title: Megestrol acetate for treatment of anorexia-cachexia syndrome.
abstract: BACKGROUND
  This is an updated version of a previously published review in The Cochrane Library (2005, Issue 2) on 'Megestrol acetate for the treatment of anorexia-cachexia syndrome'. Megestrol acetate (MA) is currently used to improve appetite and to increase weight in cancer-associated anorexia. In 1993, MA was approved by the US Food and Drug Administration for the treatment of anorexia, cachexia or unexplained weight loss in patients with AIDS. The mechanism by which MA increases appetite is unknown and its effectiveness for anorexia and cachexia in neoplastic and AIDS (acquired immunodeficiency syndrome) patients is under investigation.
  
  
  OBJECTIVE
  To evaluate the efficacy, effectiveness and safety of MA in palliating anorexia-cachexia syndrome in patients with cancer, AIDS and other underlying pathologies.
  
  
  METHODS
  We sought studies through an extensive search of electronic databases, journals, reference lists, contact with investigators and other search strategies outlined in the methods. The most recent search for this update was carried out in May 2012.
  
  
  METHODS
  Studies were included in the review if they assessed MA compared to placebo or other drug treatments in randomised controlled trials of patients with a clinical diagnosis of anorexia-cachexia syndrome related to cancer, AIDS or any other underlying pathology.
  
  
  METHODS
  Two independent review authors conducted data extraction and evaluated methodological quality. We performed quantitative analyses using appetite and quality of life as a dichotomous variable, and analysed weight gain as continuous and dichotomous variables.
  
  
  RESULTS
  We included 35 trials in this update, the same number but not the same trials as in the previous version of the review. The trials comprised 3963 patients for effectiveness and 3180 for safety. Sixteen trials compared MA at different doses with placebo, seven trials compared different doses of MA with other drug treatments and 10 trials compared different doses of MA. Meta-analysis showed a benefit of MA compared with placebo, particularly with regard to appetite improvement and weight gain in cancer, AIDS and other underlying conditions, and lack of benefit in the same patients when MA was compared to other drugs. There was insufficient information to define the optimal dose of MA, but higher doses were more related to weight improvement than lower doses. Quality of life improvement in patients was seen only when comparing MA versus placebo but not other drugs in both subcategories: cancer and AIDS. Oedema, thromboembolic phenomena and deaths were more frequent in the patients treated with MA. More than 40 side effects were studied.
  
  
  CONCLUSIONS
  This review shows that MA improves appetite and is associated with slight weight gain in cancer, AIDS and in patients with other underlying pathology. Despite the fact that these patients are receiving palliative care they should be informed of the risks involved in taking MA.
authors.affiliation: Unidad de Hospitalización a Domicilio & CASP Spain, Hospital Universitari i Politècnic La Fe, Valencia, Spain. vicenteruizgarcia@gmail.com.
authors.forename: Vicente
authors.initials: V
authors.lastname: Ruiz Garcia
authors.forename: Eduardo
authors.initials: E
authors.lastname: López-Briz
authors.forename: Rafael
authors.initials: R
authors.lastname: Carbonell Sanchis
authors.forename: Jose Luis
authors.initials: JL
authors.lastname: Gonzalvez Perales
authors.forename: Sylvia
authors.initials: S
authors.lastname: Bort-Marti
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000150:complications; D000855:Anorexia / Q000188:drug therapy* / Q000209:etiology; D019167:Appetite Stimulants / Q000009:adverse effects / Q000627:therapeutic use*; D002100:Cachexia / Q000188:drug therapy* / Q000209:etiology; D006801:Humans; D019290:Megestrol Acetate / Q000009:adverse effects / Q000627:therapeutic use*; D009369:Neoplasms / Q000150:complications; D016032:Randomized Controlled Trials as Topic; D013577:Syndrome
chemical_list: D019167:Appetite Stimulants; D019290:Megestrol Acetate
references.citation: Rev Med Interne. 1996;17(1):79-84
references.pmid: 8677390
references.citation: Ann Pharmacother. 1994 May;28(5):595-7
references.pmid: 8068997
references.citation: Ann Pharmacother. 2005 Dec;39(12):2046-55
references.pmid: 16278256
references.citation: Therapie. 1999 Jul Aug;54(4):405-11
references.pmid: 10667106
references.citation: Ann Intern Med. 1994 Sep 15;121(6):400-8
references.pmid: 8053613
references.citation: J Clin Oncol. 2005 Nov 20;23(33):8500-11
references.pmid: 16293879
references.citation: J Clin Oncol. 1996 Jan;14(1):135-41
references.pmid: 8558188
references.citation: J Ren Nutr. 2010 Jan;20(1):52-62
references.pmid: 19819724
references.citation: Drugs. 2001;61(4):499-514
references.pmid: 11324680
references.citation: J Acquir Immune Defic Syndr. 2005 Sep 1;40(1):70-6
references.pmid: 16123685
references.citation: Lancet Oncol. 2011 May;12(5):489-95
references.pmid: 21296615
references.citation: Curr Treat Options Oncol. 2010 Dec;11(3-4):107-17
references.pmid: 21128029
references.citation: Semin Oncol. 1991 Feb;18(1 Suppl 2):32-4
references.pmid: 1992534
references.citation: J Am Geriatr Soc. 2007 Jan;55(1):20-8
references.pmid: 17233681
references.citation: Oncology (Williston Park). 1990 May;4(5):185-92; discussion 194
references.pmid: 2143402
references.citation: Kidney Int. 2006 Aug;70(3):417-22
references.pmid: 16775598
references.citation: Neoplasma. 2003;50(3):227-33
references.pmid: 12937858
references.citation: Clin Sci (Lond). 1997 Feb;92(2):215-21
references.pmid: 9059324
references.citation: J Pain Symptom Manage. 2004 Apr;27(4):360-9
references.pmid: 15050664
references.citation: J Gerontol A Biol Sci Med Sci. 2001 Jan;56(1):M48-54
references.pmid: 11193233
references.citation: Oncologist. 2010;15(2):200-11
references.pmid: 20156909
references.citation: Pharmacol Ther. 2009 Mar;121(3):227-52
references.pmid: 19061914
references.citation: Nutr Clin Pract. 2006 Feb;21(1):82-7
references.pmid: 16439773
references.citation: Ann Oncol. 1992 Aug;3 Suppl 3:25-7
references.pmid: 1382553
references.citation: Cancer Surv. 1994;21:99-115
references.pmid: 8565002
references.citation: Int J Androl. 2001 Aug;24(4):232-40
references.pmid: 11454075
references.citation: Control Clin Trials. 1996 Feb;17(1):1-12
references.pmid: 8721797
references.citation: Cancer. 1992 Mar 1;69(5):1268-74
references.pmid: 1739926
references.citation: Crit Rev Oncog. 1998;9(2):99-106
references.pmid: 9973244
references.citation: J Am Med Dir Assoc. 2007 Jul;8(6):363-77
references.pmid: 17619035
references.citation: Cancer. 2006 Feb 15;106(4):966-73
references.pmid: 16411208
references.citation: Drug Discov Today. 2008 Jan;13(1-2):73-8
references.pmid: 18190867
references.citation: Bull Cancer. 2000 Apr;87(4):315-28
references.pmid: 10827350
references.citation: Br J Cancer. 1999 Sep;81(1):80-6
references.pmid: 10487616
references.citation: J Clin Oncol. 1999 Oct;17(10):3299-306
references.pmid: 10506633
references.citation: J Ren Nutr. 2009 Jan;19(1):2-9
references.pmid: 19121762
references.citation: Cancer Manag Res. 2010 Jan 22;2:27-38
references.pmid: 21188094
references.citation: J Clin Oncol. 1990 Nov;8(11):1797-805
references.pmid: 2230868
references.citation: J Nutr Health Aging. 2002 May;6(3):191-200
references.pmid: 12152625
references.citation: Semin Oncol. 1986 Dec;13(4 Suppl 4):20-5
references.pmid: 3798125
references.citation: Int J STD AIDS. 1992 Jul-Aug;3(4):278-80
references.pmid: 1504160
references.citation: Ann Oncol. 2001 Mar;12(3):289-300
references.pmid: 11332139
references.citation: Am J Hosp Palliat Care. 2002 May-Jun;19(3):206-10
references.pmid: 12026045
references.citation: BMJ. 2010 Jul 16;341:c3515
references.pmid: 20639294
references.citation: Anticancer Res. 2001 Jul-Aug;21(4B):2941-7
references.pmid: 11712791
references.citation: Curr Probl Cancer. 2011 Mar-Apr;35(2):58-90
references.pmid: 21420558
references.citation: Clin Infect Dis. 2005 Oct 15;41(8):1179-85
references.pmid: 16163638
references.citation: CA Cancer J Clin. 2002 Mar-Apr;52(2):72-91
references.pmid: 11929007
references.citation: Int J Radiat Oncol Biol Phys. 2002 Apr 1;52(5):1180-5
references.pmid: 11955728
references.citation: Expert Opin Pharmacother. 2001 Nov;2(11):1825-38
references.pmid: 11825320
references.citation: Control Clin Trials. 1990 Dec;11(6):405-19
references.pmid: 1963133
references.citation: Pharmacotherapy. 2009 Apr;29(4):383-97
references.pmid: 19323618
references.citation: J Am Geriatr Soc. 2012 Apr;60(4):616-31
references.pmid: 22376048
references.citation: Oncology (Williston Park). 1989 Aug;3(8 Suppl):17-23
references.pmid: 2701575
references.citation: Eur J Cancer. 1999 Apr;35(4):586-95
references.pmid: 10492632
references.citation: J Clin Oncol. 2004 Jun 15;22(12):2469-76
references.pmid: 15197210
references.citation: Support Care Cancer. 2010 Aug;18(8):951-6
references.pmid: 19756773
references.citation: N Engl J Med. 1988 Jun 30;318(26):1728-33
references.pmid: 3374545
references.citation: Oncology. 1992;49 Suppl 2:46-9
references.pmid: 1461628
references.citation: Physiol Rev. 2009 Apr;89(2):381-410
references.pmid: 19342610
references.citation: J Natl Cancer Inst. 1990 Jul 4;82(13):1127-32
references.pmid: 2193166
references.citation: Clin Nutr. 2012 Apr;31(2):176-82
references.pmid: 22047681
references.citation: J Pain Symptom Manage. 1994 May;9(4):265-8
references.pmid: 8089543
references.citation: Semin Oncol. 1990 Dec;17(6 Suppl 9):17-33
references.pmid: 2259924
references.citation: Int J Cardiol. 2002 Sep;85(1):73-81
references.pmid: 12163211
references.citation: Adv Perit Dial. 2004;20:209-12
references.pmid: 15384828
references.citation: Ann Oncol. 1997 Mar;8(3):277-83
references.pmid: 9137798
references.citation: J Clin Endocrinol Metab. 2007 Feb;92(2):563-70
references.pmid: 17090640
references.citation: J Exp Clin Cancer Res. 2000 Dec;19(4):431-9
references.pmid: 11277319
references.citation: Clin Nutr. 2006 Oct;25(5):711-5
references.pmid: 16867306
references.citation: Eur J Cancer. 1997 Jan;33(1):75-9
references.pmid: 9071903
references.citation: Mayo Clin Proc. 2007 Sep;82(9):1131-40
references.pmid: 17803883
references.citation: Clin Geriatr Med. 2002 Nov;18(4):853-66
references.pmid: 12608509
references.citation: Am J Clin Oncol. 1992 Oct;15(5):436-40
references.pmid: 1524045
references.citation: Semin Oncol. 1990 Dec;17(6 Suppl 9):8-12
references.pmid: 2259930
references.citation: AIDS Patient Care STDS. 1999 Mar;13(3):149-52
references.pmid: 10375262
references.citation: J Clin Oncol. 1993 Apr;11(4):762-7
references.pmid: 8478668
references.citation: Semin Oncol. 1991 Feb;18(1 Suppl 2):35-42
references.pmid: 1992535
references.citation: Vnitr Lek. 1997 Apr;43(4):250-5
references.pmid: 9601846
references.citation: Clin Infect Dis. 2004 Mar 15;38(6):895-902
references.pmid: 14999637
references.citation: Strahlenther Onkol. 1996 Mar;172(3):162-8
references.pmid: 8721265
references.citation: J Am Geriatr Soc. 2006 Jan;54(1):172-3; author reply 173-4
references.pmid: 16420220
references.citation: Oncology. 1994 Oct;51 Suppl 1:19-24
references.pmid: 7970504
references.citation: Cochrane Database Syst Rev. 2005 Apr 18;(2):CD004310
references.pmid: 15846706
references.citation: Oncology (Williston Park). 1996 Jul;10(7):1049-56; discussion 1062-4, 1067-8
references.pmid: 8837121
references.citation: J Head Trauma Rehabil. 2000 Jun;15(3):962-4
references.pmid: 10785626
references.citation: Tumori. 2002 Jul-Aug;88(4):277-80
references.pmid: 12400976
references.citation: Br J Cancer. 1999 Feb;79(3-4):495-500
references.pmid: 10027319
references.citation: J Clin Oncol. 1993 Jan;11(1):152-4
references.pmid: 8418227
references.citation: Nutr Clin Pract. 2006 Apr;21(2):168-74
references.pmid: 16556927
references.citation: Acta Oncol. 1993;32(1):37-41
references.pmid: 8466763
references.citation: Am J Med Sci. 1952 May;223(5):469-78
references.pmid: 14923654
references.citation: J Am Med Dir Assoc. 2004 Jan-Feb;5(1):24-30
references.pmid: 14706125
references.citation: Oncology. 1992;49 Suppl 2:32-4
references.pmid: 1461625
references.citation: Support Care Cancer. 2010 Jun;18(6):667-77
references.pmid: 19582484
references.citation: Med Res Rev. 2001 Jan;21(1):83-101
references.pmid: 11135301
references.citation: Curr Opin Oncol. 1993 Jul;5(4):633-8
references.pmid: 8364079
references.citation: Pol Arch Med Wewn. 2008 Nov;118(11):636-44
references.pmid: 19140567
references.citation: Am J Clin Oncol. 1998 Aug;21(4):347-51
references.pmid: 9708631
references.citation: Oncology. 1992;49 Suppl 2:43-5
references.pmid: 1461627
references.citation: Support Care Cancer. 1995 Mar;3(2):120-2
references.pmid: 7773579
references.citation: Nutr Hosp. 2006 May;21 Suppl 3:17-26
references.pmid: 16768027
references.citation: Int J Nanomedicine. 2006;1(4):411-6
references.pmid: 17722275
references.citation: Int J Cardiol. 2009 Mar 6;132(3):432-3; author reply 434
references.pmid: 17651825
references.citation: Cancer Prev Control. 1998 Apr;2(2):74-8
references.pmid: 9765767
references.citation: Semin Oncol. 1988 Apr;15(2 Suppl 1):68-75
references.pmid: 3285486
references.citation: Med Clin (Barc). 2002 Jul 6;119(5):166-70
references.pmid: 12200017
references.citation: Clin Nutr. 1994 Apr;13(2):85-9
references.pmid: 16843365
references.citation: J Clin Oncol. 1998 Oct;16(10):3439-60
references.pmid: 9779724
references.citation: Chest. 2002 Apr;121(4):1070-8
references.pmid: 11948034
references.citation: J Clin Oncol. 2002 Jan 15;20(2):567-73
references.pmid: 11786587
references.citation: JAMA. 1991 Jul 3;266(1):93-8
references.pmid: 2046134
references.citation: Eur J Cancer. 1998 Oct;34(11):1705-9
references.pmid: 9893656
references.citation: Oncology. 1992;49 Suppl 2:35-42
references.pmid: 1461626
references.citation: Oncology. 1994 Oct;51 Suppl 1:2-7
references.pmid: 7970505
references.citation: Rev Clin Esp. 2004 Oct;204(10):542-4
references.pmid: 15456608
references.citation: Nutr Hosp. 1998 Mar-Apr;13(2):69-75
references.pmid: 9644944
references.citation: Cancer Treat Rev. 1989 Mar;16(1):49-63
references.pmid: 2471590
references.citation: Am J Cardiol. 2008 Jun 2;101(11A):89E-103E
references.pmid: 18514634
references.citation: J Support Oncol. 2006 Nov-Dec;4(10):506-7
references.pmid: 17136865
references.citation: Curr Opin Clin Nutr Metab Care. 2001 May;4(3):179-82
references.pmid: 11517349
references.citation: AIDS Res Hum Retroviruses. 1997 Mar 1;13(4):305-15
references.pmid: 9071430
references.citation: J Pediatr. 2002 Apr;140(4):439-44
references.pmid: 12006958
references.citation: Lijec Vjesn. 2007 Dec;129(12):381-6
references.pmid: 18383739
references.citation: J Clin Oncol. 2003 Oct 1;21(19):3665-75
references.pmid: 14512399
references.citation: Ann Intern Med. 2001 Dec 4;135(11):982-9
references.pmid: 11730399
references.citation: Med Clin (Barc). 2011 Jul 23;137(5):193-8
references.pmid: 21524765
references.citation: J Pediatr Gastroenterol Nutr. 2000 Sep;31(3):264-9
references.pmid: 10997370
references.citation: Expert Opin Emerg Drugs. 2007 Nov;12(4):555-70
references.pmid: 17979599
references.citation: Stat Med. 1999 Oct 30;18(20):2693-708
references.pmid: 10521860
references.citation: Oncologist. 2007;12 Suppl 1:43-51
references.pmid: 17573455
references.citation: J Am Geriatr Soc. 2000 May;48(5):485-92
references.pmid: 10811540
references.citation: J Nutr Health Aging. 2009 May;13(5):448-54
references.pmid: 19390752
references.citation: Am Fam Physician. 2001 Sep 1;64(5):807-14
references.pmid: 11563572
references.citation: Cancer. 1990 Sep 15;66(6):1279-82
references.pmid: 2205358
references.citation: Anticancer Drugs. 1993 Apr;4(2):115-25
references.pmid: 8490191
references.citation: Br J Cancer. 1996 Jun;73(12):1576-80
references.pmid: 8664133
references.citation: Ann Pharmacother. 1998 Apr;32(4):446-58
references.pmid: 9562141
references.citation: Nutr Clin Pract. 1993 Jun;8(3):115-8
references.pmid: 8289758
references.citation: Clin Infect Dis. 2006 Mar 15;42(6):836-42
references.pmid: 16477562
references.citation: J Am Geriatr Soc. 2005 Jun;53(6):970-5
references.pmid: 15935019
references.citation: Prim Care. 2011 Jun;38(2):225-46, viii
references.pmid: 21628036
references.citation: J Am Geriatr Soc. 2004 Oct;52(10):1708-12
references.pmid: 15450049
references.citation: Curr Opin Nephrol Hypertens. 2007 Nov;16(6):542-6
references.pmid: 18089968
references.citation: Support Care Cancer. 1998 Mar;6(2):109-13
references.pmid: 9540168
references.citation: Nutrition. 1996 Jan;12(1 Suppl):S43-7
references.pmid: 8850220
references.citation: Radiother Oncol. 1997 Apr;43(1):75-9
references.pmid: 9165140
references.citation: Expert Opin Pharmacother. 2007 Jun;8(8):1085-90
references.pmid: 17516872
references.citation: Ann Intern Med. 1994 Sep 15;121(6):393-9
references.pmid: 7794302
references.citation: Oncology (Williston Park). 1994 Mar;8(3):43-9; discussion 49-50, 52
references.pmid: 7517169
references.citation: J Ren Nutr. 2009 Mar;19(2):167-71
references.pmid: 19218044
references.citation: Surg Gynecol Obstet. 1982 Dec;155(6):888-90
references.pmid: 7147170
references.citation: J Chemother. 2003 Jun;15(3):220-5
references.pmid: 12868546
references.citation: Semin Oncol. 1990 Dec;17(6 Suppl 9):63-7
references.pmid: 2259928
references.citation: J Am Geriatr Soc. 2011 Mar;59(3):463-72
references.pmid: 21391936
references.citation: J Clin Oncol. 1994 Jan;12(1):213-25
references.pmid: 8270980
references.citation: Drugs. 1992 Apr;43(4):499-506
references.pmid: 1377116
references.citation: Nutrition. 2008 Apr;24(4):305-13
references.pmid: 18262758