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Pharmacologic management of cancer anorexia/cachexia

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


The cancer-related anorexia/cachexia syndrome (CACS) is a hypercatabolic state characterized by anorexia and loss of body weight associated with reduced muscle mass and adipose tissue. In addition to a variable contribution from decreased energy intake, resting energy expenditure can be elevated in CACS in association with increases in both muscle protein breakdown and lipolysis, changes that appear to be due in part to an inflammatory response with the elaboration of cytokines, including tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and IL-1 beta. Tumor-elaborated factors, such as proteolysis-inducing factor and lipid-mobilizing factor, also may play an important role. Unlike starvation, weight loss in cancer arises both from loss of muscle and fat. (See "Pathogenesis, clinical features, and assessment of cancer cachexia".)

This topic review will cover pharmacologic treatment for patients with CACS. The clinical features and pathogenesis of CACS, nutritional support for patients with cancer, and a general discussion of assessment and management of anorexia/cachexia in palliative care patients with advanced life-threatening illness are provided elsewhere. (See "Pathogenesis, clinical features, and assessment of cancer cachexia" and "The role of parenteral and enteral/oral nutritional support in patients with cancer" and "Palliative care: Assessment and management of anorexia and cachexia".)


The cancer-related anorexia/cachexia syndrome (CACS) is frequently seen in patients with advanced cancer. One study evaluated 644 consecutive, mostly ambulatory cancer patients: decreased appetite, decreased food intake, and weight loss in excess of 5 percent of premorbid weight were present in more than one-half [1]. Furthermore, 54 percent were underweight when compared with the calculated ideal body weight.

Weight loss in CACS is a marker for both progression of the syndrome and for prognosis [2]. In a multi-institutional, retrospective review of 3047 clinical protocol cancer patients from the Eastern Cooperative Oncology Group, weight loss of more than 5 percent of premorbid weight prior to the initiation of chemotherapy was predictive of early mortality. Weight loss was independent of disease stage, tumor histology, and patient performance status in its predictive value [2]. There was also a trend towards lower response rates with the use of chemotherapy among weight-losing patients. This trend reached statistical significance only among patients with breast cancer.


All cancer patients should be assessed for nutritional status and weight loss. The clinical assessment for patients with anorexia or cachexia includes a careful history that is focused on nutritional issues including risk factors that compromise the ability to obtain or take in nutrition, and a physical examination focusing on loss of subcutaneous fat, muscle wasting (temporal region, deltoids, and quadriceps with loss of bulk and tone by palpation), edema (sacral or ankle), or ascites. The most commonly used objective measures of nutritional status are serial measurement of body weight and assessment of dietary intake, while subjective information on nutritional status can be provided by malnutritional assessment tools. Laboratory measures of nutritional status (eg, albumin, transferrin) are rarely needed for assessment of nutritional status, although some screening tools (eg, the Nutrition Risk Index) do include a measurement of serum albumin. These issues are all addressed in more detail elsewhere. (See "Palliative care: Assessment and management of anorexia and cachexia", section on 'Assessment'.)

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Literature review current through: Oct 2017. | This topic last updated: Jun 29, 2017.
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  1. Hashida H, Takabayashi A, Tokuhara T, et al. Integrin alpha3 expression as a prognostic factor in colon cancer: association with MRP-1/CD9 and KAI1/CD82. Int J Cancer 2002; 97:518.
  2. Dewys WD, Begg C, Lavin PT, et al. Prognostic effect of weight loss prior to chemotherapy in cancer patients. Eastern Cooperative Oncology Group. Am J Med 1980; 69:491.
  3. Ovesen L, Allingstrup L, Hannibal J, et al. 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 1993; 11:2043.
  4. Barber MD, Fearon KC, Delmore G, Loprinzi CL. Should cancer patients with incurable disease receive parenteral or enteral nutritional support? Eur J Cancer 1998; 34:279.
  5. Ruiz Garcia V, López-Briz E, Carbonell Sanchis R, et al. Megestrol acetate for treatment of anorexia-cachexia syndrome. Cochrane Database Syst Rev 2013; :CD004310.
  6. Moertel CG, Schutt AJ, Reitemeier RJ, Hahn RG. Corticosteroid therapy of preterminal gastrointestinal cancer. Cancer 1974; 33:1607.
  7. Bruera E, Roca E, Cedaro L, et al. Action of oral methylprednisolone in terminal cancer patients: a prospective randomized double-blind study. Cancer Treat Rep 1985; 69:751.
  8. Popiela T, Lucchi R, Giongo F. Methylprednisolone as palliative therapy for female terminal cancer patients. The Methylprednisolone Female Preterminal Cancer Study Group. Eur J Cancer Clin Oncol 1989; 25:1823.
  9. Loprinzi CL, Ellison NM, Schaid DJ, et al. Controlled trial of megestrol acetate for the treatment of cancer anorexia and cachexia. J Natl Cancer Inst 1990; 82:1127.
  10. 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.
  11. Yavuzsen T, Davis MP, Walsh D, et al. Systematic review of the treatment of cancer-associated anorexia and weight loss. J Clin Oncol 2005; 23:8500.
  12. Loprinzi CL, Michalak JC, Schaid DJ, et al. Phase III evaluation of four doses of megestrol acetate as therapy for patients with cancer anorexia and/or cachexia. J Clin Oncol 1993; 11:762.
  13. Vadell C, Seguí MA, Giménez-Arnau JM, et al. Anticachectic efficacy of megestrol acetate at different doses and versus placebo in patients with neoplastic cachexia. Am J Clin Oncol 1998; 21:347.
  14. Bruera E, Ernst S, Hagen N, et al. Effectiveness of megestrol acetate in patients with advanced cancer: a randomized, double-blind, crossover study. Cancer Prev Control 1998; 2:74.
  15. Pardo J, Mena AM, Motnsech L, et al. Megestrol acetate for anorexia in lung cancer patients undergoing radiation therapy. A randomized trial comparing the efficacy of two different doses in 130 patients (abstract). Proc Am Soc Clin Oncol 2003; 22:765a.
  16. Rowland KM Jr, 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.
  17. Leinung MC, Liporace R, Miller CH. Induction of adrenal suppression by megestrol acetate in patients with AIDS. Ann Intern Med 1995; 122:843.
  18. Mann M, Koller E, Murgo A, et al. Glucocorticoidlike activity of megestrol. A summary of Food and Drug Administration experience and a review of the literature. Arch Intern Med 1997; 157:1651.
  19. Dev R, Del Fabbro E, Bruera E. Association between megestrol acetate treatment and symptomatic adrenal insufficiency with hypogonadism in male patients with cancer. Cancer 2007; 110:1173.
  20. Simons JP, Aaronson NK, Vansteenkiste JF, et al. Effects of medroxyprogesterone acetate on appetite, weight, and quality of life in advanced-stage non-hormone-sensitive cancer: a placebo-controlled multicenter study. J Clin Oncol 1996; 14:1077.
  21. Abel EL. Effects of marihuana on the solution of anagrams, memory and appetite. Nature 1971; 231:260.
  22. 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.
  23. Cannabis-In-Cachexia-Study-Group, Strasser F, Luftner D, 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. J Clin Oncol 2006; 24:3394.
  24. Kardinal CG, Loprinzi CL, Schaid DJ, et al. A controlled trial of cyproheptadine in cancer patients with anorexia and/or cachexia. Cancer 1990; 65:2657.
  25. Moertel CG, Kvols LK, Rubin J. A study of cyproheptadine in the treatment of metastatic carcinoid tumor and the malignant carcinoid syndrome. Cancer 1991; 67:33.
  26. Lesser GJ, Case D, Ottery F, et al. A phase III randomized study comparing the effects of oxandrolone (Ox) and megestrol acetate (Meg) on lean body mass (LBM), weight (wt) and quality of life (QOL) in patients with solid tumors and weight loss receiving chemotherapy (abstract). J Clin Oncol 2008; 505:s.
  27. Dobs AS, Boccia RV, Croot CC, et al. Effects of enobosarm on muscle wasting and physical function in patients with cancer: a double-blind, randomised controlled phase 2 trial. Lancet Oncol 2013; 14:335.
  28. Crawford JC, Johnston MA, Hancock ML, et al. Enobosarm, a selective androgen receptor modulator (SARM) increases lean body mass in advanced NSCLC patients; updated results of two pivotal, international phase 3 trials (abstract). Data presented at the 2014 MASCC/ISOO International Symposium on Supportive Care in Cancer, Miami FL, 08 June, 2014. Abstract available online at http://mascc14.kenes.com/mascc14/CM.NET.WebUI/CM.NET.WEBUI.scpr/SCPRfunctiondetail.aspx?confID=05000000-0000-0000-0000-000000000080&sesID=05000000-0000-0000-0000-000000012890&absID=07000000-0000-0000-0000-000000055517 (Accessed on August 07, 2014).
  29. Bartlett DL, Stein TP, Torosian MH. Effect of growth hormone and protein intake on tumor growth and host cachexia. Surgery 1995; 117:260.
  30. Takala J, Ruokonen E, Webster NR, et al. Increased mortality associated with growth hormone treatment in critically ill adults. N Engl J Med 1999; 341:785.
  31. Kotler DP. Cachexia. Ann Intern Med 2000; 133:622.
  32. Strasser F, Lutz TA, Maeder MT, et al. Safety, tolerability and pharmacokinetics of intravenous ghrelin for cancer-related anorexia/cachexia: a randomised, placebo-controlled, double-blind, double-crossover study. Br J Cancer 2008; 98:300.
  33. Lundholm K, Gunnebo L, Körner U, et al. Effects by daily long term provision of ghrelin to unselected weight-losing cancer patients: a randomized double-blind study. Cancer 2010; 116:2044.
  34. Garcia JM, Friend J, Allen S. Therapeutic potential of anamorelin, a novel, oral ghrelin mimetic, in patients with cancer-related cachexia: a multicenter, randomized, double-blind, crossover, pilot study. Support Care Cancer 2013; 21:129.
  35. Garcia JM, Boccia RV, Graham CD, et al. Anamorelin for patients with cancer cachexia: an integrated analysis of two phase 2, randomised, placebo-controlled, double-blind trials. Lancet Oncol 2015; 16:108.
  36. Temel JS, Abernethy AP, Currow DC, et al. Anamorelin in patients with non-small-cell lung cancer and cachexia (ROMANA 1 and ROMANA 2): results from two randomised, double-blind, phase 3 trials. Lancet Oncol 2016; 17:519.
  37. Takayama K, Katakami N, Yokoyama T, et al. Anamorelin (ONO-7643) in Japanese patients with non-small cell lung cancer and cachexia: results of a randomized phase 2 trial. Support Care Cancer 2016; 24:3495.
  38. Currow D, Temel JS, Abernethy A, et al. ROMANA 3: a phase 3 safety extension study of anamorelin in advanced non-small-cell lung cancer (NSCLC) patients with cachexia. Ann Oncol 2017; 28:1949.
  39. Price SA, Tisdale MJ. Mechanism of inhibition of a tumor lipid-mobilizing factor by eicosapentaenoic acid. Cancer Res 1998; 58:4827.
  40. Wigmore SJ, Fearon KC, Maingay JP, Ross JA. 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) 1997; 92:215.
  41. Fearon KC, Von Meyenfeldt MF, Moses AG, 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; 52:1479.
  42. 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.
  43. 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. J Clin Oncol 2004; 22:2469.
  44. Fearon KC, Barber MD, Moses AG, et al. Double-blind, placebo-controlled, randomized study of eicosapentaenoic acid diester in patients with cancer cachexia. J Clin Oncol 2006; 24:3401.
  45. Murphy RA, Mourtzakis M, Chu QS, et al. Nutritional intervention with fish oil provides a benefit over standard of care for weight and skeletal muscle mass in patients with nonsmall cell lung cancer receiving chemotherapy. Cancer 2011; 117:1775.
  46. Ryan AM, Reynolds JV, Healy L, et al. Enteral nutrition enriched with eicosapentaenoic acid (EPA) preserves lean body mass following esophageal cancer surgery: results of a double-blinded randomized controlled trial. Ann Surg 2009; 249:355.
  47. van der Meij BS, Langius JA, Smit EF, et al. Oral nutritional supplements containing (n-3) polyunsaturated fatty acids affect the nutritional status of patients with stage III non-small cell lung cancer during multimodality treatment. J Nutr 2010; 140:1774.
  48. Weed HG, Ferguson ML, Gaff RL, et al. Lean body mass gain in patients with head and neck squamous cell cancer treated perioperatively with a protein- and energy-dense nutritional supplement containing eicosapentaenoic acid. Head Neck 2011; 33:1027.
  49. Murphy RA, Yeung E, Mazurak VC, Mourtzakis M. Influence of eicosapentaenoic acid supplementation on lean body mass in cancer cachexia. Br J Cancer 2011; 105:1469.
  50. Dewey A, Baughan C, Dean T, et al. Eicosapentaenoic acid (EPA, an omega-3 fatty acid from fish oils) for the treatment of cancer cachexia. Cochrane Database Syst Rev 2007; :CD004597.
  51. Lissoni P, Ardizzoia A, Perego MS, et al. Inhibition of tumor necrosis factor-alpha secretion by pentoxifylline in advanced cancer patients with abnormally high blood levels of tumor necrosis factor-alpha. J Biol Regul Homeost Agents 1993; 7:73.
  52. Dezube BJ, Sherman ML, Fridovich-Keil JL, et al. Down-regulation of tumor necrosis factor expression by pentoxifylline in cancer patients: a pilot study. Cancer Immunol Immunother 1993; 36:57.
  53. Goldberg RM, Loprinzi CL, Mailliard JA, et al. Pentoxifylline for treatment of cancer anorexia and cachexia? A randomized, double-blind, placebo-controlled trial. J Clin Oncol 1995; 13:2856.
  54. 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 N00C1 from the North Central Cancer Treatment Group. Cancer 2007; 110:1396.
  55. 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; 68:234.
  56. Gordon JN, Trebble TM, Ellis RD, et al. Thalidomide in the treatment of cancer cachexia: a randomised placebo controlled trial. Gut 2005; 54:540.
  57. Reid J, Mills M, Cantwell M, et al. Thalidomide for managing cancer cachexia. Cochrane Database Syst Rev 2012; :CD008664.
  58. Loprinzi CL, Goldberg RM, Su JQ, et al. Placebo-controlled trial of hydrazine sulfate in patients with newly diagnosed non-small-cell lung cancer. J Clin Oncol 1994; 12:1126.
  59. Loprinzi CL, Kuross SA, O'Fallon JR, et al. Randomized placebo-controlled evaluation of hydrazine sulfate in patients with advanced colorectal cancer. J Clin Oncol 1994; 12:1121.
  60. Kosty MP, Fleishman SB, Herndon JE 2nd, et al. 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 1994; 12:1113.
  61. Hainer MI, Tsai N, Komura ST, Chiu CL. Fatal hepatorenal failure associated with hydrazine sulfate. Ann Intern Med 2000; 133:877.
  62. Lundholm K, Körner U, Gunnebo L, et al. Insulin treatment in cancer cachexia: effects on survival, metabolism, and physical functioning. Clin Cancer Res 2007; 13:2699.
  63. 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.
  64. 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.
  65. Lissoni P, Paolorossi F, Tancini G, et al. Is there a role for melatonin in the treatment of neoplastic cachexia? Eur J Cancer 1996; 32A:1340.
  66. 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. J Pineal Res 1997; 23:15.
  67. Del Fabbro E, Dev R, Hui D, et al. Effects of melatonin on appetite and other symptoms in patients with advanced cancer and cachexia: a double-blind placebo-controlled trial. J Clin Oncol 2013; 31:1271.
  68. Riechelmann RP, Burman D, Tannock IF, et al. Phase II trial of mirtazapine for cancer-related cachexia and anorexia. Am J Hosp Palliat Care 2010; 27:106.
  69. Edelman MJ, Gandara DR, Meyers FJ, et al. Serotonergic blockade in the treatment of the cancer anorexia-cachexia syndrome. Cancer 1999; 86:684.
  70. Bruera E, Belzile M, Neumann C, et al. A double-blind, crossover study of controlled-release metoclopramide and placebo for the chronic nausea and dyspepsia of advanced cancer. J Pain Symptom Manage 2000; 19:427.
  71. Pisters PW, Pearlstone DB. Protein and amino acid metabolism in cancer cachexia: investigative techniques and therapeutic interventions. Crit Rev Clin Lab Sci 1993; 30:223.
  72. Kraft M, Kraft K, Gärtner S, et al. L-Carnitine-supplementation in advanced pancreatic cancer (CARPAN)--a randomized multicentre trial. Nutr J 2012; 11:52.
  73. Navari RM, Brenner MC. Treatment of cancer-related anorexia with olanzapine and megestrol acetate: a randomized trial. Support Care Cancer 2010; 18:951.
  74. McMillan DC, Wigmore SJ, Fearon KC, et al. A prospective randomized study of megestrol acetate and ibuprofen in gastrointestinal cancer patients with weight loss. Br J Cancer 1999; 79:495.
  75. Madeddu C, Dessì M, Panzone F, et al. Randomized phase III clinical trial of a combined treatment with carnitine + celecoxib ± megestrol acetate for patients with cancer-related anorexia/cachexia syndrome. Clin Nutr 2012; 31:176.
  76. Macciò A, Madeddu C, Gramignano G, et al. A randomized phase III clinical trial of a combined treatment for cachexia in patients with gynecological cancers: evaluating the impact on metabolic and inflammatory profiles and quality of life. Gynecol Oncol 2012; 124:417.
  77. Mantovani G, Macciò A, Madeddu C, et al. Randomized phase III clinical trial of five different arms of treatment in 332 patients with cancer cachexia. Oncologist 2010; 15:200.