Systematic Review of the Treatment of Cancer-Associated Anorexia and Weight Loss

Yavuzşen, Tuğba; Davis, Mellar P.; Walsh, Declan; LeGrand, Susan B.; Lagman, Ruth

doi:10.1200/jco.2005.01.8010

Cited by 193 publications

(136 citation statements)

References 56 publications

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“…They include mainly appetite stimulants and anabolic agents such as prednisolone [15,51] and progesterone [12,42,43,77] and ghrelin, a ligand which stimulates growth hormone release [44,59]. Anecdotally, the use of α-3 omega fatty acids (eicosapentaenoic acid) [52] and thalidomide (potent anti-TNF activity) have been reported [48].…”

Section: Discussionmentioning

confidence: 99%

Selective Inhibition of NF-kappa-B with NBD Peptide Reduces Tumor- Induced Wasting in a Murine Model of Cancer Cachexia In vivo

Wysong¹,

Asher

Yin

et al. 2011

JCST

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Cancer cachexia is a severe wasting syndrome characterized by the progressive loss of lean body mass and systemic inflammation, which is seen in as many as 80% of patients with advanced malignancy. It accounts for an estimated 20-30% of all cancer-related deaths. The mechanism by which cancer induces skeletal muscle atrophy in cachexia involves tumor-derived cytokines, including TNFα, IL-1, and IL-6. Upon interaction with their unique receptors on skeletal muscle, these cytokines activate NF-kappaB, a transcription factor crucial for atrophy related sarcomere proteolysis to occur. The significance of NF-κB is highlighted in studies demonstrating that genetic inhibition of NF-κB ameliorates cancer-induced muscle loss in vivo. In the present study, we evaluate a selective NF-kappaB inhibitor (NBD peptide) which targets the IkappaB complex to prevent cancer-induced skeletal muscle atrophy in an established mouse model (C26 adenocarcinoma). We identified for the first time that NBD peptide can directly inhibit tumor-induced NFkappaB activation in skeletal muscle, resulting in a decrease loss of lean muscle. We also identified that NBD peptide reduces the expression of the tumor induced ubiquitin ligases MuRF-1 and MAFbx/Atrogin-1 necessary for atrophy. These findings highlight that NBD peptide may be a potential selective therapeutic agent for the treatment of cancer cachexia.

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Section: Discussionmentioning

confidence: 99%

Selective Inhibition of NF-kappa-B with NBD Peptide Reduces Tumor- Induced Wasting in a Murine Model of Cancer Cachexia In vivo

Wysong¹,

Asher

Yin

et al. 2011

JCST

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“…Central mechanisms accounting for dwindling appetite include fatigue, inflammatory signals mediated by cytokines, and hormonal, autonomic, and neuromediator imbalances. [28][29][30] Other comorbidities, including depressive symptoms, psychological distress, social withdrawal, and nausea, can further contribute to this problem. Hunger displays a strong circadian rhythm.…”

Section: Anorexia In Cancer Patientsmentioning

confidence: 99%

Circadian Disruption, Fatigue, and Anorexia Clustering in Advanced Cancer Patients: Implications for Innovative Therapeutic Approaches

et al. 2009

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A disruption of the circadian timing system, as identified by monitoring of marker biorhythms, is common in cancer patients. The recording of the rest-activity rhythm with a wrist actigraph has been commonly used. This noninvasive monitoring allows a robust estimation of circadian disruption. The authors have previously found that altered patterns of circadian rest-activity rhythms are significantly and independently associated with the severity of fatigue and anorexia in patients with metastatic colorectal cancer. Elevated proinflammatory cytokines could partly account for this circadian disruption and its associated constitutional symptoms. Here, the authors present and discuss the data supporting the hypothesis that circadian disruption is often associated with fatigue and anorexia, which in turn further alter and dampen circadian synchronization, thus, creating a vicious cycle. This body of evidence paves the path for innovative therapeutic approaches targeting the circadian timing system in an effort to diminish constitutional symptoms induced by cancer and some anticancer treatments.

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“…There are few pharmacological treatment options for CACS, but it has been shown that this patient population with advanced cancer has the capacity to respond to appetite stimulation therapy (Yavuzsen et al, 2005).…”

mentioning

confidence: 99%

Safety, tolerability and pharmacokinetics of intravenous ghrelin for cancer-related anorexia/cachexia: a randomised, placebo-controlled, double-blind, double-crossover study

Strasser¹,

et al. 2008

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Twenty-one adult patients were randomised to receive ghrelin on days 1 and 8 and placebo on days 4 and 11 or vice versa, given intravenously over a 60-min period before lunch: 10 received 2 mg kg À1 (lower-dose) ghrelin; 11 received 8 mg kg À1 (upper-dose) ghrelin. Active and total ghrelin, growth hormone (GH), and insulin-like growth factor 1 levels were monitored at baseline (4 -5 days before day 1), during treatment days, and at end of study (day 17/18). Drug-related adverse events (assessed by NCI-CTC-toxicity criteria and cardiac examination) did not differ between ghrelin and placebo. No grade 3/4 toxicity or stimulation of tumour growth was observed. The peak increase of GH, a biological marker of ghrelin action, was 25 ng ml À1 with lower-dose and 42 ng ml À1 with upper-dose ghrelin. Morning fasting total ghrelin levels were higher (Po0.05) for upper-dose patients at end of study (3580 pg ml À1 ) than at baseline (990 pg ml À1 ). Insulin-like growth factor 1 levels did not change. At day 8, 81% of patients preferred ghrelin to placebo as against 63% at the end of study. Nutritional intake and eating-related symptoms, measured to explore preliminary efficacy, did not differ between ghrelin and placebo. Ghrelin is well tolerated and safe in patients with advanced cancer. For safety, tolerance, and patients' preference for treatment, no difference was observed between the lower-and upper-dose group.

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Systematic Review of the Treatment of Cancer-Associated Anorexia and Weight Loss

Cited by 193 publications

References 56 publications

Selective Inhibition of NF-kappa-B with NBD Peptide Reduces Tumor- Induced Wasting in a Murine Model of Cancer Cachexia In vivo

Selective Inhibition of NF-kappa-B with NBD Peptide Reduces Tumor- Induced Wasting in a Murine Model of Cancer Cachexia In vivo

Circadian Disruption, Fatigue, and Anorexia Clustering in Advanced Cancer Patients: Implications for Innovative Therapeutic Approaches

Safety, tolerability and pharmacokinetics of intravenous ghrelin for cancer-related anorexia/cachexia: a randomised, placebo-controlled, double-blind, double-crossover study

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