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Reviews

Phase II drugs that are currently in development for the treatment of cachexia

, MD PhD, , MD, , PhD & , PhD

Bibliography

  • Fearon K, Strasser F, Anker SD, et al. Definition and classification of cancer cachexia: an international consensus. Lancet Oncol 2011;12(5):489-95
  • Evans WJ, Morley JE, Argiles J, et al. Cachexia: a new definition. Clin Nutr 2008;27(6):793-9
  • Schols AM. Nutrition as a metabolic modulator in COPD. Chest 2013;144(4):1340-5
  • Aapro M, Arends J, Bozzetti F, et al. Early recognition of malnutrition and cachexia in the cancer patient: a position paper of a european school of oncology task force. Ann Oncol 2014. [Epub ahead of print]
  • Pausch T, Hartwig W, Hinz U, et al. Cachexia but not obesity worsens the postoperative outcome after pancreatoduodenectomy in pancreatic cancer. Surgery 2012;152(3 Suppl 1):S81-8
  • Prado CM, Baracos VE, McCargar LJ, et al. Body composition as an independent determinant of 5-fluorouracil-based chemotherapy toxicity. Clin Cancer Res 2007;13(11):3264-8
  • Prado CM, Lieffers JR, McCargar LJ, et al. Prevalence and clinical implications of sarcopenic obesity in patients with solid tumours of the respiratory and gastrointestinal tracts: a population-based study. Lancet Oncol 2008;9(7):629-35
  • Langen RC, Gosker HR, Remels AH, Schols AM. Triggers and mechanisms of skeletal muscle wasting in chronic obstructive pulmonary disease. Int J Biochem Cell Biol 2013;45(10):2245-56
  • von Haehling S, Steinbeck L, Doehner W, et al. Muscle wasting in heart failure: an overview. Int J Biochem Cell Biol 2013;45(10):2257-65
  • Amitani M, Asakawa A, Amitani H, Inui A. Control of food intake and muscle wasting in cachexia. Int J Biochem Cell Biol 2013;45(10):2179-85
  • Sandri M. Protein breakdown in muscle wasting: role of autophagy-lysosome and ubiquitin-proteasome. Int J Biochem Cell Biol 2013;45(10):2121-9
  • Fearon KC, Glass DJ, Guttridge DC. Cancer cachexia: mediators, signaling, and metabolic pathways. Cell Metab 2012;16(2):153-66
  • Op den Kamp CM, Langen RC, Snepvangers FJ, et al. Nuclear transcription factor kappa b activation and protein turnover adaptations in skeletal muscle of patients with progressive stages of lung cancer cachexia. Am J Clin Nutr 2013;98(3):738-48
  • Op den Kamp CM, Langen RC, Minnaard R, et al. Pre-cachexia in patients with stages I-III non-small cell lung cancer: systemic inflammation and functional impairment without activation of skeletal muscle ubiquitin proteasome system. Lung Cancer 2012;76(1):112-17
  • Guo Y, Gosker HR, Schols AM, et al. Autophagy in locomotor muscles of patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2013;188(11):1313-20
  • Martinez-Outschoorn UE, Whitaker-Menezes D, Pavlides S, et al. The autophagic tumor stroma model of cancer or “battery-operated tumor growth”: a simple solution to the autophagy paradox. Cell Cycle 2010;9(21):4297-306
  • Todorov P, Cariuk P, McDevitt T, et al. Characterization of a cancer cachectic factor. Nature 1996;379(6567):739-42
  • Zhou X, Wang JL, Lu J, et al. Reversal of cancer cachexia and muscle wasting by actriib antagonism leads to prolonged survival. Cell 2010;142(4):531-43
  • Langen RC, Haegens A, Vernooy JH, et al. Nf-kappab activation is required for the transition of pulmonary inflammation to muscle atrophy. Am J Respir Cell Mol Biol 2012;47(3):288-97
  • Cai D, Frantz JD, Tawa NE Jr, et al. Ikkbeta/NF-kappaB activation causes severe muscle wasting in mice. Cell 2004;119(2):285-98
  • Creutzberg EC, Schols AM, Weling-Scheepers CA, et al. Characterization of nonresponse to high caloric oral nutritional therapy in depleted patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2000;161(3 Pt 1):745-52
  • Staal-van den Brekel AJ, Dentener MA, Schols AM, et al. Increased resting energy expenditure and weight loss are related to a systemic inflammatory response in lung cancer patients. J Clin Oncol 1995;13(10):2600-5
  • Schols AM, Soeters PB, Mostert R, et al. Energy balance in chronic obstructive pulmonary disease. Am Rev Respir Dis 1991;143(6):1248-52
  • Sanchez-Lara K, Arrieta O, Pasaye E, et al. Brain activity correlated with food preferences: a functional study comparing advanced non-small cell lung cancer patients with and without anorexia. Nutrition 2013;29(7-8):1013-19
  • Clinicaltrials.Gov. Available from: http://clinicaltrialsgov
  • Nederlands trial register. Available from: wwwtrialregisternl
  • International standard randomised controlled trial number register. Available from: http://wwwcontrolled-trialscom/isrctn/
  • Inui A. Feeding and body-weight regulation by hypothalamic neuropeptides–mediation of the actions of leptin. Trends Neurosci 1999;22(2):62-7
  • Berenstein G, Ortiz Z; Editorial Group: Cochrane Pain PaSCG. Megestrol acetate for treatment of anorexia-cachexia syndrome. Cochrane Libr 2005;2:1-36
  • Brown J. A systematic review of the evidence on symptom management of cancer-related anorexia and cachexia. Oncol Nurs Forum 2002;29(3):517-32
  • 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(33):8500-11
  • Dewys WD, Begg C, Lavin PT, et al. Prognostic effect of weight loss prior to chemotherapy in cancer patients. Am J Med 1980;69(4):491-7
  • Gullick HD. Carcinoma of the pancreas; a review and critical study of 100 cases. Medicine 1959;38(1):47-84
  • Matsumoto J, Traverso LW. Exocrine function following the whipple operation as assessed by stool elastase. J Gastrointest Surg 2006;10(9):1225-9
  • Sikkens ECM, Cahen DL, de Wit J, et al. A prospective assessment of the natural course of the exocrine pancreatic function in patients with a pancreatic head tumor. J Clin Gastroenterol 2014;48(5):e43-6
  • Bruno MJ, Haverkort EB, Tijssen GP, et al. Placebo controlled trial of enteric coated pancreatin microsphere treatment in patients with unresectable cancer of the pancreatic head region. Gut 1998;42(1):92-6
  • Taylor JR, Gardner TB, Waljee AK, et al. Systematic review: efficacy and safety of pancreatic enzyme supplements for exocrine pancreatic insufficiency. Aliment Pharmacol Ther 2010;31(1):57-72
  • Gordon JN, Trebble TM, Ellis RD, et al. Thalidomide in the treatment of cancer cachexia: a randomised placebo controlled trial. Gut 2005;54(4):540-5
  • Reid J, Mills M, Cantwell M, et al. Thalidomide for managing cancer cachexia. Cochrane Database Syst Rev 2012;4:CD008664
  • Corral LG, Haslett PA, Muller GW, et al. Differential cytokine modulation and T cell activation by two distinct classes of thalidomide analogues that are potent inhibitors of TNF-alpha. J Immunol 1999;163(1):380-6
  • Bonetto A, Aydogdu T, Kunzevitzky N, et al. STAT3 activation in skeletal muscle links muscle wasting and the acute phase response in cancer cachexia. PLoS One 2011;6(7):e22538
  • Sharma RA, Steward WP, Daines CA, et al. Toxicity profile of the immunomodulatory thalidomide analogue, lenalidomide: phase I clinical trial of three dosing schedules in patients with solid malignancies. Eur J Cancer 2006;42(14):2318-25
  • Chasen M, Hirschman SZ, Bhargava R. Phase II study of the novel peptide-nucleic acid ohr118 in the management of cancer-related anorexia/cachexia. J Am Med Dir Assoc 2011;12(1):62-7
  • Chasen M, Bhargava R, Hirschman SZ, Taraporewala I. Abstracts of the 7th cachexia conference, kobe/osaka, Japan, december 9–11, 2013. J Cachexia Sarcopenia Muscle 2013;4(4):295-343
  • Thompson MG, Palmer RM. Signalling pathways regulating protein turnover in skeletal muscle. Cell Signal 1998;10(1):1-11
  • Smith KL, Tisdale MJ. Mechanism of muscle protein degradation in cancer cachexia. Br J Cancer 1993;68(2):314-18
  • Bondesen BA, Mills ST, Pavlath GK. The COX-2 pathway regulates growth of atrophied muscle via multiple mechanisms. Am J Physiol Cell Physiol 2006;290(6):C1651-9
  • Lai V, George J, Richey L, et al. Results of a pilot study of the effects of celecoxib on cancer cachexia in patients with cancer of the head, neck, and gastrointestinal tract. Head Neck 2008;30(1):67-74
  • McMillan DC, Wigmore SJ, Wigmore KCH, et al. A prospective randomized study of megestrol acetate and ibuprofen in gastrointestinal cancer patients with weight loss. Br J Cancer 1999;79(3-4):495-500
  • Mantovani G, Macciò A, Madeddu C, et al. Phase II nonrandomized study of the efficacy and safety of COX-2 inhibitor celecoxib on patients with cancer cachexia. J Mol Med 2010;88(1):85-92
  • Motsko S, Rascati K, Busti A, et al. Temporal relationship between use of NSAIDs, including selective COX-2 inhibitors, and cardiovascular risk. Drug Saf 2006;29(7):621-32
  • Bhattacharyya GS, Julka PK, Bondarde S, et al. Phase II study evaluating safety and efficacy of coadministering propranolol and etodolac for treating cancer cachexia. J Clin Oncol ASCO Meeting Abstracts 2010;28(15 Suppl):e18059
  • Glasner A, Avraham R, Rosenne E, et al. Improving survival rates in two models of spontaneous postoperative metastasis in mice by combined administration of a beta-adrenergic antagonist and a cyclooxygenase-2 inhibitor. J Immunol 2010;184(5):2449-57
  • Di Girolamo FG, Situlin R, Mazzucco S, et al. Omega-3 fatty acids and protein metabolism: enhancement of anabolic interventions for sarcopenia. Curr Opin Clin Nutr Metab Care 2014;17(2):145-50
  • Smith GI, Atherton P, Reeds DN, et al. Dietary omega-3 fatty acid supplementation increases the rate of muscle protein synthesis in older adults: a randomized controlled trial. Am J Clin Nutr 2011;93(2):402-12
  • Dewey A, Baughan C, Dean TP, 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
  • Murphy RA, Mourtzakis M, Chu QSC, 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(8):1775-82
  • van der Meij BS, Langius JAE, 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(10):1774-80
  • 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(7):1027-33
  • 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(10):1469-73
  • Sugawara K, Takahashi H, Kashiwagura T, et al. Effect of anti-inflammatory supplementation with whey peptide and exercise therapy in patients with COPD. Respir Med 2012;106(11):1526-34
  • Sugawara K, Takahashi H, Kasai C, et al. Effects of nutritional supplementation combined with low-intensity exercise in malnourished patients with COPD. Respir Med 2010;104(12):1883-9
  • Laviano A, Rianda S, Molfino A, Fanelli FR. Omega-3 fatty acids in cancer. Curr Opin Clin Nutr Metab Care 2013;16(2):156-61
  • Broekhuizen R, Wouters EF, Creutzberg EC, Schols AM. Raised CRP levels mark metabolic and functional impairment in advanced COPD. Thorax 2006;61(1):17-22
  • Kotwal S, Jun M, Sullivan D, et al. Omega 3 fatty acids and cardiovascular outcomes: systematic review and meta-analysis. Circ Cardiovasc Qual Outcomes 2012;5(6):808-18
  • Ali S, Chen JA, Garcia JM. Clinical development of ghrelin axis-derived molecules for cancer cachexia treatment. Curr Opin Support Palliat Care 2013;7(4):368-75
  • Porporato PE, Filigheddu N, Reano S, et al. Acylated and unacylated ghrelin impair skeletal muscle atrophy in mice. J Clin Invest 2013;123(2):611-22
  • Dickson SL, Egecioglu E, Landgren S, et al. The role of the central ghrelin system in reward from food and chemical drugs. Mol Cell Endocrinol 2011;340(1):80-7
  • Yasuda T, Masaki T, Kakuma T, Yoshimatsu H. Centrally administered ghrelin suppresses sympathetic nerve activity in brown adipose tissue of rats. Neurosci Lett 2003;349(2):75-8
  • Wren AM, Small CJ, Ward HL, et al. The novel hypothalamic peptide ghrelin stimulates food intake and growth hormone secretion. Endocrinology 2000;141(11):4325-8
  • 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(1):129-37
  • Broglio F, Boutignon F, Benso A, et al. Ep1572: a novel peptido-mimetic gh secretagogue with potent and selective GH-releasing activity in man. J Endocrinol Invest 2002;25(8):RC26-8
  • 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(2):300-8
  • 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(11):785-92
  • Stewart Coats A, Srinivasan V, Surendran J, et al. 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. J Cachexia Sarcopenia Muscle 2011;2(4):201-7
  • von Haehling S, Stepney R, Anker SD. Advances in understanding and treating cardiac cachexia: highlights from the 5th cachexia conference. Int J Cardiol 2010;144:347-9
  • Ebner N, Steinbeck L, Doehner W, et al. Highlights from the 7th cachexia conference: muscle wasting pathophysiological detection and novel treatment strategies. J Cachexia Sarcopenia Muscle 2014;5(1):27-34
  • Ma JD, Heavey SF, Revta C, Roeland EJ. Novel investigational biologics for the treatment of cancer cachexia. Expert Opin Biol Ther 2014. [Epub ahead of print]
  • Lach-Trifilieff E, Minetti GC, Sheppard K, et al. An antibody blocking activin type II receptors induces strong skeletal muscle hypertrophy and protects from atrophy. Mol Cell Biol 2014;34(4):606-18
  • Reichert JM. Antibodies to watch in 2014. mAbs 2013;6(1):5-14
  • Baracos VE, Reiman T, Mourtzakis M, et al. Body composition in patients with non-small cell lung cancer: a contemporary view of cancer cachexia with the use of computed tomography image analysis. Am J Clin Nutr 2010;91(4):1133S-7S
  • Bonetto A, Aydogdu T, Jin X, et al. JAK/STAT3 pathway inhibition blocks skeletal muscle wasting downstream of IL-6 and in experimental cancer cachexia. Am J Physiol Endocrinol Metab 2012;303(3):E410-21
  • Verstovsek S, Kantarjian H, Mesa RA, et al. Safety and efficacy of INCB018424, a JAK1 and JAK2 inhibitor, in myelofibrosis. N Engl J Med 2010;363(12):1117-27
  • Harrison C, Kiladjian J-J, Al-Ali HK, et al. JAK inhibition with ruxolitinib versus best available therapy for myelofibrosis. N Engl J Med 2012;366(9):787-98
  • Madeddu C, Maccio A, Mantovani G. Multitargeted treatment of cancer cachexia. Crit Rev Oncog 2012;17(3):305-14
  • Schols AM, Slangen J, Volovics L, Wouters EF. Weight loss is a reversible factor in the prognosis of chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1998;157(6 Pt 1):1791-7
  • Pison CM, Cano NJ, Cherion C, et al. Multimodal nutritional rehabilitation improves clinical outcomes of malnourished patients with chronic respiratory failure: a randomised controlled trial. Thorax 2011;66(11):953-60
  • Groen HJ, Sietsma H, Vincent A, et al. Randomized, placebo-controlled phase III study of docetaxel plus carboplatin with celecoxib and cyclooxygenase-2 expression as a biomarker for patients with advanced non-small-cell lung cancer: the NVALT-4 study. J Clin Oncol 2011;29(32):4320-6
  • Penna F, Costamagna D, Pin F, et al. Autophagic degradation contributes to muscle wasting in cancer cachexia. Am J Pathol 2013;182(4):1367-78
  • Doucet M, Russell AP, Leger B, et al. Muscle atrophy and hypertrophy signaling in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2007;176(3):261-9
  • Tsoli M, Schweiger M, Vanniasinghe AS, et al. Depletion of white adipose tissue in cancer cachexia syndrome is associated with inflammatory signaling and disrupted circadian regulation. PLoS One 2014;9(3):e92966
  • Tsoli M, Moore M, Burg D, et al. Activation of thermogenesis in brown adipose tissue and dysregulated lipid metabolism associated with cancer cachexia in mice. Cancer Res 2012;72(17):4372-82

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