Cancer cachexia: medical management.
BACKGROUND
Cachexia is a complex metabolic syndrome associated with many chronic or end-stage diseases, especially cancer, and is characterized by loss of muscle with or without loss of fat mass. The management of cachexia is a complex challenge that should address the different causes underlying this clinical event with an integrated or multimodal treatment approach targeting the different factors involved in its pathophysiology.


METHODS
The purpose of this article was to review the current medical treatment of cancer-related cachexia, in particular focusing on combination therapy and ongoing research.


RESULTS
Among the treatments proposed in the literature for cancer-related cachexia, some proved to be ineffective, namely, cyproheptadine, hydrazine, metoclopramide, and pentoxifylline. Among effective treatments, progestagens are currently considered the best available treatment option for cancer-related cachexia, and they are the only drugs approved in Europe. Drugs with a strong rationale that have failed or have not shown univocal results in clinical trials so far include eicosapentaenoic acid, cannabinoids, bortezomib, and anti-TNF-alpha MoAb. Several emerging drugs have shown promising results but are still under clinical investigation (thalidomide, selective cox-2 inhibitors, ghrelin mimetics, insulin, oxandrolone, and olanzapine).


CONCLUSIONS
To date, despite several years of co-ordinated efforts in basic and clinical research, practice guidelines for the prevention and treatment of cancer-related muscle wasting are lacking, mainly because of the multifactorial pathogenesis of the syndrome. From all the data presented, one can speculate that one single therapy may not be completely successful in the treatment of cachexia. From this point of view, treatments involving different combinations are more likely to be successful.
Mantovani
Giovanni
G
Department of Medical Oncology, University of Cagliari, Cagliari, Italy. mantovan@medicina.unica.it
Madeddu
Clelia
C
D002100:Cachexia / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D004359:Drug Therapy, Combination / Q000379:methods* / Q000639:trends; D006801:Humans; D009369:Neoplasms / Q000150:complications*
J Exp Ther Oncol. 2004 Apr;4(1):69-78
15255293
J Clin Oncol. 2006 Jul 20;24(21):3401-7
16849754
Clin Cancer Res. 2003 Oct 15;9(13):4653-65
14581334
Cancer. 1992 Mar 1;69(5):1268-74
1739926
Int J Clin Lab Res. 1995;25(3):135-41
8562975
Br J Cancer. 1994 May;69(5):826-32
8180010
Cancer Epidemiol Biomarkers Prev. 2006 May;15(5):1030-4
16702388
Cochrane Database Syst Rev. 2005 Apr 18;(2):CD004310
15846706
J Clin Endocrinol Metab. 2004 Jun;89(6):2832-6
15181065
Am J Pathol. 2005 Apr;166(4):1131-41
15793293
J Clin Oncol. 2002 Jan 15;20(2):567-73
11786587
BioDrugs. 2005;19(3):179-87
15984902
Nutr Cancer. 2007;59(1):14-20
17927497
Drugs. 2001;61(4):499-514
11324680
Nutrition. 2008 Sep;24(9):806-14
18725076
FEBS Lett. 2004 Jul 2;569(1-3):201-6
15225634
Support Care Cancer. 2008 Mar;16(3):229-34
18071761
Br Med J (Clin Res Ed). 1984 Jan 7;288(6410):27
6418303
Clin Cancer Res. 2007 May 1;13(9):2699-706
17473202
Curr Opin Oncol. 2006 Jul;18(4):335-40
16721127
Curr Opin Clin Nutr Metab Care. 2005 Jul;8(4):408-14
15930966
Mol Psychiatry. 2000 Nov;5(6):616-32
11126392
Free Radic Res. 2003 Feb;37(2):213-23
12653210
Drug Discov Today. 2008 Jan;13(1-2):73-8
18190867
Br J Cancer. 1999 Sep;81(1):80-6
10487616
J Clin Oncol. 1999 Oct;17(10):3299-306
10506633
Support Care Cancer. 2005 Jun;13(6):381-6
15759136
Br J Cancer. 2009 Mar 10;100(5):713-22
19259092
J Clin Oncol. 2006 Jul 20;24(21):3394-400
16849753
Cancer Epidemiol Biomarkers Prev. 2004 Oct;13(10):1651-9
15466983
Gut. 2003 Oct;52(10):1479-86
12970142
Biochem J. 2007 Oct 1;407(1):113-20
17623010
Eur J Cancer. 1997 Apr;33(4):602-7
9274442
Clin Nutr. 2008 Dec;27(6):793-9
18718696
Cancer. 1998 Feb 1;82(3):553-60
9452274
Cancer. 1974 Jun;33(6):1607-9
4135151
Clin Cancer Res. 2007 Mar 1;13(5):1356-61
17332276
J Clin Oncol. 2004 Jun 15;22(12):2469-76
15197210
J Natl Cancer Inst. 1990 Jul 4;82(13):1127-32
2193166
Ann Oncol. 1997 Mar;8(3):277-83
9137798
Cancer Res. 1991 Nov 15;51(22):6089-93
1657378
J Pain Symptom Manage. 2004 Jan;27(1):85-95
14711473
J Support Oncol. 2008 Jan;6(1):18-25
18257397
J Clin Oncol. 1993 Apr;11(4):762-7
8478668
Clin Nutr. 2007 Aug;26(4):389-99
17499396
Br J Cancer. 2008 Jan 29;98(2):300-8
18182992
Oncol Rep. 2002 Jul-Aug;9(4):887-96
12066227
Cochrane Database Syst Rev. 2007 Jan 24;(1):CD004597
17253515
Cancer Res. 2007 Jul 1;67(13):6512-9
17616713
Cancer. 1990 Sep 15;66(6):1279-82
2205358
Crit Rev Food Sci Nutr. 2003;43(1):89-143
12587987
Gut. 2005 Apr;54(4):540-5
15753541
J Environ Pathol Toxicol Oncol. 2003;22(1):17-28
12678402
J Exp Ther Oncol. 2003 Jul-Aug;3(4):205-19
14567291
J Mol Med (Berl). 2003 Oct;81(10):664-73
12928788
Trends Endocrinol Metab. 2006 Jul;17(5):199-204
16750633
Head Neck. 2008 Jan;30(1):67-74
17615567
Nutrition. 2008 Apr;24(4):305-13
18262758
Eur J Cancer. 2008 May;44(8):1124-32
18375115