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Journal of Pain and Symptom Management Dec 2021Few pharmacological interventions are available for cancer-associated anorexia and cachexia. Mirtazapine has been suggested for use in cancer-associated anorexia and... (Randomized Controlled Trial)
Randomized Controlled Trial
CONTEXT
Few pharmacological interventions are available for cancer-associated anorexia and cachexia. Mirtazapine has been suggested for use in cancer-associated anorexia and cachexia.
OBJECTIVES
This study was conducted to assess the efficacy and tolerability of mirtazapine in cancer-associated anorexia and cachexia.
METHODS
A double-blind placebo-controlled randomized trial. The study included 120 incurable solid tumour patients with anorexia (appetite loss ≥4 on 0 - 10 scale, 10 = maximum appetite loss), cachexia (>5% body weight loss over 6 months or >2% plus body mass index <20) and depression score ≤3 on 0-6 scale (6 = extreme feelings of depression). Patients were 1:1 randomized to receive mirtazapine 15mg daily at night for 8 weeks or placebo. The primary endpoint was change in appetite from baseline to day 28. Other outcomes included changes in quality-of-life, fatigue, depressive symptoms, body weight, lean body mass, handgrip strength, inflammatory markers, adverse events and survival.
RESULTS
48 (80%) patients in the mirtazapine arm and 52 (87%) in the placebo were assessable for the 1ry endpoint. Appetite score increased significantly with mirtazapine as well as with placebo (P < 0.0001 each). The increase in appetite score did not differ significantly between the two arms in the per-protocol and intention-to-treat analysis (P = 0.472 and 0.462, respectively). Mirtazapine was associated with significantly less increase in depressive symptoms and higher prevalence of somnolence. The change in other outcomes did not differ significantly between mirtazapine and placebo.
CONCLUSION
Mirtazapine 15mg at night for 28 days is no better than placebo in improving the appetite of incurable solid tumor patients with cancer-associated anorexia and cachexia.
Topics: Anorexia; Cachexia; Double-Blind Method; Hand Strength; Humans; Mirtazapine; Neoplasms
PubMed: 34051293
DOI: 10.1016/j.jpainsymman.2021.05.017 -
Journal of Feline Medicine and Surgery Mar 2018Practical relevance: Hepatic lipidosis (HL) is the most common form of liver dysfunction in cats. If recognized early and treated appropriately, the prognosis is good;... (Review)
Review
UNLABELLED
Practical relevance: Hepatic lipidosis (HL) is the most common form of liver dysfunction in cats. If recognized early and treated appropriately, the prognosis is good; if not, the prognosis is grave. Clinical challenges: Distinguishing HL as idiopathic or secondary is critical since the presence of a concurrent disease affects the therapeutic plan and the prognosis.
AUDIENCE
Despite the unique and severe nature of a cat's response to anorexia and the complexity of the metabolic changes underlying this condition, the clinical acumen and technical ability to effectively diagnose and treat HL are readily available to all small animal practitioners. Patient group: Although many species develop a 'fatty liver', the cat is one of relatively few species that suffer from HL. The classic presentation is that of an overweight cat that stops eating for days to weeks, losing weight in the process. Equipment: Abdominal ultrasound is frequently employed in the diagnostic work-up of an anorectic cat; ultrasonographic findings often support a presumptive diagnosis, provide samples for cytology and, perhaps most importantly, help identify concurrent conditions that must be addressed for therapeutic success. All of the equipment necessary for essential nutritional intervention in an anorectic cat is readily available and easily affordable. Evidence base: The material for this review draws heavily on a relatively large number of original studies, excellent reviews by recognized experts, and informative communication with experienced clinicians, hence the term 'collective effort'.
Topics: Animals; Anorexia; Cat Diseases; Cats; Fatty Liver
PubMed: 29478399
DOI: 10.1177/1098612X18758591 -
Nutrients Apr 2019Omega-3 polyunsaturated fatty acids (PUFAs) are considered immunonutrients and are commonly used in the nutritional therapy of cancer patients due to their ample... (Review)
Review
Omega-3 polyunsaturated fatty acids (PUFAs) are considered immunonutrients and are commonly used in the nutritional therapy of cancer patients due to their ample biological effects. Omega-3 PUFAs play essential roles in cell signaling and in the cell structure and fluidity of membranes. They participate in the resolution of inflammation and have anti-inflammatory and antinociceptive effects. Additionally, they can act as agonists of G protein-coupled receptors, namely, GPR40/FFA1 and GPR120/FFA4. Cancer patients undergo complications, such as anorexia-cachexia syndrome, pain, depression, and paraneoplastic syndromes. Interestingly, the 2017 European Society for Clinical Nutrition and Metabolism (ESPEN) guidelines for cancer patients only discuss the use of omega-3 PUFAs for cancer-cachexia treatment, leaving aside other cancer-related complications that could potentially be managed by omega-3 PUFA supplementation. This critical review aimed to discuss the effects and the possible underlying mechanisms of omega-3 PUFA supplementation in cancer-related complications. Data compilation in this critical review indicates that further investigation is still required to assess the factual benefits of omega-3 PUFA supplementation in cancer-associated illnesses. Nevertheless, preclinical evidence reveals that omega-3 PUFAs and their metabolites might modulate pivotal pathways underlying complications secondary to cancer, indicating that this is a promising field of knowledge to be explored.
Topics: Anorexia; Depressive Disorder, Major; Fatty Acids, Omega-3; Humans; Neoplasms; Pain; Paraneoplastic Syndromes
PubMed: 31035457
DOI: 10.3390/nu11050945 -
Journal of Cachexia, Sarcopenia and... Apr 2023Anorexia/appetite loss in older subjects is frequently underrecognized in clinical practice, which may reflect deficient understanding of clinical sequelae. Therefore,... (Review)
Review
Anorexia/appetite loss in older subjects is frequently underrecognized in clinical practice, which may reflect deficient understanding of clinical sequelae. Therefore, we performed a systematic literature review to assess the morbidity and mortality burden of anorexia/appetite loss in older populations. Following PRISMA guidelines, searches were run (1 January 2011 to 31 July 2021) in PubMed, Embase® and Cochrane databases to identify English language studies of adults aged ≥ 65 years with anorexia/appetite loss. Two independent reviewers screened titles, abstracts and full text of identified records against pre-defined inclusion/exclusion criteria. Population demographics were extracted alongside risk of malnutrition, mortality and other outcomes of interest. Of 146 studies that underwent full-text review, 58 met eligibility criteria. Most studies were from Europe (n = 34; 58.6%) or Asia (n = 16; 27.6%), with few (n = 3; 5.2%) from the United States. Most were conducted in a community setting (n = 35; 60.3%), 12 (20.7%) were inpatient based (hospital/rehabilitation ward), 5 (8.6%) were in institutional care (nursing/care homes) and 7 (12.1%) were in other (mixed or outpatient) settings. One study reported results separately for community and institutional settings and is counted in both settings. Simplified Nutritional Appetite Questionnaire (SNAQ Simplified, n = 14) and subject-reported appetite questions (n = 11) were the most common methods used to assess anorexia/appetite loss, but substantial variability in assessment tools was observed across studies. The most commonly reported outcomes were malnutrition and mortality. Malnutrition was assessed in 15 studies, with all reporting a significantly higher risk of malnutrition in older individuals with anorexia/appetite loss (vs. without) regardless of country or healthcare setting (community n = 9, inpatient n = 2, institutional n = 3, other n = 2). Of 18 longitudinal studies that assessed mortality risk, 17 (94%) reported a significant association between anorexia/appetite loss and mortality regardless of either healthcare setting (community n = 9, inpatient n = 6, institutional n = 2) or method used to assess anorexia/appetite loss. This association between anorexia/appetite loss and mortality was observed in cohorts with cancer (as expected) but was also observed in older populations with a range of comorbid conditions other than cancer. Overall, our findings demonstrate that, among individuals aged ≥ 65 years, anorexia/appetite loss is associated with increased risk of malnutrition, mortality and other negative outcomes across community, care home and hospital settings. Such associations warrant efforts to improve and standardize screening, detection, assessment and management of anorexia/appetite loss in older adults.
Topics: Humans; Aged; Anorexia; Appetite; Malnutrition; Hospitals; Europe
PubMed: 36807868
DOI: 10.1002/jcsm.13186 -
Drugs of Today (Barcelona, Spain : 1998) Sep 2016Cachexia is a multiorgan, multifactorial and often irreversible wasting syndrome associated with cancer and other serious, chronic illnesses including AIDS, chronic...
Cachexia is a multiorgan, multifactorial and often irreversible wasting syndrome associated with cancer and other serious, chronic illnesses including AIDS, chronic heart failure, chronic kidney disease and chronic obstructive pulmonary disease. Treatment of the patient with cachexia is currently targeted to correcting the two underlying features of the condition: anorexia and metabolic disturbances. Greater understanding of the mechanisms behind cachexia and muscle wasting have led to new therapeutic possibilities, however. Several classes of drugs are under active development for cachexia including drugs acting on hormone receptors or cytokine receptors, myostatin/activin pathway antagonists, beta-adrenoceptor agonists and cannabinoids. This review will cover the pathophysiology, epidemiology, diagnosis, treatment, drug candidates under active development and targets for therapeutic intervention of cachexia.
Topics: Anorexia; Cachexia; Cannabinoids; Combined Modality Therapy; Diagnosis, Differential; Dietary Supplements; Glucocorticoids; Hormones; Humans; Resistance Training; Signal Transduction; Testosterone Congeners
PubMed: 27883118
DOI: 10.1358/dot.2016.52.9.2545017 -
Primary Care Sep 2019The burden of nonpain symptoms such as anorexia, constipation, nausea, and vomiting contribute to patient suffering throughout the course of advanced illness. It is... (Review)
Review
The burden of nonpain symptoms such as anorexia, constipation, nausea, and vomiting contribute to patient suffering throughout the course of advanced illness. It is important to address symptom control throughout the disease trajectory, and especially at the end of life. Primary care clinicians must recognize these symptoms early, provide ongoing assessment, and keep abreast of evidence-based management strategies, including valid clinical protocols.
Topics: Anorexia; Constipation; Critical Illness; Humans; Nausea; Palliative Care; Prevalence; Primary Health Care; Vomiting
PubMed: 31375185
DOI: 10.1016/j.pop.2019.05.002 -
Journal of Advanced Research Apr 2024Cancer-associated cachexia is a multi-organ disorder associated with progressive weight loss due to a variable combination of anorexia, systemic inflammation and... (Review)
Review
BACKGROUND
Cancer-associated cachexia is a multi-organ disorder associated with progressive weight loss due to a variable combination of anorexia, systemic inflammation and excessive energy wasting. Considering the importance of immunoregulation in cachexia, it still lacks a complete understanding of the immunological mechanisms in cachectic progression.
AIM OF REVIEW
Our aim here is to describe the complex immunoregulatory system in cachexia. We summarize the effects and translational potential of the immune system on the development of cancer-associated cachexia and we attempt to conclude with thoughts on precise and integrated therapeutic strategies under the complex immunological context of cachexia.
KEY SCIENTIFIC CONCEPTS OF REVIEW
This review is focused on three main key concepts. First, we highlight the inflammatory factors and additional mediators that have been identified to modulate this syndrome. Second, we decipher the potential role of immune checkpoints in tissue wasting. Third, we discuss the multilayered insights in cachexia through the immunometabolic axis, immune-gut axis and immune-nerve axis.
Topics: Humans; Cachexia; Neoplasms; Weight Loss; Anorexia; Inflammation
PubMed: 37150253
DOI: 10.1016/j.jare.2023.04.018 -
The Lancet. Oncology Apr 2016Patients with advanced cancer frequently experience anorexia and cachexia, which are associated with reduced food intake, altered body composition, and decreased... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Patients with advanced cancer frequently experience anorexia and cachexia, which are associated with reduced food intake, altered body composition, and decreased functionality. We assessed anamorelin, a novel ghrelin-receptor agonist, on cachexia in patients with advanced non-small-cell lung cancer and cachexia.
METHODS
ROMANA 1 and ROMANA 2 were randomised, double-blind, placebo-controlled phase 3 trials done at 93 sites in 19 countries. Patients with inoperable stage III or IV non-small-cell lung cancer and cachexia (defined as ≥5% weight loss within 6 months or body-mass index <20 kg/m(2)) were randomly assigned 2:1 to anamorelin 100 mg orally once daily or placebo, with a computer-generated randomisation algorithm stratified by geographical region, cancer treatment status, and weight loss over the previous 6 months. Co-primary efficacy endpoints were the median change in lean body mass and handgrip strength over 12 weeks and were measured in all study participants (intention-to-treat population). Both trials are now completed and are registered with ClinicalTrials.gov, numbers NCT01387269 and NCT01387282.
FINDINGS
From July 8, 2011, to Jan 28, 2014, 484 patients were enrolled in ROMANA 1 (323 to anamorelin, 161 to placebo), and from July 14, 2011, to Oct 31, 2013, 495 patients were enrolled in ROMANA 2 (330 to anamorelin, 165 to placebo). Over 12 weeks, lean body mass increased in patients assigned to anamorelin compared with those assigned to placebo in ROMANA 1 (median increase 0·99 kg [95% CI 0·61 to 1·36] vs -0·47 kg [-1·00 to 0·21], p<0·0001) and ROMANA 2 (0·65 kg [0·38 to 0·91] vs -0·98 kg [-1·49 to -0·41], p<0·0001). We noted no difference in handgrip strength in ROMANA 1 (-1·10 kg [-1·69 to -0·40] vs -1·58 kg [-2·99 to -1·14], p=0·15) or ROMANA 2 (-1·49 kg [-2·06 to -0·58] vs -0·95 kg [-1·56 to 0·04], p=0·65). There were no differences in grade 3-4 treatment-related adverse events between study groups; the most common grade 3-4 adverse event was hyperglycaemia, occurring in one (<1%) of 320 patients given anamorelin in ROMANA 1 and in four (1%) of 330 patients given anamorelin in ROMANA 2.
INTERPRETATION
Anamorelin significantly increased lean body mass, but not handgrip, strength in patients with advanced non-small-cell lung cancer. Considering the unmet medical need for safe and effective treatments for cachexia, anamorelin might be a treatment option for patients with cancer anorexia and cachexia.
FUNDING
Helsinn Therapeutics.
Topics: Aged; Anorexia; Cachexia; Carcinoma, Non-Small-Cell Lung; Double-Blind Method; Female; Hand Strength; Humans; Hydrazines; Male; Middle Aged; Neoplasm Staging; Oligopeptides; Treatment Outcome
PubMed: 26906526
DOI: 10.1016/S1470-2045(15)00558-6 -
Current Opinion in Supportive and... Dec 2017In spite of its relevance, treatments for the cancer anorexia and cachexia syndrome (CACS) are not available. One of the agents that recently reached phase III clinical... (Review)
Review
PURPOSE OF REVIEW
In spite of its relevance, treatments for the cancer anorexia and cachexia syndrome (CACS) are not available. One of the agents that recently reached phase III clinical trials is anamorelin. Its development, along with that of other agents for this indication, will be reviewed here, with a focus on the gaps in the current knowledge and future directions.
RECENT FINDINGS
In spite of several targets showing promising results in early development, their difficulties obtaining regulatory approval underscore the need to reconsider the current strategies in drug development and the challenges in the field of CACS.
SUMMARY
Further research is needed in order to meet the challenges of developing treatments for CACS. Preclinical studies should expand our understanding about key regulators of appetite, muscle, and energy metabolism in this setting using models that can be translated reliably to humans. Clinical research efforts should focus on validating the entry criteria, endpoints, outcomes, and the potential synergistic effects and interaction between different targets, nutrition, and exercise interventions. Clinical meaningfulness and significance should be taken into account in the design of clinical trials. It is essential that all key stakeholders are included in the design of future strategies.
Topics: Anorexia; Biomarkers; Cachexia; Drug Approval; Humans; Hydrazines; Neoplasms; Oligopeptides; Quality of Life; Randomized Controlled Trials as Topic; Receptors, Ghrelin; Research Design
PubMed: 28957883
DOI: 10.1097/SPC.0000000000000299 -
Seminars in Musculoskeletal Radiology Aug 2023Anorexia nervosa is a feeding disorder involving intentional weight loss. Restricted dietary intake leads to disturbed bone metabolism due to various factors, notably...
Anorexia nervosa is a feeding disorder involving intentional weight loss. Restricted dietary intake leads to disturbed bone metabolism due to various factors, notably endocrine, that affect bone microarchitecture and incur risk of fracture. Mild to moderate anorexia shows a paradoxical increase in bone marrow adipose tissue, whereas severe forms show gelatinous transformation known as serous atrophy of bone marrow (SABM). Imaging assessment of the mineralized and adipose components uses several techniques: dual-energy X-ray absorptiometry, computed tomography, chemical shift magnetic resonance imaging (MRI), and single-voxel MR spectroscopy. SABM induces MRI bone signal disturbances that can be hard to interpret and may hinder visualization of the fracture line.
Topics: Humans; Anorexia; Bone Marrow; Anorexia Nervosa; Magnetic Resonance Imaging; Adipose Tissue; Fractures, Bone; Atrophy; Bone Density
PubMed: 37748469
DOI: 10.1055/s-0043-1768452