Treatment of Cachexia: An Overview of Recent Developments

Journal of the American Medical Directors Association

Volumn 15, Issue 12, 2014, Pages 866-872

  von Haehling, Stephan ^a,b   Anker, Stefan D ^a  

^a UNIVERSITY MEDICAL CENTER GÖTTINGEN   (Germany)

^b CHARITÉ UNIVERSITÄTSMEDIZIN BERLIN   (Germany)

Author keywords

Cachexia; Cancer; Therapy; Wasting

Indexed keywords

ANABOLIC AGENT; ANAMORELIN; APPETITE STIMULANT; CARNITINE; ENOBOSARM; ESPINDOLOL; FORMOTEROL; GHRELIN; INTERLEUKIN 1ALPHA MONOCLONAL ANTIBODY; MEGESTROL ACETATE; MELATONIN; MONOCLONAL ANTIBODY; PENTOXIFYLLINE; TESTOSTERONE; THALIDOMIDE; UNCLASSIFIED DRUG; ANTIINFLAMMATORY AGENT;

ANDROGEN THERAPY; CACHEXIA; EXERCISE; GRIP STRENGTH; HAND GRIP; HOSPITAL PATIENT; HUMAN; MUSCLE MASS; MUSCLE STRENGTH; NONHUMAN; NUTRITIONAL SUPPORT; REVIEW; SURVIVAL; AGONISTS; COMPLICATION; NEOPLASM; PATHOPHYSIOLOGY; PHYSIOLOGY; QUALITY OF LIFE; SKELETAL MUSCLE;

ANABOLIC AGENTS; ANTI-INFLAMMATORY AGENTS; ANTIBODIES, MONOCLONAL; APPETITE STIMULANTS; CACHEXIA; GHRELIN; HUMANS; MUSCLE STRENGTH; MUSCLE, SKELETAL; NEOPLASMS; NUTRITIONAL SUPPORT; QUALITY OF LIFE; SURVIVAL ANALYSIS;

EID: 84912098360     PISSN: 15258610     EISSN: 15389375     Source Type: Journal    
DOI: 10.1016/j.jamda.2014.09.007     Document Type: Review

References (81)

1. von Haehling S., Anker S.D. Cachexia vs obesity: Where is the real unmet clinical need?. JCachexia Sarcopenia Muscle 2013, 4:245-246.
2. Vaughan V.C., Martin P., Lewandowski P.A. Cancer cachexia: Impact, mechanisms and emerging treatments. JCachexia Sarcopenia Muscle 2013, 4:95-109.
3. von Haehling S., Anker S.D. Cachexia as a major underestimated and unmet medical need: Facts and numbers. JCachexia Sarcopenia Muscle 2010, 1:1-5.
4. Evans W.J., Morley J.E., Argilés J., et al. Cachexia: A new definition. Clin Nutr 2008, 27:793-799.
5. Farkas J., von Haehling S., Kalantar-Zadeh K., et al. Cachexia as a major public health problem: Frequent, costly, and deadly. JCachexia Sarcopenia Muscle 2013, 4:173-178.
6. Morley J.E., Abbatecola A.M., Argiles J.M., et al. Society on Sarcopenia, Cachexia and Wasting Disorders Trialist Workshop. Sarcopenia with limited mobility: An international consensus. JAm Med Dir Assoc 2011, 12:403-409.
7. von Haehling S., Morley J.E., Anker S.D. From muscle wasting to sarcopenia and myopenia: Update 2012. JCachexia Sarcopenia Muscle 2012, 3:213-217.
8. Alchin D.R. Sarcopenia: Describing rather than defining a condition. JCachexia Sarcopenia Muscle August 5, 2014, [Epub ahead of print]. 10.1007/s13539-014-0156-8.
9. Fearon K., Evans W.J., Anker S.D. Myopenia-a new universal term for muscle wasting. JCachexia Sarcopenia Muscle 2011, 2:1-3.
10. Anker S.D., Coats A.J., Morley J.E., et al. Muscle wasting disease: A proposal for a new disease classification. JCachexia Sarcopenia Muscle 2014, 5:1-3.
11. Sakuma K., Yamaguchi A. Sarcopenia and cachexia: The adaptations of negative regulators of skeletal muscle mass. JCachexia Sarcopenia Muscle 2012, 3:77-94.
12. Ormsbee M.J., Prado C.M., Ilich J.Z., et al. Osteosarcopenic obesity: The role of bone, muscle, and fat on health. Cachexia Sarcopenia Muscle 2014, 5:183-192.
13. Pedroso F.E., Spalding P.B., Cheung M.C., et al. Inflammation, organomegaly, and muscle wasting despite hyperphagia in a mouse model of burn cachexia. JCachexia Sarcopenia Muscle 2012, 3:199-211.
14. Ferraro E., Molinari F., Berghella L. Molecular control of neuromuscular junction development. JCachexia Sarcopenia Muscle 2012, 3:199-211.
15. Morley J.E., von Haehling S., Anker S.D. Are we closer to having drugs to treat muscle wasting disease?. JCachexia Sarcopenia Muscle 2014, 5:83-87.
16. Malafarina V., Uriz-Otano F., Iniesta R., Gil-Guerrero L. Effectiveness of nutritional supplementation on muscle mass in treatment of sarcopenia in old age: A systematic review. JAm Med Dir Assoc 2013, 14:10-17.
17. von Haehling S., Lainscak M., Springer J., Anker S.D. Cardiac cachexia: A systematic overview. Pharmacol Ther 2009, 121:227-252.
18. Busquets S., Toledo M., Orpí M., et al. Myostatin blockage using actRIIB antagonism in mice bearing the Lewis lung carcinoma results in the improvement of muscle wasting and physical performance. JCachexia Sarcopenia Muscle 2012, 3:37-43.
19. Mirza K.A., Pereira S.L., Edens N.K., Tisdale M.J. Attenuation of muscle wasting in murine C2/C12 myotubes by epigallocatechin-3-gallate. JCachexia Sarcopenia Muscle March 20, 2014, [Epub ahead of print]. 10.1007/s13539-014-0139-9.
20. Tschirner A., von Haehling S., Palus S., et al. Ursodeoxycholic acid treatment in a rat model of cancer cachexia. JCachexia Sarcopenia Muscle 2012, 3:31-36.
21. Der-Torossian H., Wysong A., Shadfar S., et al. Metabolic derangements in the gastrocnemius and the effect of Compound A therapy in a murine model of cancer cachexia. JCachexia Sarcopenia Muscle 2013, 4:145-155.
22. Solheim T.S., Fayers P.M., Fladvad T., et al. European Palliative Care Research Collaborative (EPCRC) and the European Pharmacogenetic Study (EPOS). Is there a genetic cause of appetite loss? An explorative study in 1,853 cancer patients. JCachexia Sarcopenia Muscle 2012, 3:191-198.
23. Tan C.R., Yaffee P.M., Jamil L.H., et al. Pancreatic cancer cachexia: A review of mechanisms and therapeutics. Front Physiol 2014, 5:88.
24. Tsai V.W., Husaini Y., Manandhar R., et al. Anorexia/cachexia of chronic diseases: A role for the TGF-β family cytokine MIC-1/GDF15. JCachexia Sarcopenia Muscle 2012, 3:239-243.
25. Soenen S., Chapman I.M. Body weight, anorexia, and undernutrition in older people. JAm Med Dir Assoc 2013, 14:642-648.
26. Argilés J.M., Anguera A., Stemmler B. Anew look at an old drug for the treatment of cancer cachexia: Megestrol acetate. Clin Nutr 2013, 32:319-324.
27. Wen H.S., Li X., Cao Y.Z., et al. Clinical studies on the treatment of cancer cachexia with megestrol acetate plus thalidomide. Chemotherapy 2012, 58:461-467.
28. Greig C.A., Johns N., Gray C., et al. Phase I/II trial of formoterol fumarate combined with megestrol acetate in cachectic patients with advanced malignancy. Support Care Cancer 2014, 22:1269-1275.
29. Silvério R., Laviano A., Rossi Fanelli F., Seelaender M. L-carnitine and cancer cachexia: Clinical and experimental aspects. JCachexia Sarcopenia Muscle 2011, 2:37-44.
30. 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, 31:176-182.
31. 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.
32. Cuvelier G.D., Baker T.J., Peddie E.F., et al. Arandomized, double-blind, placebo-controlled clinical trial of megestrol acetate as an appetite stimulant in children with weight loss due to cancer and/or cancer therapy. Pediatr Blood Cancer 2014, 61:672-679.
33. Raghavendra V., Kulkarni S.K. Melatonin reversal of DOI-induced hypophagia in rats: Possible mechanism by suppressing 5-HT(2A) receptor-mediated activation of HPA axis. Brain Res 2000, 860:112-118.
34. Del Fabbro F., 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. JClin Oncol 2013, 31:1271-1276.
35. Hong D.S., Hui D., Bruera E., et al. MABp1, a first-in-class true human antibody targeting IL-1α in refractory cancers: An open-label, phase 1 dose-escalation and expansion study. Lancet Oncol 2014, 15:656-666.
36. Eriksson T., Bjorkman S., Hoglund P. Clinical pharmacology of thalidomide. Eur J Clin Pharmacol 2001, 57:365-376.
37. Sampaio E.P., Kaplan G., Miranda A., et al. The influence of thalidomide on the clinical and immunologic manifestation of erythema nodosum leprosum. JInfect Dis 1993, 168:408-414.
38. Yennurajalingam S., Willey J.S., Palmer J.L., et al. The role of thalidomide and placebo for the treatment of cancer-related anorexia-cachexia symptoms: Results of a double-blind placebo-controlled randomized study. JPalliat Care 2012, 15:1059-1064.
39. Davis M., Lasheen W., Walsh D., et al. Aphase II dose titration study of thalidomide for cancer-associated anorexia. JPain Symptom Manage 2012, 43:78-86.
40. Mak R.H., Ikizler A.T., Kovesdy C.P., et al. Wasting in chronic kidney disease. JCachexia Sarcopenia Muscle 2011, 2:9-25.
41. Rattanasompattikul M., Molnar M.Z., Lee M.L., et al. Anti-inflammatory and anti-oxidative nutrition in hypoalbuminemic dialysis patients (AIONID) study: Results of the pilot-feasibility, double-blind, randomized, placebo-controlled trial. JCachexia Sarcopenia Muscle 2013, 4:247-257.
42. von Haehling Steinbeck L., Doehner W., et al. Muscle wasting in heart failure: An overview. Int J Biochem Cell Biol 2013, 45:2257-2265.
43. Jarkovska Z., Krsek M., Rosicka M., Marek J. Endocrine and metabolic activities of a recently isolated peptide hormone ghrelin, an endogenous ligand of the growth hormone secretagogue receptor. Endocr Regul 2004, 38:80-86.
44. Fanzani A., Conraads V.M., Penna F., Martinet W. Molecular and cellular mechanisms of skeletal muscle atrophy: An update. JCachexia Sarcopenia Muscle 2012, 3:163-179.
45. Akamizu T., Kangawa K. Ghrelin for cachexia. JCachexia Sarcopenia Muscle 2010, 1:169-176.
46. Wolf I., Sadetzki S., Kanety H., et al. Adiponectin, ghrelin, and leptin in cancer cachexia in breast and colon cancer patients. Cancer 2006, 106:966-973.
47. Norman K., Stobäus N., Reiß J., et al. Effect of sexual dimorphism on muscle strength in cachexia. JCachexia Sarcopenia Muscle 2012, 3:111-116.
48. Burney B.O., Garcia J.M. Hypogonadism in male cancer patients. JCachexia Sarcopenia Muscle 2012, 3:149-155.
49. Lenk K., Palus S., Schur R., et al. Effect of ghrelin and its analogues, BIM-28131 and BIM-28125, on the expression of myostatin in a rat heart failure model. JCachexia Sarcopenia Muscle 2013, 4:63-69.
50. Knops M., Werner C.G., Scherbakov N., et al. Investigation of changes in body composition, metabolic profile and skeletal muscle functional capacity in ischemic stroke patients: The rationale and design of the Body Size in Stroke Study (BoSSS). JCachexia Sarcopenia Muscle 2013, 4:199-207.
51. Legakis I., Stathopoulos J., Matzouridis T., Stathopoulos G.P. Decreased plasma ghrelin levels in patients with advanced cancer and weight loss in comparison to healthy individuals. Anticancer Res 2009, 29:3949-3952.
52. Barao K., Silva T.D., Osorio G.A., et al. The behaviour of the peptides leptin and ghrelin, PYY, NPY, CART and MSH in gastric cancer patients. JCachexia Sarcopenia Muscle 2012, 3:281-301.
53. Coats A.J. Research on cachexia, sarcopenia and skeletal muscle in cardiology. JCachexia Sarcopenia Muscle 2012, 3:219-223.
54. Nagaya N., Moriya J., Yasumura Y., et al. Effects of ghrelin administration on left ventricular function, exercise capacity, and muscle wasting in patients with chronic heart failure. Circulation 2004, 110:3674-3679.
55. Nagaya N., Itoh T., Murakami S., et al. Treatment of cachexia with ghrelin in patients with COPD. Chest 2005, 128:1187-1193.
56. Garcia J.M., Graham C., Kumor K.W.P. Aphase II, randomized, placebo-controlled, double blind study of the efficacy and safety of RC-1291 for the treatment of cancer-cachexia [abstract]. JClin Oncol 2007, 25:S25.
57. Neary N.M., Small C.J., Wren A.M., et al. Ghrelin increases energy intake in cancer patients with impaired appetite: Acute, randomized, placebo-controlled trial. JClin Endocrinol Metab 2004, 89:2832-2836.
58. Strasser F., Lutz T.A., Maeder M.T., 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, 98:300-308.
59. Wynne K., Giannitsopoulou K., Small C.J., et al. Subcutaneous ghrelin enhances acute food intake in malnourished patients who receive maintenance peritoneal dialysis: a randomized, placebo-controlled trial. JAm Soc Nephrol 2005, 16:2111-2118.
60. Ashby D.R., Ford H.E., Wynne K.J., et al. Sustained appetite improvement in malnourished dialysis patients by daily ghrelin treatment. Kidney Int 2009, 76:199-206.
61. Miki K., Maekura R., Nagaya N., et al. Ghrelin treatment of cachectic patients with chronic obstructive pulmonary disease: A multicenter, randomized, double-blind, placebo-controlled trial. PLoS One 2012, 7:e35708.
62. Temel J., Bondarde S., Jain M., et al. Efficacy and safety results from a phase II study of anamorelin HCl, a ghrelin receptor agonist, in NSCLC patients. JCachexia Sarcopenia Muscle 2013, 4:295-343. (Abstract 5-01).
63. Abernethy A., Temel J., Currow D., et al. Anamorelin HCl for the treatment of anorexia-cachexia in lung cancer: Study design and baseline characteristics of patients in the phase III clinical trial ROMANA 2 (HT-ANAM-302). JCachexia Sarcopenia Muscle 2013, 4:295-343. (Abstract 5-02).
64. Garcia J.M., 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, 21:129-137.
65. Caminiti G., Volterrani M., Iellamo F., et al. Effect of long-acting testosterone treatment on functional exercise capacity, skeletal muscle performance, insulin resistance, and baroreflex sensitivity in elderly patients with chronic heart failure: A double-blind, placebo-controlled, randomized study. JAm Coll Cardiol 2009, 54:919-927.
66. Iellamo F., Volterrani M., Caminiti G., et al. Testosterone therapy in women with chronic heart failure: A pilot double-blind, randomized, placebo-controlled study. JAm Coll Cardiol 2010, 56:1310-1316.
67. Fülster S., Tacke M., Sandek A., et al. Muscle wasting in patients with chronic heart failure: Results from the studies investigating co-morbidities aggravating heart failure (SICA-HF). Eur Heart J 2013, 34:512-519.
68. Anker S.D., Chua T.P., Ponikowski P., et al. Hormonal changes and catabolic/anabolic imbalance in chronic heart failure and their importance for cardiac cachexia. Circulation 1997, 96:526-534.
69. Jankowska E.A., Rozentryt P., Ponikowska B., et al. Circulating estradiol and mortality in men with systolic chronic heart failure. JAMA 2009, 301:1892-1901.
70. Ebner N., Werner C.G., Doehner W., et al. Recent developments in the treatment of cachexia: Highlights from the 6th Cachexia Conference. JCachexia Sarcopenia Muscle 2012, 3:45-50.
71. Ebner N., Springer J., Kalantar-Zadeh K., et al. Mechanism and novel therapeutic approaches to wasting in chronic disease. Maturitas 2013, 75:199-206.
72. Dalton J.T., Barnette K.G., Bohl C.E., et al. The selective androgen receptor modulator GTx-024 (enobosarm) improves lean body mass and physical function in healthy elderly men and postmenopausal women: Results of a double-blind, placebo-controlled phase II trial. JCachexia Sarcopenia Muscle 2011, 2:153-161.
73. Nedergaard A., Sun S., Karsdal M.A., et al. Type VI collagen turnover-related peptides-novel serological biomarkers of muscle mass and anabolic response to loading in young men. JCachexia Sarcopenia Muscle 2013, 4:267-275.
74. Dobs A.S., Boccia R.V., Croot C.C., 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, 14:335-345.
75. Crawford J., Dalton J.T., Hancock M.L., et al. Enobosarm, a selective androgen receptor modulator (SARM), increases lean body mass (LBM) in advanced non-small cell lung cancer patients in two pivotal, international Phase 3 trials. JCachexia Sarcopenia Muscle 2014, 5:35-78. (Abstract 5-15).
76. Del Fabbro E., Garcia J.M., Dev R., et al. Testosterone replacement for fatigue inhypogonadal ambulatory males with advanced cancer: A preliminary double-blind placebo-controlled trial. Support Care Cancer 2013, 21:2599-2607.
77. Stewart Coats A.J., Srinivasan V., Surendran J., et al. on behalf of the ACT-ONE Trial Investigators. The ACT-ONE trial, a multicentre, randomised, double-blind, placebo-controlled, dose-finding study of the anabolic/catabolic transforming agent, MT-102 in subjects with cachexia related to stage III and IV non-small cell lung cancer and colorectal cancer: Study design. JCachexia Sarcopenia Muscle 2011, 24:201-207.
78. Pötsch M.S., Tschirner A., Palus S., et al. The anabolic catabolic transforming agent (ACTA) espindolol increases muscle mass and decreases fat mass in old rats. JCachexia Sarcopenia Muscle 2014, 52:149-158.
79. Palus S., Hartmann K., Braun T., et al. Beta-blocker for the treatment of cancer cachexia: are they all equal?. JCachexia Sarcopenia Muscle 2014, 5:35-78. (Abstract 4-19).
80. Stewart Coats A.J., Fuang H.G., Prabhash K., et al. Espindolol for the treatment and prevention of cachexia in patients with stage III/IV non-small cell lung cancer or colorectal cancer (ACT-ONE): randomised, double-blind, placebo-controlled, international multi-centre phase II study. JCachexia Sarcopenia Muscle 2014, 5:35-78. for and on behalf of the ACT-ONE study group, (Abstract 5-19).
81. Ebner N., Steinbeck L., Doehner W., et al. Highlights from the 7th Cachexia Conference: Muscle wasting pathophysiological detection and novel treatment strategies. JCachexia Sarcopenia Muscle 2014, 5:27-34.