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Nutrition in Clinical Practice :... Apr 2006Cachexia involves progressive loss of adipose tissue and skeletal muscle mass and is common in a number of end-stage diseases. Cachexia causes weakness and immobility,... (Review)
Review
Cachexia involves progressive loss of adipose tissue and skeletal muscle mass and is common in a number of end-stage diseases. Cachexia causes weakness and immobility, reduces the quality of life of the patient, and eventually results in death. We reviewed the medical literature concentrating upon agents that have undergone clinical evaluation for the treatment of patients with cachexia. These agents are discussed, together with their mechanisms of action. Megestrol acetate, corticosteroids, eicosapentaenoic acid, and thalidomide have shown some success in the treatment of cachexia. beta-hydroxy-beta-methylbutyrate, cyclooxygenase inhibitors, adenosine 5'-triphosphate, and growth hormone are undergoing clinical evaluation. Appetite stimulants such as cannabinoids and antiserotonic agents have been shown to be ineffective in preventing progressive weight loss in cachexia. Much of the success in the treatment of cachexia has come from agents capable of blocking protein degradation through the ubiquitin-proteasome proteolytic pathway. Muscle mass can be increased when such agents are combined with agents that stimulate protein synthesis. In order to develop new agents, more fundamental research is required on the cellular mechanisms governing protein synthesis and degradation in skeletal muscle in cachexia.
Topics: Adipose Tissue; Adrenal Cortex Hormones; Cachexia; Eicosapentaenoic Acid; Energy Metabolism; Humans; Muscle, Skeletal; Progestins; Protein Biosynthesis; Thalidomide
PubMed: 16556927
DOI: 10.1177/0115426506021002168 -
Nutrition and Cancer 1987Hydrazine sulfate is an anticachexia agent which interrupts host energy wasting as a result of the malignant process. An inhibitor of gluconeogenesis at the... (Clinical Trial)
Clinical Trial Review
Hydrazine sulfate is an anticachexia agent which interrupts host energy wasting as a result of the malignant process. An inhibitor of gluconeogenesis at the phosphoenolpyruvate carboxykinase (PEP CK) reaction, this agent has been shown in randomized, placebo-controlled, double-blind trials to improve glucose tolerance, reduce glucose turnover, increase caloric intake, and increase or stabilize weight; in single-arm controlled trials, this agent has been shown to increase appetite, improve performance status, decrease pain, diminish anorexia, normalize laboratory indices, stabilize tumor growth, induce tumor regression, and promote survival, while inducing little to no important clinical side effects. In view of its demonstrated capacity to effect anticancer response, this drug is suggested for trial as a sole agent in early drug-resistant cancer, in combination with cytotoxic and related therapies, and in conjunction with total parenteral nutrition. It is postulated that effective control of the mechanisms associated associated with cancer cachexia may contribute to control of malignant disease.
Topics: Cachexia; Clinical Trials as Topic; Double-Blind Method; Gluconeogenesis; Humans; Hydrazines; Neoplasms; Parenteral Nutrition, Total
PubMed: 3104888
DOI: 10.1080/01635588709513912 -
American Society of Clinical Oncology... 2015Many important advances have occurred in the field of cancer cachexia over the past decade, including progress in understanding the mechanisms of the cancer... (Review)
Review
Many important advances have occurred in the field of cancer cachexia over the past decade, including progress in understanding the mechanisms of the cancer anorexia-cachexia syndrome (CACS) and the development of promising pharmacologic and supportive care interventions. However, no approved agents for cancer cachexia currently exist, emphasizing the unmet need for an effective pharmacologic therapy. This article reviews the key elements of CACS assessment in daily practice, the contribution of nutritional impact symptoms (NIS), the evidence for current pharmacologic options, and promising anticachexia agents in perclinical and clinical trials. It also proposes a model for multimodality therapy and highlights issues pertinent to CACS in patients with pancreatic, gastric, and esophageal cancer.
Topics: Anorexia; Cachexia; Humans; Neoplasms; Quality of Life; Randomized Controlled Trials as Topic
PubMed: 25993178
DOI: 10.14694/EdBook_AM.2015.35.e229 -
Oncology (Williston Park, N.Y.) Jan 2017Weight loss is distressing to cancer patients and caregivers. Anorexia/cachexia syndrome is characterized by lipolysis and the loss of lean body mass, and is not... (Review)
Review
Weight loss is distressing to cancer patients and caregivers. Anorexia/cachexia syndrome is characterized by lipolysis and the loss of lean body mass, and is not reversible by increasing caloric intake. The pathophysiology of cancer cachexia is complex and includes symptoms that impact caloric intake, as well as chronic inflammation, hypermetabolism, and hormonal alterations. Cancer patients require routine screening for cachexia and, ideally, interventions should be initiated in the early stages of weight loss. No guidelines exist for the treatment of cancer cachexia. Appetite stimulants, such as megestrol acetate and glucocorticoids, have been shown to increase appetite and weight; however, single pharmaceutical interventions alone for cachexia do not result in meaningful functional outcomes. In the future, clinicians should consider multimodality treatment that is personalized for each patient. These interventions would include nutritional counseling, assessing and treating symptoms that have an impact on caloric intake, and a rational combination of pharmacologic approaches directed at underlying pathophysiology. Use of an appetite stimulant could be considered for patients who exhibit decreased appetite. Treatment with an anti-inflammatory agent should be considered for patients with elevated C-reactive protein, and hormonal alterations resulting from anti-cachexia therapy should be thoughtfully addressed.
Topics: Appetite Stimulants; Cachexia; Energy Intake; Humans; Neoplasms; Nutritional Support; Practice Guidelines as Topic
PubMed: 28090619
DOI: No ID Found -
Antioxidants & Redox Signaling Feb 2023Cancer is frequently associated with the early appearance of cachexia, a multifactorial wasting syndrome. If not present at diagnosis, cachexia develops either as a... (Review)
Review
Cancer is frequently associated with the early appearance of cachexia, a multifactorial wasting syndrome. If not present at diagnosis, cachexia develops either as a result of tumor progression or as a side effect of anticancer treatments, especially of standard chemotherapy, eventually representing the direct cause of death in up to one-third of all cancer patients. Cachexia, within its multiorgan affection, is characterized by severe loss of muscle mass and function, representing the most relevant subject of preclinical and clinical investigation. The pathogenesis of muscle wasting in cancer- and chemotherapy-induced cachexia is complex, and encompasses heightened protein catabolism and reduced anabolism, disrupted mitochondria and energy metabolism, and even neuromuscular junction dismantling. The mechanisms underlying these alterations are still controversial, especially concerning the molecular drivers that could be targeted for anticachexia therapies. Inflammation and mitochondrial oxidative stress are among the principal candidates; the latter being extensively discussed in the present review. Several approaches have been tested to modulate the redox homeostasis in tumor hosts, and to counteract cancer- and chemotherapy-induced muscle wasting, from exercise training to distinct classes of direct or indirect antioxidants. We herein report the most relevant results obtained from both preclinical and clinical trials. Including the assessment and the treatment of altered redox balance in the clinical management of cancer patients is still a big challenge. The available evidence suggests that fortifying the antioxidant defenses by either pharmacological or nonpharmacological strategies will likely improve cachexia and eventually the outcome of a broad cancer patient population. 38, 352-370.
Topics: Humans; Cachexia; Muscle, Skeletal; Neoplasms; Muscular Atrophy; Mitochondria; Oxidative Stress; Antineoplastic Agents
PubMed: 36310444
DOI: 10.1089/ars.2022.0149 -
Clinical Cancer Research : An Official... Aug 2016Cancer cachexia is a multifactorial syndrome characterized by an ongoing loss of skeletal muscle mass, which negatively affects quality of life and portends a poor... (Review)
Review
Cancer cachexia is a multifactorial syndrome characterized by an ongoing loss of skeletal muscle mass, which negatively affects quality of life and portends a poor prognosis. Numerous molecular substrates and mechanisms underlie the dysregulation of skeletal muscle synthesis and degradation observed in cancer cachexia, including proinflammatory cytokines (TNFα, IL1, and IL6), and the NF-κB, IGF1/AKT/mTOR, and myostatin/activin-SMAD pathways. Recent preclinical and clinical studies have demonstrated that anti-cachexia drugs (such as MABp1 and soluble receptor antagonist of myostatin/activin) not only prevent muscle wasting but also may prolong overall survival. In this review, we focus on the significance of cachexia signaling in patients with cancer and highlight promising drugs targeting tumor cachexia in clinical development. Clin Cancer Res; 22(16); 3999-4004. ©2016 AACR.
Topics: Animals; Antineoplastic Agents; Biomarkers; Cachexia; Clinical Trials as Topic; Cytokines; Humans; Molecular Targeted Therapy; Muscle Development; Muscle, Skeletal; Muscular Atrophy; Neoplasms; Proteolysis; Signal Transduction; Translational Research, Biomedical
PubMed: 27340276
DOI: 10.1158/1078-0432.CCR-16-0495 -
Expert Opinion on Pharmacotherapy Jun 2023Cachexia is a complex multi-factorial syndrome characterized by anorexia, inflammation, body, and skeletal muscle wasting. Early diagnosis and intervention via a... (Review)
Review
INTRODUCTION
Cachexia is a complex multi-factorial syndrome characterized by anorexia, inflammation, body, and skeletal muscle wasting. Early diagnosis and intervention via a multimodal approach combining nutritional counseling, exercise, and pharmacological agents is advisable. However, no effective treatment options are currently available in the clinical setting.
AREAS COVERED
The present work is a review of emerging treatment options for cancer cachexia, including mainly, but not only, pharmacological approaches. The main interest is on drugs currently investigated in clinical trials; however, promising pre-clinical options are presented as well. Data were collected using PubMed and ClinicalTrials.gov databases, including studies of the last 20 years and active clinical trials.
EXPERT OPINION
The lack of effective therapeutic approaches against cachexia results from several issues, among which a reduced number of studies focused on new drugs. Furthermore, the translation of pre-clinical results in the clinical practice is a hard mission, and it must be considered whether drugs target cachexia as a consequence of acting directly on the tumor. Indeed, dissecting antineoplastics from direct anti-cachexia effects is needed to elucidate the mechanisms of action of specific drugs. This is necessary for their inclusion into multimodal approaches, which nowadays are considered the best way to tackle cachexia.
Topics: Humans; Neoplasms; Cachexia; Exercise; Counseling
PubMed: 37132359
DOI: 10.1080/14656566.2023.2209316 -
Molecules (Basel, Switzerland) Jul 2022Medicinal and food homologous adlay ( L. var. Stapf) plays an important role in natural products promoting human health. We demonstrated the systematic actional... (Review)
Review
Medicinal and food homologous adlay ( L. var. Stapf) plays an important role in natural products promoting human health. We demonstrated the systematic actional mechanism of functional ingredients in adlay to promote human health, based on the PubMed, CNKI, Google, and ISI Web of Science databases from 1988 to 2022. Adlay and its extracts are rich in 30 ingredients with more than 20 health effects based on human and animal or cell cultures: they are anti-cancer, anti-inflammation, anti-obesity, liver protective, anti-virus, gastroprotective, cardiovascular protective, anti-hypertension, heart disease preventive, melanogenesis inhibiting, anti-allergy, endocrine regulating, anti-diabetes, anti-cachexia, osteoporosis preventive, analgesic, neuroprotecting, suitable for the treatment of gout arthritis, life extending, anti-fungi, and detoxifying effects. Function components with anti-oxidants are rich in adlay. These results support the notion that adlay seeds may be one of the best functional foods and further reveal the action mechanism of six major functional ingredients (oils, polysaccharides, phenols, phytosterols, coixol, and resistant starch) for combating diseases. This review paper not only reveals the action mechanisms of adding adlay to the diet to overcome 17 human diseases, but also provides a scientific basis for the development of functional foods and drugs for the treatment of human diseases.
Topics: Animals; Anti-Allergic Agents; Coix; Functional Food; Humans; Phenols; Plant Extracts
PubMed: 35956759
DOI: 10.3390/molecules27154808 -
Current Opinion in Supportive and... Sep 2023To explore the current evidence relating to the practical management of cancer cachexia in palliative care. (Review)
Review
PURPOSE OF REVIEW
To explore the current evidence relating to the practical management of cancer cachexia in palliative care.
RECENT FINDINGS
The authors found a growing evidence base including the publication of several expert guidelines since 2020. Guidelines identified the need for individualised nutritional and physical exercise support as the mainstay of cachexia management. Dietician and allied health professional referrals are recommended for the best patient outcomes. Limitations of nutritional support and exercise are acknowledged. Patient outcomes from multimodal anti-cachexia therapy are awaited at this time. Communication about the mechanisms of cachexia and nutritional counselling are identified as ways to reduce distress. Evidence supporting the use of pharmacological agents remains insufficient to make recommendations. Corticosteroids and progestins may be offered for symptom relief in refractory cachexia, taking into consideration well-documented side effects. Emphasis is placed on adequately managing nutritional impact symptoms. A specific role for palliative care clinicians and the use of existing palliative care guidelines in managing cancer cachexia were not identified.
SUMMARY
Current evidence recognises the inherently palliative nature of cancer cachexia management, and practical guidance correlates with the tenets of palliative care. Individualised approaches to support nutritional intake, physical exercise and alleviate symptoms that accelerate cachexia processes are currently recommended.
Topics: Humans; Palliative Care; Quality of Life; Cachexia; Nutritional Support; Neoplasms
PubMed: 37384429
DOI: 10.1097/SPC.0000000000000655 -
Mini Reviews in Medicinal Chemistry Dec 2002The full-scale commercial appearance of antibiotics in the 1950's caused a shift of the nature of our lethal diseases from infectious/acute to non-infectious/chronic. In... (Review)
Review
The full-scale commercial appearance of antibiotics in the 1950's caused a shift of the nature of our lethal diseases from infectious/acute to non-infectious/chronic. In this situation, biological response modifiers (BRM's), which are not based on selective toxicity, are expected to be useful. There exist several types of BRM's, including retinoids which act directly on cells at the gene expression level, and thalidomide (and related molecules) which modulate internal circumstances of our body. We have been engaged in medicinal chemical/structural development studies based on these bio-active compounds. Retinoids include all-trans-retinoic acid (ATRA), a major active form of vitamin A (retinol), and its bio-isosters, which elicit their biological effects by binding to their nuclear receptors, RAR's. ATRA has been used in differentiation therapy [typically for the treatment of acute promyelocytic leukemia (APL)] and the treatment of dermatological diseases. Our structural development studies of retinoids, including computer-assisted molecular design has yielded class/subtype-selective agonists, synergists and antagonists of RAR's and their partner nuclear receptors, RXR's. Thalidomide elicits a wide range of pharmacological effects, including anti-cachexia, anti-angiogenic and anti-metastatic activities. We have found that thalidomide is a multi-target drug. Hypothetical target events/molecules of thalidomide include TNF-alpha production, nuclear androgen receptor, aminopeptidases, and alpha-glucosidase. Specific and potent compounds for each of these target phenomena/molecules have been prepared by appropriate modification of the thalidomide structure, and are expected to be superior lead compounds for novel immunomodulators, anti-angiogenic agents, and anti-tumor promoting agents.
Topics: Adjuvants, Immunologic; Angiogenesis Inhibitors; Antineoplastic Agents; Drug Design; Humans; Retinoids; Structure-Activity Relationship; Thalidomide
PubMed: 12370039
DOI: 10.2174/1389557023405576