A new look at an old drug for the treatment of cancer cachexia: Megestrol acetate

Clinical Nutrition

Volumn 32, Issue 3, 2013, Pages 319-324

  Argilés, Josep M ^a   Anguera, Anna ^b   Stemmler, Britta ^c  

^a UNIVERSITY OF BARCELONA   (Spain)

^b SL   (Spain)

^c BSA   (Spain)

Author keywords

Cancer cachexia; Megestrol acetate; Skeletal muscle

Indexed keywords

DRONABINOL; MEDROXYPROGESTERONE; MEGESTROL ACETATE; MUSCLE PROTEIN; PLACEBO;

ACNE; ADRENAL INSUFFICIENCY; BODY COMPOSITION; BODY WEIGHT; CACHEXIA; CONFUSION; DIARRHEA; DIZZINESS; DRUG EFFICACY; DRUG FEVER; DRUG INDUCED HEADACHE; DYSPEPSIA; EDEMA; FLATULENCE; FOOD INTAKE; HIRSUTISM; HUMAN; HYPERGLYCEMIA; IMPOTENCE; INSOMNIA; MOLECULAR DYNAMICS; NONHUMAN; PATHOPHYSIOLOGY; PROTEIN METABOLISM; QUALITY OF LIFE; REVIEW; SKELETAL MUSCLE; TOTAL PARENTERAL NUTRITION; TREATMENT DURATION; TREATMENT OUTCOME;

ANIMALS; CACHEXIA; CLINICAL TRIALS AS TOPIC; DOSE-RESPONSE RELATIONSHIP, DRUG; HUMANS; INFLAMMATION; MEGESTROL ACETATE; MUSCLE PROTEINS; MUSCULAR ATROPHY; NEOPLASMS; WEIGHT LOSS;

EID: 84877111452     PISSN: 02615614     EISSN: 15321983     Source Type: Journal    
DOI: 10.1016/j.clnu.2013.01.004     Document Type: Review

References (55)

1. Evans W.J., Morley J.E., Argilés J.M., Bales C., Baracos V., Guttridge D., et al. Cachexia: a new definition. Clin Nutr 2008, 27:793-799.
2. Argilés J.M., Alvarez B., Lopez-Soriano F.J. The metabolic basis of cancer cachexia. Med Res Rev 1997, 17:477-498.
3. Warren S. The immediate cause of death in cancer. Am J Med Sci 1932, 184:610-613.
4. Dewys W.D., Begg C., Lavin P.T., Band P.R., Bennett J.M., Bertino J.R., et al. Prognostic effect of weight loss prior to chemotherapy in cancer patients. Eastern Cooperative Oncology Group. Am J Med 1980, 69:491-497.
5. Argilés J.M., Anker S.D., Evans W.J., Morley J.E., Fearon K.C., Strasser F., et al. Consensus on cachexia definitions. J Am Med Dir Assoc 2010, 11:229-230.
6. Muscaritoli M., Anker S.D., Argilés J.M., Aversa Z., Bauer J.M., Biolo G., et al. Consensus definition of sarcopenia, cachexia and pre-cachexia: joint document elaborated by Special Interest Groups (SIG) "cachexia-anorexia in chronic wasting diseases" and "nutrition in geriatrics" Clin Nutr 2010, 29:154-159.
7. Fearon K., Strasser F., Anker S.D., Bosaeus I., Bruera E., Fainsinger R.L., et al. Definition and classification of cancer cachexia: an international consensus. Lancet Oncol 2011, 12:489-495.
8. Ottery F.D. Definition of standardized nutritional assessment and interventional pathways in oncology. Nutrition 1996, 12(1 Suppl.):S15-S19.
9. Isenring E., Cross G., Daniels L., Kellett E., Koczwara B. Validity of the malnutrition screening tool as an effective predictor of nutritional risk in oncology outpatients receiving chemotherapy. Support Care Cancer 2006, 14:1152-1156.
10. Argilés J.M., López-Soriano F.J., Toledo M., Betancourt A., Serpe R., Busquets S. The cachexia score (CASCO): a new tool for staging cachectic cancer patients. J Cachexia Sarcopenia Muscle 2011, 2:87-93.
11. Argilés J.M., López-Soriano F.J., Busquets S. Novel approaches to the treatment of cachexia. Drug Discov Today 2008, 13:73-78.
12. Solheim T.S., Fayers P.M., Fladvad T., Tan B., Skorpen F., Fearon K., et al. Is there a genetic cause of appetite loss? An explorative study in 1853 cancer patients. J Cachexia Sarcopenia Muscle 2012, 95:979-990. On behalf of the European Palliative Care Research Collaborative (EPCRC) and the European Pharmacogenetic Study (EPOS).
13. Ng E.H., Lowry S.F. Nutritional support and cancer cachexia. Evolving concepts of mechanisms and adjunctive therapies. Hematol Oncol Clin North Am 1991, 5:161-184.
14. Argilés J.M., Busquets S., Toledo M., Lopez-Soriano F.J. The role of cytokines in cancer cachexia. Curr Opin Support Palliat Care 2009, 3:263-268.
15. Argilés J.M., Busquets S., Lopez Soriano F.J. The role of uncoupling proteins in pathophysiological states. Muscle plasticity - advances in physiological research 2009, 195-207. Research Signpost, Kerala India. J. Magalhaes, A. Ascensao (Eds.).
16. Busquets S., Almendro V., Barreiro E., Figueras M., Argilés J.M., López-Soriano F.J. Activation of UCPs gene expression in skeletal muscle can be independent on both circulating fatty acids and food intake. Involvement of ROS in a model of mouse cancer cachexia. FEBS Lett 2005, 31(579):717-722.
17. Ametller E., Busquets S., Fuster G., Figueras M.T., Fontes de Oliveira C.C., Sette A., et al. Effects of formoterol on muscle regeneration in cancer cachexia. Insciences J 2011, 1:1-17.
18. Argilés J.M., López-Soriano J., Busquets S., López-Soriano F.J. Journey from cachexia to obesity by TNF. FASEB J 1997, 10:743-751.
19. Yeh S.S., Lovitt S., Schuster M.W. Usage of megestrol acetate in the treatment of anorexia-cachexia syndrome in the elderly. J Nutr Health Aging 2009, 13:448-454.
20. De Conno F., Martini C., Zecca E., Balzarini A., Venturino P., Groff L., et al. Megestrol acetate for anorexia in patients with far-advanced cancer: a double-blind controlled clinical trial. Eur J Cancer 1998, 34:1705-1709.
21. Bruera E., Ernst S., Hagen N., Spachynski K., Belzile M., Hanson J., et al. Effectiveness of megestrol acetate in patients with advanced cancer: a randomized, double-blind, crossover study. Cancer Prev Control 1998, 2:74-78.
22. Loprinzi C.L., Michalak J.C., Schaid D.J., Mailliard J.A., Athmann L.M., Goldberg R.M., 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, 11:762-767.
23. Bruera E., Macmillan K., Kuehn N., Hanson J., MacDonald R.N. A controlled trial of megestrol acetate on appetite, caloric intake, nutritional status, and other symptoms in patients with advanced cancer. Cancer 1990, 66:1279-1282.
24. Von Roenn J.H. Randomized trials of megestrol acetate for AIDS-associated anorexia and cachexia. Oncology 1994, 51(Suppl. 1):19-24.
25. Feliu J., Gonzalez-Baron M. Usefulness of megestrol acetate in cancer cachexia and anorexia. Am J Clin Oncol 1992, 15:436-440.
26. McCarthy H.D., Crowder R.E., Dryden S., Williams G. Megestrol acetate stimulates food and water intake in the rat: effects on regional hypothalamic neuropeptide Y concentrations. Eur J Pharmacol 1994, 265:99-102.
27. Von Roenn J.H., Armstrong D., Kotler D.P., Cohn D.L., Klimas N.G., Tchekmedyian N.S., et al. Megestrol acetate in patients with AIDS-related cachexia. Ann Intern Med 1994, 121:393-399.
28. Loprinzi C.L., Schaid D.J., Dose A.M., Burnham N.L., Jensen M.D. Body-composition changes in patients who gain weight while receiving megestrol acetate. J Clin Oncol 1993, 11:152-154.
29. Strang P. The effect of megestrol acetate on anorexia, weight loss and cachexia in cancer and AIDS patients. Anticancer Res 1997, 17:657-662.
30. Loprinzi C.L., Kugler J.W., Sloan J.A., Mailliard J.A., Krook J.E., Wilwerding M.B., et al. Randomized comparison of megestrol acetate versus dexamethasone versus fluoxymesterone for the treatment of cancer anorexia/cachexia. J Clin Oncol 1999, 17:3299-3306.
31. Jatoi A., Rowland K., Loprinzi C.L., Sloan J.A., Dakhil S.R., MacDonald N., 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, 22:2469-2476. North Central Cancer Treatment Group.
32. Jatoi A., Windschitl H.E., Loprinzi C.L., Sloan J.A., Dakhil S.R., Mailliard J.A., et al. Dronabinol versus megestrol acetate versus combination therapy for cancer-associated anorexia: a North Central Cancer Treatment Group study. J Clin Oncol 2002, 20:567-573.
33. Pascual López A., Roqué i Figuls M., Urrútia Cuchi G., Berenstein E.G., Almenar Pasies B., Balcells Alegre M., et al. Systematic review of megestrol acetate in the treatment of anorexia-cachexia syndrome. J Pain Symptom Manage 2004, 27:360-369.
34. Leśniak W., Bała M., Jaeschke R., Krzakowski M. Effects of megestrol acetate in patients with cancer anorexia-cachexia syndrome: a systematic review and meta-analysis. Pol Arch Med Wewn 2008, 118:636-644.
35. Berenstein E.G., Ortiz Z. Megestrol acetate for the treatment of anorexia-cachexia syndrome. Cochrane Database Syst Rev 2005, CD004310.
36. McQuellon R.P., Moose D.B., Russell G.B., Case L.D., Greven K., Stevens M., et al. Supportive use of megestrol acetate (Megace) with head/neck and lung cancer patients receiving radiation therapy. Int J Radiat Oncol Biol Phys 2002, 52:1180-1185.
37. McMillan D.C., O'Gorman P., Fearon K.C., McArdle C.S. A pilot study of megestrol acetate and ibuprofen in the treatment of cachexia in gastrointestinal cancer patients. Br J Cancer 1997, 76:788-790.
38. Madeddu C., Dessì M., Panzone F., Serpe R., Antoni G., Cau M.C., 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.
39. Macciò A., Madeddu C., Gramignano G., Mulas C., Floris C., Sanna N., 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, 124:417-425.
40. Costa A.M., Spence K.T., Plata-Salamán C.R., French-Mullen J.M. Residual Ca2+ channel current modulation by megestrol acetate via a G-protein alpha s-subunit in rat hypothalamic neurones. J Physiol 1995, 487:291-303.
41. Mantovani G., Macciò A., Esu S., Lai P., Santona M.C., Massa E., et al. Medroxyprogesterone acetate reduces the in vitro production of cytokines and serotonin involved in anorexia/cachexia and emesis by peripheral blood mononuclear cells of cancer patients. Eur J Cancer 1997, 33:602-607.
42. Mantovani G., Macciò A., Lai P., Massa E., Santona M.C. Cytokine involvement in cancer anorexia/cachexia: role of megestrol acetate and medroxyprogesterone acetate on cytokine downregulation and improvement of clinical symptoms. Crit Rev Oncol 1998, 9:99-106.
43. Lambert C.P., Flynn M.G., Sullivan D.H., Evans W.J. Effects of megestrol acetate on circulating interleukin-15 and interleukin-18 concentrations in healthy elderly men. J Gerontol A Biol Sci Med Sci 2004, 59:855-858.
44. Quinn L.S., Anderson B.G., Strait-Bodey L., Stroud A.M., Argilés J.M. Oversecretion of interleukin-15 from skeletal muscle reduces adiposity. Am J Physiol Endocrinol Metab 2009, 296:E191-E202.
45. Hamburger A.W., Parnes H., Gordon G.B., Shantz L.M., O'Donnell K.A., Aisner J. Megestrol acetate-induced differentiation of 3T3-L1 adipocytes in vitro. Semin Oncol 1988, 15(Suppl. 1):76-78.
46. Busquets S., Serpe R., Sirisi S., Toledo M., Coutinho J., Martínez R., et al. Megestrol acetate: its impact on muscle protein metabolism supports its use in cancer cachexia. Clin Nutr 2010, 29:733-737.
47. Marmonti E., Toledo M., Massa D., Mola M., López Soriano F.J., Busquets S., et al. Megestrol acetate treatment influences tissue amino acid uptake and incorporation during cancer cachexia. e-Espen 2012, 7:135-138.
48. Busquets S., Alvarez B., Lopez-Soriano F.J., Argilés J.M. Branched-chain amino acids: a role in skeletal muscle proteolysis in catabolic states?. J Cell Physiol 2002, 191:283-289.
49. Gebbia V., Testa A., Gebbia N. Prospective randomised trial of two dose levels of megestrol acetate in the management of anorexia-cachexia syndrome in patients with metastatic cancer. Br J Cancer 1996, 73:1576-1580.
50. Vadell C., Seguí M.A., Giménez-Arnau J.M., Morales S., Cirera L., Bestit I., et al. Anticachectic efficacy of megestrol acetate at different doses and versus placebo in patients with neoplastic cachexia. Am J Clin Oncol 1998, 21:347-351.
51. Tomiska M., Tomiskova M., Salajka F., Adam Z., Vorlicek J. Palliative treatment of cancer anorexia with oral suspension of megestrol acetate. Neoplasma 2003, 50:227-233.
52. Gullet N.P., Hebbar G., Ziegler T.R. Update on clinical trials of growth factors and anabolic steroids in cachexia and wasting. Am J Clin Nutr 2010, 91:1143-1147. S.
53. Koller E., Gibert C., Green L., Mann M., Bernstein B. Thrombotic events associated with megestrol acetate in patients with AIDS cachexia. Nutrition 1999, 15:294-298.
54. Sullivan D.H., Roberson P.K., Smith E.S., Price J.A., Bopp M.M. Effects of muscle strength training and megestrol acetate on strength, muscle mass and function in frail older people. J Am Geriatr Soc 2007, 55:20-28.
55. Argilés J.M., Olivan M., Busquets S., López-Soriano F.J. Optimal management of cancer anorexia-cachexia syndrome. Cancer Manag Res 2010, 2:27-38.