetti F, Ammatuna M, Radaelli G (1987) Impact of hospitalization on the nutritional status of cancer patients. Tumori 73:375–380PubMedGoogle Scholar
  21. 21.
    Laviano A, Meguid MM, Rossi-Fanelli F (2003) Cancer anorexia: clinical implications, pathogenesis, and therapeutic strategies. Lancet Oncol 4:686–694PubMedCrossRefGoogle Scholar
  22. 22.
    McNurlan MA, Heys SD, Park KG et al (1994) Tumour and host tissue responses to branchedchain amino acid supplementation of patients with cancer. Clin Sci (Lond) 86:339–345Google Scholar
  23. 23.
    Heys SD, Park KG, McNurlan MA et al (1991) Stimulation of protein synthesis in human tumours by parenteral nutrition: evidence for modulation of tumour growth. Br J Surg 78:483–487PubMedCrossRefGoogle Scholar
  24. 24.
    Park KG, Heys SD, Blessing K et al (1992) Stimulation of human breast cancers by dietary Larginine. Clin Sci (Lond) 82:413–417Google Scholar
  25. 25.
    Preston T, Slater C, McMillan DC et al (1998) Fibrinogen synthesis is elevated in fasting cancer patients with an acute phase response. J Nutr 128:1355–1360PubMedGoogle Scholar
  26. 26.
    Hochwald SN, Harrison LE, Port JL et al (1996) Depletion of high energy phosphate compounds in the tumor-bearing state and reversal after tumor resection. Surgery 120:534–541PubMedCrossRefGoogle Scholar
  27. 27.
    Donaldson SS, Lenon RA (1979) Alterations of nutritional status: impact of chemotherapy and radiation therapy. Cancer 43:2036–2052PubMedCrossRefGoogle Scholar
  28. 28.
    Samuels SE, Knowles AL, Tilignac T et al (2000) Protein metabolism in the small intestine during cancer cachexia and chemotherapy in mice. Cancer Res 60:4968–4974PubMedGoogle Scholar
  29. 29.
    Nelson K, Walsh D, Sheehan F (2002) Cancer and chemotherapy-related upper gastrointestinal symptoms: the role of abnormal gastric motor function and its evaluation in cancer patients. Support Care Cancer 10:455–461PubMedCrossRefGoogle Scholar
  30. 30.
    Lawson DH, Nixon DW, Kutner MH et al (1981) Enterai versus parenteral nutritional support in cancer patients. Cancer Treat Rep 65:101–106PubMedGoogle Scholar
  31. 31.
    Mercadante S (1998) Parenteral versus enterai nutrition in cancer patients: indications and practice. Support Care Cancer 6:85–93PubMedCrossRefGoogle Scholar
  32. 32.
    Torosian MH, Jalali S, Nguyen HQ (1990) Protein intake and 5-fluorouracil toxicity in tumor-bearing animals. J Surg Res 49:298–301PubMedCrossRefGoogle Scholar
  33. 33.
    Torosian MH, Mullen JL, Miller EE et al (1988) Reduction of methotrexate toxicity with improved nutritional status in tumor-bearing animals. Cancer 61:1731–1735PubMedCrossRefGoogle Scholar
  34. 34.
    De Cicco M, Panarello G, Fantin D et al (1993) Parenteral nutrition in cancer patients receiving chemotherapy: effects on toxicity and nutritional status. JPEN J Parenter Enterai Nutr 17:513–518Google Scholar
  35. 35.
    McGeer AJ, Detsky AS, O’Rourke K (1990) Parenteral nutrition in cancer patients undergoing chemotherapy: a meta-analysis. Nutrition 6:233–240PubMedGoogle Scholar
  36. 36.
    Chlebowski RT (1985) Critical evaluation of the role of nutritional support with chemotherapy. Cancer 55:268–272PubMedCrossRefGoogle Scholar
  37. 37.
    Evans WK, Nixon DW, Daly JM et al (1987) A randomized study of oral nutritional support versus ad lib nutritional intake during chemotherapy for advanced colorectal and non-small-cell lung cancer. J Clin Oncol 5:113–124PubMedGoogle Scholar
  38. 38.
    Ovesen L, Allingstrup L, Hannibal J et al (1993) Effect of dietary counseling on food intake, body weight, response rate, survival, and quality of life in cancer patients undergoing chemotherapy: a prospective, randomized study. J Clin Oncol 11:2043–2049PubMedGoogle Scholar
  39. 39.
    Fearon KC, Von Meyenfeldt MF, Moses AG 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 cancer cachexia: a randomised double blind trial. Gut 52:1479–1486PubMedCrossRefGoogle Scholar
  40. 40.
    Cohn SH, Gartenhaus W, Vartsky D et al (1981) Body composition and dietary intake in neoplastic disease. Am J Clin Nutr 34:1997–2004PubMedGoogle Scholar
  41. 41.
    Shaw JH (1988) Influence of stress, depletion, and/or malignant disease on the responsiveness of surgical patients to total parenteral nutrition. Am J Clin Nutr 48:144–147PubMedGoogle Scholar
  42. 42.
    Jeevanandam M, Legaspi A, Lowry SF et al (1988) Effect of total parenteral nutrition on whole body protein kinetics in cachectic patients with benign or malignant disease. JPEN J Parenter Enterai Nutr 12:229–236Google Scholar
  43. 43.
    Hyltander A, Warnold I, Eden E, Lundholm K (1991) Effect on whole-body protein synthesis after institution of intravenous nutrition in cancer and noncancer patients who lose weight. Eur J Cancer 27:16–21PubMedGoogle Scholar
  44. 44.
    Bennegard K, Eden E, Ekman L et al (1983) Metabolic response of whole body and peripheral tissues to enterai nutrition in weight-losing cancer and noncancer patients. Gastroenterology 85:92–99PubMedGoogle Scholar
  45. 45.
    Edstrom S, Bennegard K, Eden E, Lundholm K (1982) Energy and tissue metabolism in patients with cancer during nutritional support. Arch Otolaryngol 108:697–699PubMedGoogle Scholar
  46. 46.
    Nixon DW, Lawson DH, Kutner M et al (1981) Hyperalimentation of the cancer patient with protein-calorie undernutrition. Cancer Res 41:2038–2045PubMedGoogle Scholar
  47. 47.
    Barber MD, Preston T, McMillan DC et al (2004) Modulation of the liver export protein synthetic response to feeding by an n-3 fatty-acid-enriched nutritional supplement is associated with anabolism in cachectic cancer patients. Clin Sci (Lond) 106:359–364Google Scholar
  48. 48.
    Heys SD, Walker LG, Smith I, Eremin O (1999) Enterai nutritional supplementation with key nutrients in patients with critical illness and cancer: a meta-analysis of randomized controlled clinical trials. Ann Surg 229:467–477PubMedCrossRefGoogle Scholar
  49. 49.
    McCarthy DO (2003) Rethinking nutritional support for persons with cancer cachexia. Biol Res Nurs 5:3–17PubMedCrossRefGoogle Scholar
  50. 50.
    Tisdale MJ, Brennan RA (1988) A comparison of long-chain triglycerides and medium-chain triglycerides on weight loss and tumour size in a cachexia model. Br J Cancer 58:580–583PubMedGoogle Scholar
  51. 51.
    Smith HJ, Greenberg NA, Tisdale MJ (2004) Effect of eicosapentaenoic acid, protein and amino acids on protein synthesis and degradation in skeletal muscle of cachectic mice. Br J Cancer 91:408–412PubMedGoogle Scholar
  52. 52.
    Ross JA, Fearon KC (2002) Eicosanoid-dependent cancer cachexia and wasting. Curr Opin Clin Nutr Metab Care 5:241–248PubMedCrossRefGoogle Scholar
  53. 53.
    Calder PC (2002) Dietary modification of inflammation with lipids. Proc Nutr Soc 61:345–358PubMedCrossRefGoogle Scholar
  54. 54.
    Grimble RF, Howell WM, O’Reilly G et al (2002) The ability of fish oil to suppress tumor necrosis factor alpha production by peripheral blood mononuclear cells in healthy men is associated with polymorphisms in genes that influence tumor necrosis factor alpha production. Am J Clin Nutr 76:454–459PubMedGoogle Scholar
  55. 55.
    Wigmore SJ, Fearon KC, Maingay JP, Ross JA (1999) Down-regulation of the acute-phase response in patients with pancreatic cancer cachexia receiving oral eicosapentaenoic acid is mediated via suppression of interleukin-6. Clin Sci (Lond) 92:215–221Google Scholar
  56. 56.
    Tisdale MJ (2004) Cancer cachexia. Langenbecks Arch Surg 389:299–305PubMedCrossRefGoogle Scholar
  57. 57.
    Lazarus DD, Destree AT, Mazzola LM et al (1999) A new model of cancer cachexia: contribution of the ubiquitin-proteasome pathway. Am J Physiol 277:E332–E341PubMedGoogle Scholar
  58. 58.
    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 89:1116–1122PubMedCrossRefGoogle Scholar
  59. 59.
    Togni V, Ota CC, Folador A et al (2003) Cancer cachexia and tumor growth reduction in Walker 256 tumor-bearing rats supplemented with N-3 polyunsaturated fatty acids for one generation. Nutr Cancer 46:52–58PubMedCrossRefGoogle Scholar
  60. 60.
    Jho DH, Babcock TA, Tevar R et al (2002) Eicosapentaenoic acid supplementation reduces tumor volume and attenuates cachexia in a rat model of progressive non-metastasizing malignancy. JPEN J Parenter Enterai Nutr 26:291–297Google Scholar
  61. 61.
    Hardman WE, Moyer MP, Cameron IL (2002) Consumption of an omega-3 fatty acids product, INCELL AAFA, reduced side-effects of CPT-11 (irinotecan) in mice. Br J Cancer 86:983–988PubMedCrossRefGoogle Scholar
  62. 62.
    Hardman WE (2002) Omega-3 fatty acids to augment cancer therapy. J Nutr 132:3508S–3512SPubMedGoogle Scholar
  63. 63.
    Barber MD, Fearon KC (2001) Tolerance and incorporation of a high-dose eicosapentaenoic acid diester emulsion by patients with pancreatic cancer cachexia. Lipids 36:347–351PubMedCrossRefGoogle Scholar
  64. 64.
    Wigmore SJ, Barber MD, Ross JA et al (2000) Effect of oral eicosapentaenoic acid on weight loss in patients with pancreatic cancer. Nutr Cancer 36:177–184PubMedCrossRefGoogle Scholar
  65. 65.
    Moses AW, Slater C, Preston T et al (2004) 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. Br J Cancer 90:996–1002PubMedCrossRefGoogle Scholar
  66. 66.
    Ferrando AA, Stuart CA, Sheffield-Moore M, Wolfe RR (1999) Inactivity amplifies the catabolic response of skeletal muscle to cortisol. J Clin Endocrinol Metab 84:3515–3521PubMedCrossRefGoogle Scholar
  67. 67.
    Jatoi A, Rowland KM, Loprinzi CL et al (2003) An eicosapentaenoic acid (EPA)-enriched supplement versus megestrol acetate (MA) versus both for patients with cancer-associated wasting. A collaborative effort from the North Central Cancer Treatment Group (NCCTG) and the National Cancer Institute of Canada. Proc Am Soc Clin Oncol 22:743 (abs 2987)Google Scholar
  68. 68.
    Bruera E, Strasser F, Palmer JL et al (2003) 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 21:129–134PubMedCrossRefGoogle Scholar
  69. 69.
    Clark RH, Feleke G, Din M et al (2000) Nutritional treatment for acquired immunodeficiency virusassociated wasting using beta-hydroxy beta-methylbutyrate, glutamine, and arginine: a randomized, double-blind, placebo-controlled study. JPEN J Parenter Enterai Nutr 24:133–139Google Scholar
  70. 70.
    May PE, Barber A, D’Olimpio JT et al (2002) Reversal of cancer-related wasting using oral supplementation with a combination of beta-hydroxy-614 beta-methylbutyrate, arginine, and glutamine. Am J Surg 183:471–479PubMedCrossRefGoogle Scholar
  71. 71.
    Gomes-Marcondes MC, Ventrucci G, Toledo MT et al (2003) A leucine-supplemented diet improved protein content of skeletal muscle in young tumor-bearing rats. Braz J Med Biol Res 36:1589–1594PubMedCrossRefGoogle Scholar
  72. 72.
    Bartlett DL, Charland S, Torosian MH (1995) Effect of glutamine on tumor and host growth. Ann Surg Oncol 2:71–76PubMedCrossRefGoogle Scholar
  73. 73.
    Rathmacher JA, Nissen S, Panton L et al (2004) Supplementation with a combination of betahydroxy-beta-methylbutyrate (HMB), arginine, and glutamine is safe and could improve hematological parameters. JPEN J Parenter Enterai Nutr 28:65–75Google Scholar
  74. 74.
    Yoshida S, Kaibara A, Ishibashi N, Shirouzu K (2001) Glutamine supplementation in cancer patients. Nutrition 17:766–768PubMedCrossRefGoogle Scholar
  75. 75.
    Calder PC (2003) Immunonutrition. BMJ 327:117–118PubMedCrossRefGoogle Scholar
  76. 76.
    McCowen KC, Bistrian BR (2003) Immunonutrition: problematic or problem solving? Am J Clin Nutr 77:764–770PubMedGoogle Scholar
  77. 77.
    Argiles JM, Almendro V, Busquets S, Lopez-Soriano FJ (2004) The pharmacological treatment of cachexia. Curr Drug Targets 5:265–277PubMedCrossRefGoogle Scholar
  78. 78.
    MacDonald N, Easson AM, Mazurak VC et al (2003) Understanding and managing cancer cachexia. J Am Coll Surg 197:143–161PubMedCrossRefGoogle Scholar
  79. 79.
    Strasser F, Bruera ED (2002) Update on anorexia and cachexia. Hematol Oncol Clin North Am 16:589–617PubMedCrossRefGoogle Scholar
  80. 80.
    Pascual Lopez A, Roquei Figuls M, Urrutia Cuchi G et al (2004) Systematic review of megestrol acetate in the treatment of anorexia-cachexia syndrome. J Pain Symptom Manage 27:360–369PubMedCrossRefGoogle Scholar
  81. 81.
    Aisner J, Parnes H, Tait N et al (1990) Appetite stimulation and weight gain with megestrol acetate. Semin Oncol 17:2–7PubMedGoogle Scholar
  82. 82.
    De Conno F, Martini C, Zecca E et al (1998) Megestrol acetate for anorexia in patients with faradvanced cancer: a double-blind controlled clinical trial. Eur J Cancer 34:1705–1709PubMedCrossRefGoogle Scholar
  83. 83.
    Bruera E, Ernst S, Hagen N et al (1998) Effectiveness of megestrol acetate in patients with advanced cancer: a randomized, double-blind, crossover study. Cancer Prev Control 2:74–78PubMedGoogle Scholar
  84. 84.
    Lambert CP, Sullivan DH, Freeling SA et al (2002) 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 87:2100–2106PubMedCrossRefGoogle Scholar
  85. 85.
    Loprinzi CL, Schaid DJ, Dose AM et al (1993) Bodycomposition changes in patients who gain weight while receiving megestrol acetate. J Clin Oncol 11:152–154PubMedGoogle Scholar
  86. 86.
    Oster MH, Enders SR, Samuels SJ et al (1994) Megestrol acetate in patients with AIDS and cachexia. Ann Intern Med 121:400–408PubMedGoogle Scholar
  87. 87.
    Von Roenn JH, Knopf K (1996) Anorexia/cachexia in patients with HIV: lessons for the oncologist. Oncology (Huntingt) 10:1049–1056; discussion 1062–1064, 1067–1068Google Scholar
  88. 88.
    Engelson ES, Pi-Sunyer FX, Kotler DP (1995) Effects of megestrol acetate therapy on body composition and circulating testosterone concentrations in patients with AIDS. AIDS 9:1107–1108PubMedGoogle Scholar
  89. 89.
    Beller E, Tattersall M, Lumley T et al (1997) Improved quality of life with megestrol acetate in patients with endocrine-insensitive advanced cancer: a randomised placebo-controlled trial. Australasian Megestrol Acetate Cooperative Study Group. Ann Oncol 8:277–283Google Scholar
  90. 90.
    Tomiska M, Tomiskova M, Salajka F et al (2003) Palliative treatment of cancer anorexia with oral suspension of megestrol acetate. Neoplasma 50:227–233PubMedGoogle Scholar
  91. 91.
    Vadell C, Segui MA, Gimenez-Arnau JM et al (1998) Anticachectic efficacy of megestrol acetate at different doses and versus placebo in patients with neoplastic cachexia. Am J Clin Oncol 21:347–351PubMedCrossRefGoogle Scholar
  92. 92.
    Meacham LR, Mazewski C, Krawiecki N (2003) Mechanism of transient adrenal insufficiency with megestrol acetate treatment of cachexia in children with cancer. J Pediatr Hematol Oncol 25:414–417PubMedCrossRefGoogle Scholar
  93. 93.
    Orme LM, Bond JD, Humphrey MS et al (2003) Megestrol acetate in pediatric oncology patients may lead to severe, symptomatic adrenal suppression. Cancer 98:397–405PubMedCrossRefGoogle Scholar
  94. 94.
    Rowland KM Jr, Loprinzi CL, Shaw EG et al (1996) 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 14:135–141PubMedGoogle Scholar
  95. 95.
    Mantovani G, Macciò A, Lai P et al (1998) Cytokine involvement in cancer anorexia/cachexia: role of megestrol acetate and medroxyprogesterone acetate on cytokine downregulation and improvement of clinical symptoms. Crit Rev Oncog 9:99–106PubMedGoogle Scholar
  96. 96.
    Helle SI, Lundgren S, Geisler S et al (1999) Effects of treatment with megestrol acetate on the insulin-like growth factor system: time and dose dependency. Eur J Cancer 35:1070–1075PubMedCrossRefGoogle Scholar
  97. 97.
    McCarthy HD, Crowder RE, Dryden S, Williams G (1994) Megestrol acetate stimulates food and water intake in the rat: effects on regional hypothalamic neuropeptide Y concentrations. Eur J Pharmacol 265:99–102PubMedCrossRefGoogle Scholar
  98. 98.
    Tassinari D, Fochessati F, Panzini I et al (2003) Rapid progression of advanced ‘hormone-resistant’ prostate cancer during palliative treatment with progestins for cancer cachexia. J Pain Symptom Manage 25:481–484PubMedCrossRefGoogle Scholar
  99. 99.
    Maltoni M, Nanni O, Scarpi E et al (2001) High-dose progestins for the treatment of cancer anorexiacachexia syndrome: a systematic review of randomised clinical trials. Ann Oncol 12:289–300PubMedCrossRefGoogle Scholar
  100. 100.
    Willox JC, Corr J, Shaw J et al (1984) Prednisolone as an appetite stimulant in patients with cancer. Br Med J (Clin Res Ed) 288:27CrossRefGoogle Scholar
  101. 101.
    Delia Cuna GR, Pellegrini A, Piazzi M (1989) Effect of methylprednisolone sodium succinate on quality of life in preterminal cancer patients: a placebo-controlled, multicenter study. The Methylprednisolone Preterminal Cancer Study Group. Eur J Cancer Clin Oncol 25:1817–1821CrossRefGoogle Scholar
  102. 102.
    Moertel CG, Schutt AJ, Reitemeier RJ, Hahn RG (1974) Corticosteroid therapy of preterminal gastrointestinal cancer. Cancer 33:1607–1609PubMedCrossRefGoogle Scholar
  103. 103.
    Jatoi A, Windschitl HE, Loprinzi CL et al (2002) Dronabinol versus megestrol acetate versus combination therapy for cancer-associated anorexia: a North Central Cancer Treatment Group study. J Clin Oncol 20:567–573PubMedCrossRefGoogle Scholar
  104. 104.
    Walsh D, Nelson KA, Mahmoud FA (2003) Established and potential therapeutic applications of cannabinoids in oncology. Support Care Cancer 11:137–143PubMedCrossRefGoogle Scholar
  105. 105.
    Kardinal CG, Loprinzi CL, Schaid DJ et al (1990) A controlled trial of cyproheptadine in cancer patients with anorexia and/or cachexia. Cancer 65:2657–2662PubMedCrossRefGoogle Scholar
  106. 106.
    Desport JC, Gory-Delabaere G, Blanc-Vincent MP et al (2003) Standards, options and recommendations for the use of appetite stimulants in oncology (2000). Br J Cancer 89(Suppl 1):S98–S100PubMedCrossRefGoogle Scholar
  107. 107.
    Basaria S, Wahlstrom JT, Dobs AS (2001) Clinical review 138: anabolic-androgenic steroid therapy in the treatment of chronic diseases. J Clin Endocrinol Metab 86:5108–5117PubMedCrossRefGoogle Scholar
  108. 108.
    Langer CJ, Hoffman JP, Ottery FD (2001) Clinical significance of weight loss in cancer patients: rationale for the use of anabolic agents in the treatment of cancer-related cachexia. Nutrition 17:S1–S2OPubMedCrossRefGoogle Scholar
  109. 109.
    Mudali S, Dobs AS (2004) Effects of testosterone on body composition of the aging male. Mech Ageing Dev 125:297–304PubMedCrossRefGoogle Scholar
  110. 110.
    Franchimont P, Kicovic PM, Mattei A, Roulier R (1978) Effects of oral testosterone undecanoate in hypogonadal male patients. Clin Endocrinol (Oxf) 9:313–320Google Scholar
  111. 111.
    Simons JP, Schols AM, Buurman WA, Wouters EF (1999) 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) 97:215–223CrossRefGoogle Scholar
  112. 112.
    Tchekmedyian S, Fesen M, Price LM, Ottery FD (2003) Ongoing placebo-controlled study of oxandrolone in cancer-related weight loss. Int J Radiat Oncol Biol Phys 57:S283–S284Google Scholar
  113. 113.
    Muurahainen N, Mulligan K (1998) Clinical trials update in human immunodeficiency virus wasting. Semin Oncol 25:104–111PubMedGoogle Scholar
  114. 114.
    Loprinzi CL, Kugler JW, Sloan JA et al (1999) Randomized comparison of megestrol acetate versus dexamethasone versus fluoxymesterone for the treatment of cancer anorexia/cachexia. J Clin Oncol 17:3299–3306PubMedGoogle Scholar
  115. 115.
    Binnerts A, Uitterlinden P, Hofland LJ et al (1990) The in vitro and in vivo effects of human growth hormone administration on tumor growth of rats bearing a transplantable rat pituitary tumor (7315b). Eur J Cancer 26:269–276PubMedGoogle Scholar
  116. 116.
    Bartlett DL, Stein TP, Torosian MH (1995) Effect of growth hormone and protein intake on tumor growth and host cachexia. Surgery 117:260–267PubMedCrossRefGoogle Scholar
  117. 117.
    Fiebig HH, Dengler W, Hendriks HR (2000) No evidence of tumor growth stimulation in human tumors in vitro following treatment with recombinant human growth hormone. Anticancer Drugs 11:659–664PubMedCrossRefGoogle Scholar
  118. 118.
    Ng B, Wolf RF, Weksler B et al (1993) Growth hormone administration preserves lean body mass in sarcoma-bearing rats treated with doxorubicin. Cancer Res 53:5483–5486PubMedGoogle Scholar
  119. 119.
    Torosian MH (1993) Growth hormone and prostate cancer growth and metastasis in tumor-bearing animals. J Pediatr Endocrinol 6:93–97PubMedGoogle Scholar
  120. 120.
    Mulligan K, Tai VW, Schambelan M (1999) Use of growth hormone and other anabolic agents in AIDS wasting. JPEN J Parenter Enterai Nutr 23:S202–S209Google Scholar
  121. 121.
    Bartlett DL, Charland S, Torosian MH (1994) Growth hormone, insulin, and somatostatin therapy of cancer cachexia. Cancer 73:1499–1504PubMedCrossRefGoogle Scholar
  122. 122.
    Piffar PM, Fernandez R, Tchaikovski O et al (2003) Naproxen, clenbuterol and insulin administration ameliorates cancer cachexia and reduces tumor growth in Walker 256 tumor-bearing rats. Cancer Lett 201:139–148PubMedCrossRefGoogle Scholar
  123. 123.
    Moley JF, Morrison SD, Norton JA (1985) Insulin reversal of cancer cachexia in rats. Cancer Res 45:4925–4931PubMedGoogle Scholar
  124. 124.
    Carbo N, Lopez-Soriano J, Tarrago T et al (1997) Comparative effects of beta2-adrenergic agonists on muscle waste associated with tumour growth. Cancer Lett 115:113–118PubMedCrossRefGoogle Scholar
  125. 125.
    Hyltander A, Svaninger G, LundholmT K (1993) The effect of clenbuterol on body composition in spontaneously eating tumour-bearing mice. Biosci Rep 13:325–331PubMedCrossRefGoogle Scholar
  126. 126.
    Zimmers TA, Davies MV, Koniaris LG et al (2002) Induction of cachexia in mice by systemically administered myostatin. Science 296:1486–1488PubMedCrossRefGoogle Scholar
  127. 127.
    Goldberg RM, Loprinzi CL, Mailliard JA et al (1995) Pentoxifylline for treatment of cancer anorexia and cachexia? A randomized, double-blind, placebo-controlled trial. J Clin Oncol 13:2856–2859PubMedGoogle Scholar
  128. 128.
    Kosty MP, Fleishman SB, Herndon JE 2nd et al (1994) Cisplatin, vinblastine, and hydrazine sulfate in advanced, non-small-cell lung cancer: a randomized placebo-controlled, double-blind phase III study of the Cancer and Leukemia Group B. J Clin Oncol 12:1113–1120PubMedGoogle Scholar
  129. 129.
    Loprinzi CL, Kuross SA, O’Fallon JR et al (1994) Randomized placebo-controlled evaluation of hydrazine sulfate in patients with advanced colorectal cancer. J Clin Oncol 12:1121–1125PubMedGoogle Scholar
  130. 130.
    Loprinzi CL, Goldberg RM, Su JQ et al (1994) Placebo-controlled trial of hydrazine sulfate in patients with newly diagnosed non-small-cell lung cancer. J Clin Oncol 12:1126–1129PubMedGoogle Scholar
  131. 131.
    Khan ZH, Simpson EJ, Cole AT et al (2003) Oesophageal cancer and cachexia: the effect of short-term treatment with thalidomide on weight loss and lean body mass. Aliment Pharmacol Ther 17:677–682PubMedCrossRefGoogle Scholar
  132. 132.
    Zhou S, Kestell P, Tingle MD, Paxton JW (2002) Thalidomide in cancer treatment: a potential role in the elderly? Drugs Aging 19:85–100PubMedCrossRefGoogle Scholar
  133. 133.
    Fanelli M, Sarmiento R, Gattuso D et al (2003) Thalidomide: a new anticancer drug? Expert Opin Investig Drugs 12:1211–1225PubMedCrossRefGoogle Scholar
  134. 134.
    Lissoni P (2002) Is there a role for melatonin in supportive care? Support Care Cancer 10:110–116PubMedCrossRefGoogle Scholar
  135. 135.
    Lissoni P, Barni S, Mandala M et al (1999) Decreased toxicity and increased efficacy of cancer chemotherapy using the pineal hormone melatonin in metastatic solid tumour patients with poor clinical status. Eur J Cancer 35:1688–1692PubMedCrossRefGoogle Scholar
  136. 136.
    Siegel SA, Shealy DJ, Nakada MT et al (1995) The mouse/human chimeric monoclonal antibody cA2 neutralizes TNF in vitro and protects transgenic mice from cachexia and TNF lethality in vivo. Cytokine 7:15–25PubMedCrossRefGoogle Scholar
  137. 137.
    Anker SD, Coats AJ (2002) How to RECOVER from RENAISSANCE? The significance of the results of RECOVER, RENAISSANCE, RENEWAL and ATTACH. Int J Cardiol 86:123–130PubMedCrossRefGoogle Scholar
  138. 138.
    Mann DL, McMurray JJ, Packer M et al (2004) Targeted anticytokine therapy in patients with chronic heart failure: results of the Randomized Etanercept Worldwide Evaluation (RENEWAL). Circulation 109:1594–1602PubMedCrossRefGoogle Scholar
  139. 139.
    Jho DH, Cole SM, Lee EM, Espat NJ (2004) Role of omega-3 fatty acid supplementation in inflammation and malignancy. Integr Cancer Ther 3:98–111PubMedCrossRefGoogle Scholar
  140. 140.
    Preston T, Fearon KC, McMillan DC et al (1995) Effect of ibuprofen on the acute-phase response and protein metabolism in patients with cancer and weight loss. Br J Surg 82:229–234PubMedCrossRefGoogle Scholar
  141. 141.
    Eli Y, Przedecki F, Levin G et al (2001) Comparative effects of indomethacin on cell proliferation and cell cycle progression in tumor cells grown in vitro and in vivo. Biochem Pharmacol 61:565–571PubMedCrossRefGoogle Scholar
  142. 142.
    Lundholm K, Daneryd P, Korner U et al (2004) Evidence that long-term COX-treatment improves energy homeostasis and body composition in cancer patients with progressive cachexia. Int J Oncol 24:505–512PubMedGoogle Scholar
  143. 143.
    Lundholm K, Gelin J, Hyltander A et al (1994) Antiinflammatory treatment may prolong survival in undernourished patients with metastatic solid tumors. Cancer Res 54:5602–5606PubMedGoogle Scholar
  144. 144.
    McMillan DC, Wigmore SJ, Fearon KC et al (1999) A prospective randomized study of megestrol acetate and ibuprofen in gastrointestinal cancer patients with weight loss. Br J Cancer 79:495–500PubMedCrossRefGoogle Scholar
  145. 145.
    Davis TW, Zweifel BS, O’Neal JM et al (2004) Inhibition of cyclooxygenase-2 by celecoxib reverses tumor-induced wasting. J Pharmacol Exp Ther 308:929–934PubMedCrossRefGoogle Scholar
  146. 146.
    Hussey HJ, Tisdale MJ (2000) Effect of the specific cyclooxygenase-2 inhibitor meloxicam on tumour growth and cachexia in a murine model. Int J Cancer 87:95–100PubMedCrossRefGoogle Scholar
  147. 147.
    Lundholm K, Daneryd P, Bosaeus I et al (2004) Palliative nutritional intervention in addition to cyclooxygenase and erythropoietin treatment for patients with malignant disease: effects on survival, metabolism, and function. Cancer 100:1967–1977PubMedCrossRefGoogle Scholar
  148. 148.
    McCarthy DO, Whitney P, Hitt A, Al-Majid S (2004) Indomethacin and ibuprofen preserve gastrocnemius muscle mass in mice bearing the colon-26 adenocarcinoma. Res Nurs Health 27:174–184PubMedCrossRefGoogle Scholar
  149. 149.
    Prisk V, Huard J (2003) Muscle injuries and repair: the role of prostaglandins and inflammation. Histol Histopathol 18:1243–1256PubMedGoogle Scholar
  150. 150.
    Bondesen BA, Mills ST, Kegley KM, Pavlath GK (2004) The COX-2 pathway is essential during early stages of skeletal muscle regeneration. Am J Physiol Cell Physiol 287:C475–C483PubMedCrossRefGoogle Scholar
  151. 151.
    Hamada K, Mikasa K, Yunou Y et al (2000) Adjuvant effect of clarithromycin on chemotherapy for murine lung cancer. Chemotherapy 46:49–61PubMedCrossRefGoogle Scholar
  152. 152.
    Ianaro A, Ialenti A, Maffia P et al (2000) Anti-inflammatory activity of macrolide antibiotics. J Pharmacol Exp Ther 292:156–163PubMedGoogle Scholar
  153. 153.
    Suzaki H, Asano K, Ohki S et al (1999) Suppressive activity of a macrolide antibiotic, roxithromycin, on pro-inflammatory cytokine production in vitro and in vivo. Mediators Inflamm 8:199–204PubMedCrossRefGoogle Scholar
  154. 154.
    Boffa DJ, Luan F, Thomas D et al (2004) Rapamycin inhibits the growth and metastatic progression of non-small cell lung cancer. Clin Cancer Res 10:293–300PubMedCrossRefGoogle Scholar
  155. 155.
    Sakamoto M, Mikasa K, Majima T et al (2001) Anticachectic effect of clarithromycin for patients with unresectable non-small cell lung cancer. Chemotherapy 47:444–451PubMedCrossRefGoogle Scholar
  156. 156.
    Mikasa K, Sawaki M, Kita E et al (1997) Significant survival benefit to patients with advanced nonsmall-cell lung cancer from treatment with clarithromycin. Chemotherapy 43:288–296PubMedCrossRefGoogle Scholar
  157. 157.
    Muscaritoli M, Costelli P, Bossola M et al (2003) Effects of simvastatin administration in an experimental model of cancer cachexia. Nutrition 19:936–939PubMedCrossRefGoogle Scholar
  158. 158.
    Onder G, Penninx BW, Balkrishnan R et al (2002) Relation between use of angiotensin-converting enzyme inhibitors and muscle strength and physical function in older women: an observational study. Lancet 359:926–930PubMedCrossRefGoogle Scholar
  159. 159.
    Yoshiji H, Kuriyama S, Fukui H (2002) Perindopril: possible use in cancer therapy. Anticancer Drugs 13:221–228PubMedCrossRefGoogle Scholar
  160. 160.
    Agteresch HJ, Burgers SA, van der Gaast A et al (2003) Randomized clinical trial of adenosine 5’-triphosphate on tumor growth and survival in advanced lung cancer patients. Anticancer Drugs 14:639–644PubMedCrossRefGoogle Scholar
  161. 161.
    Walsh TD, Rivera NI (2002) Adenosine triphosphate for cancer cachexia. Curr Oncol Rep 4:231–232PubMedCrossRefGoogle Scholar
  162. 162.
    Izquierdo M, Ibanez J, Gonzalez-Badillo JJ, Gorostiaga EM (2002) Effects of creatine supplementation on muscle power, endurance, and sprint performance. Med Sci Sports Exerc 34:332–343PubMedCrossRefGoogle Scholar
  163. 163.
    Lemon PW (2002) Dietary creatine supplementation and exercise performance: why inconsistent results? Can J Appl Physiol 27:663–681PubMedGoogle Scholar
  164. 164.
    Gotshalk LA, Volek JS, Staron RS et al (2002) Creatine supplementation improves muscular performance in older men. Med Sci Sports Exerc 34:537–543PubMedCrossRefGoogle Scholar
  165. 165.
    Terjung RL, Clarkson P, Eichner ER et al (2000) American College of Sports Medicine roundtable. The physiological and health effects of oral creatine supplementation. Med Sci Sports Exerc 32:706–717PubMedCrossRefGoogle Scholar
  166. 166.
    Evans WJ (2002) Physical function in men and women with cancer. Effects of anemia and conditioning. Oncology (Huntingt) 16:109–115Google Scholar
  167. 167.
    Kotasek D, Steger G, Faught W et al (2003) Aranesp 980291 Study Group. Darbepoetin alfa administered every 3 weeks alleviates anaemia in patients with solid tumours receiving chemotherapy; results of a double-blind, placebo-controlled, randomised study. Eur J Cancer 39:2026–2034PubMedCrossRefGoogle Scholar
  168. 168.
    Daneryd P, Svanberg E, Korner U et al (1998) Protection of metabolic and exercise capacity in unselected weight-losing cancer patients following treatment with recombinant erythropoietin: a randomized prospective study. Cancer Res Dec 58:5374–5379Google Scholar
  169. 169.
    Yasuda Y, Fujita Y, Matsuo T et al (2003) Erythropoietin regulates tumour growth of human malignancies. Carcinogenesis 24:1021–1029. Erratum in: Carcinogenesis 24:1567PubMedCrossRefGoogle Scholar
  170. 170.
    Brower V (2003) Erythropoietin may impair, not improve, cancer survival. Nat Med 9:1439PubMedCrossRefGoogle Scholar
  171. 171.
    Cahlin C, Gelin J, Delbro D et al (2000) 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 60:1742–1749PubMedGoogle Scholar
  172. 172.
    Terao H, Asano K, Kanai K et al (2003) Suppressive activity of macrolide antibiotics on nitric oxide production by lipopolysaccharide stimulation in mice. Mediators Inflamm 12:195–202PubMedCrossRefGoogle Scholar
  173. 173.
    Gambardella A, Tortoriello R, Pesce L et al (1999) Intralipid infusion combined with propranolol administration has favorable metabolic effects in elderly malnourished cancer patients. Metabolism 48:291–297PubMedCrossRefGoogle Scholar
  174. 174.
    Brooks SL, Neville AM, Rothwell NJ et al (1981) Sympathetic activation of brown-adipose-tissue thermogenesis in cachexia. Biosci Rep 1:509–517PubMedCrossRefGoogle Scholar
  175. 175.
    Hyltander A, Korner U, Lundholm KG (1993) Evaluation of mechanisms behind elevated energy expenditure in cancer patients with solid tumours. Eur J Clin Invest 23:46–52PubMedCrossRefGoogle Scholar
  176. 176.
    Hyltander A, Daneryd P, Sandstrom R et al (2000) Beta-adrenoceptor activity and resting energy metabolism in weight losing cancer patients. Eur J Cancer 36:330–334PubMedCrossRefGoogle Scholar
  177. 177.
    Pinto JA Jr, Folador A, Bonato SJ et al (2004) Fish oil supplementation in Fl generation associated with naproxen, clenbuterol, and insulin administration reduce tumor growth and cachexia in Walker 256 tumor-bearing rats. J Nutr Biochem 15:358–365PubMedCrossRefGoogle Scholar
  178. 178.
    Cerchietti LC, Navigante AH, Peluffo GD et al (2004) Effects of celecoxib, medroxyprogesterone, and dietary intervention on systemic syndromes in patients with advanced lung adenocarcinoma: a pilot study. J Pain Symptom Manage 27:85–95PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Italia 2006

Authors and Affiliations

  • Max Dahele
    • 1
  • Kenneth C. H. Fearon
    • 1
  1. 1.Department of Clinical and Surgical Sciences (Surgery)The University of EdinburghRoyal InfirmaryUK

Personalised recommendations