Cachexia

1
Cachexia
ICD-10
R 64.
[1]
ICD-9
799.4
[2]
MeSH
D002100
[3]
Cachexia (pronounced /kkksi/, from Greek kakos and hexia: bad condition
[4]
) or wasting syndrome is loss of
weight, muscle atrophy, fatigue, weakness and significant loss of appetite in someone who is not actively trying to
lose weight. The formal definition of cachexia is the loss of body mass that cannot be reversed nutritionally: even if
the affected patient eats more calories, lean body mass will be lost, indicating there is a fundamental pathology in
place. Cachexia is seen in patients with cancer, AIDS,
[5]
chronic obstructive lung disease, congestive heart failure,
tuberculosis, familial amyloid polyneuropathy, and mercury poisoning (acrodynia).
It is a positive risk factor for deathmeaning that if the patient has cachexia, the chance of death from the
underlying condition is increased dramatically. It can be a sign of various underlying disorders; when a patient
presents with cachexia, a doctor will generally consider the possibility of cancer, metabolic acidosis (from decreased
protein synthesis and increased protein catabolism), certain infectious diseases (e.g. tuberculosis, AIDS),chronic
pancreatitis, and some autoimmune disorders, or addiction to drugs such as amphetamines or cocaine. Cachexia
physically weakens patients to a state of immobility stemming from loss of appetite, asthenia, and anemia, and
response to standard treatment is usually poor.
[6]

[7]
Disease settings
Cachexia is often seen in end-stage cancer, and in that context is called "cancer cachexia."
It was also prevalent in HIV patients before the advent of highly active anti-retroviral therapy (HAART) for that
condition; now it is seen less frequently in those countries where such treatment is available. It is this characteristic
that prompted a common African name for AIDS, "slim disease".
In those patients who have congestive heart failure, there is also a cachectic syndrome. Also, a cachexia
co-morbidity is seen in patients that have any of the range of illnesses classified as "COPD" (chronic obstructive
pulmonary disease), particularly emphysema. Some severe cases of schizophrenia can present this condition where it
is named vesanic cachexia (from vesania, a Latin term for insanity).
In each of these settings there is full-body wasting, which hits the skeletal muscle especially hard, resulting in
muscle atrophy and great muscle loss. In most cases Cahchexia can be reversed with just eating. However, when
presenting comorbidly with malabsorbtion syndrome, (as seen, for example, in Crohn's Disease or Celiac Disease)
simply consuming more food is not sufficient to reverse wasting and the malabsorbtion must be treated before the
patient will be able to stabilize body mass.
[8]
Cachexia
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Mechanism
The exact mechanism in which these diseases cause cachexia is poorly understood, but there is probably a role for
inflammatory cytokines such as tumor necrosis factor-alpha (TNF-)which is also nicknamed cachexin (also
spelled cachectin) for this reason, Interferon gamma (IFN), and Interleukin 6 (IL-6), as well as the tumor-secreted
proteolysis inducing factor (PIF).
Related malnutrition syndromes are kwashiorkor and marasmus, although these do not always have an underlying
causative illness; they are most often symptomatic of severe malnutrition.
Those suffering from the eating disorder anorexia nervosa appear to have high plasma levels of ghrelin. Ghrelin
levels are also high in patients who have cancer-induced cachexia.
[9]
Treatment
Currently, there are no widely accepted drugs to treat cachexia and there are no FDA-approved drugs to treat cancer
cachexia.
Cachexia may be treated by steroids such as corticosteroids or drugs that mimic progesterone, which increase
appetite, may reverse weight loss but have no evidence of reversing muscle loss.
[10]
Medical marijuana has been
allowed for the treatment of cachexia in some states such as Michigan, Washington, Oregon, California, and
Colorado.
[10]

[11]
Drugs in development
Three Phase 2 clinical presentations occurred at ASCO 2010 with the following results:
ALD518 is a humanized anti-IL-6 antibody. Method: 124 patients with advanced NSCLC were randomized to 1 of 4
treatment groups (~30/group). Conclusions: ALD518 given to pts with NSCLC was safe and well tolerated. ALD518
improved the lung symptom score, reversed fatigue, and there was less loss of LBM (-0.19kg on ALD518 vs.
-1.50kg on placebo).
[12]
GTx-024 is a Selective Adrenergic Receptor Modulator (SARM). Method: 159 patients with either non-small cell
lung cancer, colorectal cancer, non-Hodgkin's lymphoma, chronic lymphocytic leukemia or breast cancer were
randomized to oral GTx-024 (3mg or 1mg) or placebo daily for 16 weeks. Results: A statistically significant
increase in LBM (lean body mass) was observed in both treatment groups compared to baseline (1mg, P=0.001;
3mg, P=0.045).
[13]
VT-122 is a co-administration of propranolol and etodolac. Method: 37 patients with advanced NSCLC were
randomized to 1 of 3 treatment groups (~12/group). Results: A statistically significant difference was observed in the
proportion of subjects who responded with an improvement of 5% in LBM at Week 12 (Group A, control, n =
0/12; Group B, low dose VT-122, n = 7/12 p = 0.0191; Group C, high dose VT-122, n = 5/12, p = 0.0174). No
patient in Group A gained any lean body mass. An increasing trend in improvement was seen at Weeks 6 and 9 for
Group B and C.
[14]
The world's leading scientists gathered at the 5th annual meeting of the Society on Cachexia and Wasting Disorders
in Barcelona December 58, 2009 to present data on various molecules in development. Kung et al. report highlights
from the 5th Cachexia Conference held in December 2009 in Barcelona, Spain.
[15]
Novel therapeutic approaches
shown here include type 4 melanocortin receptor antagonist SNT 207979, an IL-6 antagonism ALD518, the appetite
promoting synthetic ghrelin SUN11031, the soluble myostatin decoy receptor ActRIIB-Fc, the fast skeletal muscle
troponin activating substance CK-2017357, the anti-catabolic/anabolic transforming agent MT-102, the
anti-inflammatory agent celecoxib, testosterone supplementation and vitamin D.
Two of the presenting companies were Cytokinetics and Ohr Pharmaceutical. Cytokinetics' molecule acts as a
skeletal muscle activator by making certain proteins more sensitive to calcium. Potential treatment for diseases and
Cachexia
3
conditions associated with aging, muscle wasting or neuromuscular dysfunction. Ohr Pharmaceutical's drug,
OHR/AVR118, modulates pro-inflammatory chemokine and cytokine synthesis, including TNF-alpha.
A 2007 systematic review of n-3 fatty acids and cachexia found seventeen studies, eight of which were high-quality.
It concluded that there was evidence that oral n-3 fatty acid supplements benefit cancer patients, improving appetite,
weight and quality of life.
[16]
A 2009 trial found that a supplement of eicosapentaenoic acid helped cancer patients
retain muscle mass.
[17]
In a study published 2010, researchers demonstrated a link between cachexia and activin and myostatin activity, and
successfully reversed the effects in mice, by inhibiting that activity through treatment with a soluble version of the
ActRIIB receptor (sActRIIB).
[18]
See also
Progressive disease
Terminal illness
References
[1] http:/ / apps.who.int/ classifications/ apps/ icd/ icd10online/ ?gr50. htm+ r64
[2] http:/ / www. icd9data. com/ getICD9Code.ashx?icd9=799. 4
[3] http:/ / www. nlm. nih.gov/ cgi/ mesh/ 2009/ MB_cgi?field=uid& term=D002100
[4] http:/ / www. merriam-webster. com/ dictionary/ Cachexia
[5] Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. pp.1169.
ISBN1-4160-2999-0.
[6] Lainscak M, Podbregar M, Anker SD (December 2007). "How does cachexia influence survival in cancer, heart failure and other chronic
diseases?". Curr Opin Support Palliat Care 1 (4): 299305. doi:10.1097/SPC.0b013e3282f31667. PMID18685379.
[7] Bossola M, Pacelli F, Doglietto GB (August 2007). "Novel treatments for cancer cachexia" (http:/ / www. expertopin. com/ doi/ abs/ 10.
1517/ 13543784. 16. 8. 1241). Expert Opin Investig Drugs 16 (8): 124153. doi:10.1517/13543784.16.8.1241. PMID17685872. .
[8] Beck, Ivan T. (August 1964). "Treatment of Malabsorbtion Syndrome". Canadian Medical Association Journal 91 (6): 301-302.
PMID1927227.
[9] Garcia JM, Garcia-Touza M, Hijazi RA, Taffet G, Epner D, Mann D, Smith RG, Cunningham GR, Marcelli M (May 2005). "Active ghrelin
levels and active to total ghrelin ratio in cancer-induced cachexia" (http:/ / jcem. endojournals. org/ cgi/ pmidlookup?view=long&
pmid=15713718). J. Clin. Endocrinol. Metab. 90 (5): 29206. doi:10.1210/jc.2004-1788. PMID15713718. .
[10] Gagnon B, Bruera E (May 1998). "A review of the drug treatment of cachexia associated with cancer". Drugs 55 (5): 67588.
doi:10.2165/00003495-199855050-00005. PMID9585863.
[11] Yavuzsen T, Davis MP, Walsh D, LeGrand S, Lagman R (November 2005). "Systematic review of the treatment of cancer-associated
anorexia and weight loss". J. Clin. Oncol. 23 (33): 850011. doi:10.1200/JCO.2005.01.8010. PMID16293879.
[12] J.R. Rigas et al (June 2010). [http:// http:/ / www.asco. org/ ASCOv2/ Meetings/ Abstracts?& vmview=abst_detail_view& confID=74&
abstractID=50646 "Affect of ALD518, a humanized anti-IL-6 antibody, on lean body mass loss and symptoms in patients with advanced
non-small cell lung cancer (NSCLC): Results of a phase II randomized, double-blind safety and efficacy trial"]. J Clin Oncol 28 (1534). http://
.
[13] M.S. Steiner et al (June 2010). "Effect of GTx-024, a selective androgen receptor modulator (SARM), on stair climb performance and
quality of life (QOL) in patients with cancer cachexia" (http:/ / www. asco. org/ ASCOv2/ Meetings/ Abstracts?& vmview=abst_detail_view&
confID=74& abstractID=52947). J Clin Oncol 28 (1534). .
[14] G. S. Bhattacharyya et al (June 2010). "Phase II study evaluating safety and efficacy of coadministering propranolol and etodolac for
treating cancer cachexia" (http:/ / www. asco.org/ ASCOv2/ Meetings/ Abstracts?& vmview=abst_detail_view& confID=74&
abstractID=49474). J Clin Oncol 28 (1534). .
[15] Kung T et al (April 2010). "Novel treatment approaches to cachexia and sarcopenia: highlights from the 5th Cachexia Conference". Expert
Opin Investig Drugs 19 (4): 579585. doi:10.1517/13543781003724690. PMID20367196.
[16] Colomer R, Moreno-Nogueira JM, Garca-Luna PP, et al. (May 2007). "N-3 fatty acids, cancer and cachexia: a systematic review of the
literature". Br. J. Nutr. 97 (5): 82331. doi:10.1017/S000711450765795X. PMID17408522.
[17] Ryan AM, Reynolds JV, Healy L, et al. (2009). "Enteral nutrition enriched with eicosapentaenoic acid (EPA) preserves lean body mass
following esophageal cancer surgery: results of a double-blinded randomized controlled trial". Ann. Surg. 249 (3): 35563.
doi:10.1097/SLA.0b013e31819a4789. PMID19247018.
[18] Zhou, Xiaolan; Wang, Jin Lin; Lu, John; Song, Yanping; Kwak, Keith S.; Jiao, Qingsheng; Rosenfeld, Robert; Chen, Qing; Boone, Thomas;
Simonet, W. Scott; Lacey, David L.; Goldberg, Alfred L.; Han, H.Q. (2010). "Reversal of Cancer Cachexia and Muscle Wasting by ActRIIB
Antagonism Leads to Prolonged Survival". Cell 142 (4): 53143. doi:10.1016/j.cell.2010.07.011. PMID20723755.
Cachexia
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External links
Manifestations (http:/ / www. ncbi. nlm. nih. gov/ books/ bv. fcgi?& rid=cmed6. section. 40200) and treatment
(http:/ / www. ncbi. nlm. nih. gov/ books/ bv. fcgi?rid=cmed6. section. 40218) of cachexia, from Cancer Medicine
Scientists find key to 'wasting syndrome' seen in cancer, AIDS (U.S. Department of Veterans Affairs) (http:/ /
www. research. va. gov/ news/ press_releases/ wasting-syndrome-1209802. cfm)
Article Sources and Contributors
5
Article Sources and Contributors
Cachexia Source: http://en.wikipedia.org/w/index.php?oldid=393810540 Contributors: Abrech, Allencaron, Andycjp, Angr, Arcadian, ArcadianOnUnsecuredLoc, Biblthmp, Brutaldeluxe,
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