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Nephrology Nursing Journal : Journal of... 2021Nutritional and metabolic abnormalities, or protein energy wasting, is a common complication of chronic kidney disease, leading to significant morbidity and mortality.... (Review)
Review
Nutritional and metabolic abnormalities, or protein energy wasting, is a common complication of chronic kidney disease, leading to significant morbidity and mortality. The cause of these abnormalities is multifactorial, and therefore, difficult to treat. The International Society of Renal Nutrition and Metabolism suggests appetite stimulants, including megestrol, dronabinol, mirtazapine, and cyproheptadine, as adjunctive treatment options in addition to parenteral or oral nutritional supplementation. This article reviews the evidence for use of these drugs as appetite stimulants and discusses their use in patients with chronic kidney disease.
Topics: Appetite Stimulants; Humans; Nutritional Status; Renal Dialysis; Renal Insufficiency, Chronic
PubMed: 34286938
DOI: No ID Found -
Cancers Oct 2023Granular cell tumors (GCT) represent 0.5% of all soft tissue sarcomas (STS), and when metastatic, they exhibit aggressive behavior and determine limited survival.... (Review)
Review
Granular cell tumors (GCT) represent 0.5% of all soft tissue sarcomas (STS), and when metastatic, they exhibit aggressive behavior and determine limited survival. Metastatic GCTs are relatively chemo-resistant; however, there is growing evidence of the benefit of using pazopanib and other targeted therapies in this histology. This is a review of the role of pazopanib and other targeted therapies in the treatment of GCTs, along with some insights on pathology and molecular biology described in GCTs. From 256 articles found in our search, 10 case-report articles met the inclusion criteria. Pazopanib was the most employed systemic therapy. The median reported time on therapy with pazopanib was seven months. Eight out of ten patients (80%) experienced disease control with pazopanib, while four out of ten (40%) patients achieved an objective RECIST response. Molecular studies suggested that antitumoral effects of pazopanib in GCT might be due to a loss-of-function of genes which consequently enhance signaling through several molecular pathways, such as SFKs, STAT5a/b, and PDGFR-β. Other reported targeted therapies for malignant GCTs included pazopanib in combination with crizotinib, which showed disease control for four months in one patient, and a PI3K inhibitor which achieved disease control for nine months in another patient. Dasatinib and megestrol were ineffective in two other different patients. Pazopanib has been demonstrated to be active in advanced GCTs and may be considered as a preferable treatment option.
PubMed: 37958362
DOI: 10.3390/cancers15215187 -
Journal of the American Medical... Dec 2014Body wasting in the context of chronic illness is associated with reduced quality of life and impaired survival. Recent clinical trials have investigated different... (Review)
Review
Body wasting in the context of chronic illness is associated with reduced quality of life and impaired survival. Recent clinical trials have investigated different approaches to improve patients' skeletal muscle mass and strength, exercise capacity, and survival in the context of cachexia and body wasting, many of them in patients with cancer. The aim of this article was to summarize clinical trials published over the past 2 years. Therapeutic approaches discussed include appetite stimulants, such as megestrol acetate, L-carnitine, or melatonin, anti-inflammatory drugs, such as thalidomide, pentoxyphylline, or a monoclonal antibody against interleukin-1α as well as ghrelin and the ghrelin agonist anamorelin; nutritional support, and anabolics, such as enobosarm and testosterone.
Topics: Anabolic Agents; Anti-Inflammatory Agents; Antibodies, Monoclonal; Appetite Stimulants; Cachexia; Ghrelin; Humans; Muscle Strength; Muscle, Skeletal; Neoplasms; Nutritional Support; Quality of Life; Survival Analysis
PubMed: 25455531
DOI: 10.1016/j.jamda.2014.09.007 -
Contemporary Oncology (Poznan, Poland) 2018Hepatocellular carcinoma (HCC) is one of the leading causes of cancer death worldwide. There is as yet no standard therapy for inoperable HCC. We aimed to systematically... (Review)
Review
INTRODUCTION
Hepatocellular carcinoma (HCC) is one of the leading causes of cancer death worldwide. There is as yet no standard therapy for inoperable HCC. We aimed to systematically review all health-related evidence regarding the effectiveness and safety of megestrol in HCC patients.
MATERIAL AND METHODS
We conducted a systematic computerised search in PubMed, Scopus, Web of Science, Embase, and Cochrane CENTRAL. All original human studies reporting the efficacy of megestrol in HCC patients were included in our review.
RESULTS
Six studies including 357 patients were finally eligible. The overall mean survival time of 87 megestrol-treated patients, was 9.187 (95% CI 1.134-17.239) months. Eight patients had tumour size enlargement, and eight patients had tumour size reduction. From three studies including 76 patients, 42 patients reported having improvement of appetite and food intake after receiving megestrol. Diverse adverse events were noticed between studies; however, they were tolerable in most of the studies.
CONCLUSIONS
To summarise, no conclusive evidence should be declared regarding the effectiveness of megestrol in patients with inoperable HCC. However, previous studies have shown promising results at the level of prolonging the survival rate, tumour size reduction, and improving the quality of life. Therefore, we recommend that future research studies must examine the role of megestrol in large-population, randomised studies.
PubMed: 30783383
DOI: 10.5114/wo.2018.82641 -
Annals of Palliative Medicine Jan 2019Cancer cachexia (CC) is common in advanced cancer and is accompanied by negative effects on health-related quality of life (HRQOL). However, methods to identify the... (Review)
Review
Cancer cachexia (CC) is common in advanced cancer and is accompanied by negative effects on health-related quality of life (HRQOL). However, methods to identify the impact of CC on HRQOL are limited. Single questionnaire items may provide insight on the effect of CC on HRQOL. Specifically, the use of "feeling of wellbeing" (FWB) on the Edmonton Symptom Assessment System (ESAS) questionnaire and the Distress Thermometer (DT) have been explored. Assessing how these two surrogate measures of HRQOL are impacted among CC stages and what drives these negative effects may allow for focused treatments. Five-hundred and twelve patients referred to a Cancer Rehabilitation Program completed the ESAS, with the question on FWB and the DT at baseline. Patients were separated into CC stages: non-cachexia (NC), pre-cachexia (PC), cachexia (C), refractory cachexia (RC). A mixed model ANOVA with post hoc Tukey adjustment was used to compare means of FWB and distress among the CC stages. To understand what was driving the differences between CC stages, a robust regression model was created with either distress or FWB as the outcome measure, dependent on the other measures in ESAS, age and sex. Finally, the use of cannabinoids in treating appetite loss was examined, as it has a detrimental effect on FWB; 54 patients underwent cannabinoid treatment for appetite loss within a community-based, physician-lead, medical cannabis clinic. A t-test to assess changes in ESAS appetite score after 3 months of cannabinoid treatment was examined. RC patients had a significantly poorer sense of wellbeing than the other cachexia stages (RC: 6.07±0.33). Significant differences in distress were identified between RC patients and those with NC and C, but not with PC (RC: 4.87±0.38, NC: 3.35±0.26, PC: 4.11±0.30, C: 3.60±0.28). FWB was negatively affected by worsening appetite in all CC stages except NC (PC: 0.19±0.08, P=0.022; C: 0.26±0.06, P<0.001; RC: 0.23±0.08, P=0.007). ESAS score for lack of appetite significantly improved between baseline (5.07±3.21) and follow-up (3.56±3.15, P=0.003) after cannabinoid treatment, with no significant difference in weight (baseline: 70.7±14.6 kg, 3-month follow-up: 71.0±14.8 kg). Future research should validate both multidimensional and single-item tools to measure HRQOL in patients at different stages of CC. Improvement of HRQOL via appetite stimulation, may be achieved through a multidisciplinary approach, which includes cannabinoid therapy.
Topics: Adrenal Cortex Hormones; Anorexia; Appetite Stimulants; Cachexia; Cannabinoids; Cyproheptadine; Female; Health Status; Humans; Hydrazines; Male; Megestrol Acetate; Middle Aged; Neoplasms; Oligopeptides; Quality of Life; Serotonin Antagonists; Severity of Illness Index; Stress, Psychological; Surveys and Questionnaires
PubMed: 30525763
DOI: 10.21037/apm.2018.08.04 -
Medicina Clinica Mar 2022
Topics: Adolescent; Adrenal Insufficiency; Child; Humans; Hydrocortisone; Megestrol; Megestrol Acetate
PubMed: 34074479
DOI: 10.1016/j.medcli.2021.04.019 -
The American Journal of Geriatric... Jun 2020To analyze the risk of megestrol, a glucocorticoid and progesterone receptor agonist used to enhance appetite, on the development of a new psychiatric diagnosis. (Comparative Study)
Comparative Study
OBJECTIVE
To analyze the risk of megestrol, a glucocorticoid and progesterone receptor agonist used to enhance appetite, on the development of a new psychiatric diagnosis.
DESIGN AND PARTICIPANTS
Deidentified data of megestrol (n = 706) and propensity score-matched comparison (age, gender, and body mass index) patients (n = 2,118) from January 1, 2001 to June 30, 2018 were obtained from the UT Southwestern patient database. Data were analyzed using a series of conditional binary logistic regressions controlling for comorbidities, pre-existing psychiatric disorders, and number of patient encounters.
SETTING
A large academic medical center database of megestrol-treated patients and matched comparison patients was used.
MEASUREMENTS AND RESULTS
The regression model showed that megestrol was significantly associated with developing a new psychiatric diagnosis (B = 1.28, Wald χ = 83.12, odds ratio [OR] = 3.60, p <0.001). In subgroup analyses, development of cognitive (B = 2.42, Wald χ = 16.09, OR = 11.30, p <0.001), mood (B = 1.31, Wald χ = 40.38, OR = 3.70, p <0.001), and anxiety (B = 1.72, Wald χ = 45.28, OR = 5.60, p <0.001) disorders were also associated with megestrol use.
CONCLUSIONS
Patients taking megestrol were significantly more likely to develop a new psychiatric diagnosis than comparison patients. Highest risks were associated with the development of cognitive diagnoses. The findings suggest that megestrol, like other glucocorticoid agonists, is associated with an increased risk of developing a psychiatric disorder. This risk should be considered when determining the risk-to-benefit ratio of megestrol use in patients.
Topics: Aged; Anxiety Disorders; Comorbidity; Databases, Factual; Female; Glucocorticoids; Humans; Logistic Models; Male; Megestrol; Middle Aged; Psychoses, Substance-Induced; Risk Factors; Texas
PubMed: 32037291
DOI: 10.1016/j.jagp.2020.01.003 -
Kidney Research and Clinical Practice Mar 2024Inflammation, metabolic acidosis, renin-angiotensin system activation, insulin resistance, and impaired perfusion to skeletal muscles, among others, are possible causes...
Inflammation, metabolic acidosis, renin-angiotensin system activation, insulin resistance, and impaired perfusion to skeletal muscles, among others, are possible causes of uremic sarcopenia. These conditions induce the activation of the nuclear factor-kappa B and mitogen-activated protein kinase pathways, adenosine triphosphate ubiquitin-proteasome system, and reactive oxygen species system, resulting in protein catabolism. Strategies for the prevention and treatment of sarcopenia in chronic kidney disease (CKD) are aerobic and resistance exercises along with nutritional interventions. Anabolic hormones have shown beneficial effects. Megestrol acetate increased weight, protein catabolic rate, and albumin concentration, and it increased intracellular water component and muscle mass. Vitamin D supplementation showed improvement in physical function, muscle strength, and muscle mass. Correction of metabolic acidosis showed an increase in protein intake, serum albumin levels, body weight, and mid-arm circumference. The kidney- gut-muscle axis indicates that dysbiosis and changes in gut-derived uremic toxins and short-chain fatty acids affect muscle mass, composition, strength, and functional capacity. Biotic supplements, AST-120 administration, hemodiafiltration, and preservation of residual renal function are alleged to reduce uremic toxins, including indoxyl sulfate (IS) and p-cresyl sulfate (PCS). Synbiotics reversed the microbiota change in CKD patients and decreased uremic toxins. AST-120 administration changed the overall gut microbiota composition in CKD. AST-120 prevented IS and PCS tissue accumulation, ameliorated muscle atrophy, improved exercise capacity and mitochondrial biogenesis, restored epithelial tight junction proteins, and reduced plasma endotoxin levels and markers of oxidative stress and inflammation. In a human study, the addition of AST-120 to standard treatment had modest beneficial effects on gait speed change and quality of life.
PubMed: 38389147
DOI: 10.23876/j.krcp.23.094 -
Cells Mar 2022Cachexia may be caused by congestive heart failure, and it is then called cardiac cachexia, which leads to increased morbidity and mortality. Cardiac cachexia also... (Review)
Review
Cachexia may be caused by congestive heart failure, and it is then called cardiac cachexia, which leads to increased morbidity and mortality. Cardiac cachexia also worsens skeletal muscle degradation. Cardiac cachexia is the loss of edema-free muscle mass with or without affecting fat tissue. It is mainly caused by a loss of balance between protein synthesis and degradation, or it may result from intestinal malabsorption. The loss of balance in protein synthesis and degradation may be the consequence of altered endocrine mediators such as insulin, insulin-like growth factor 1, leptin, ghrelin, melanocortin, growth hormone and neuropeptide Y. In contrast to many other health problems, fat accumulation in the heart is protective in this condition. Fat in the heart can be divided into epicardial, myocardial and cardiac steatosis. In this review, we describe and discuss these topics, pointing out the interconnection between heart failure and cardiac cachexia and the protective role of cardiac obesity. We also set the basis for possible screening methods that may allow for a timely diagnosis of cardiac cachexia, since there is still no cure for this condition. Several therapeutic procedures are discussed including exercise, nutritional proposals, myostatin antibodies, ghrelin, anabolic steroids, anti-inflammatory substances, beta-adrenergic agonists, medroxyprogesterone acetate, megestrol acetate, cannabinoids, statins, thalidomide, proteasome inhibitors and pentoxifylline. However, to this date, there is no cure for cachexia.
Topics: Cachexia; Ghrelin; Heart; Heart Failure; Humans; Obesity
PubMed: 35326490
DOI: 10.3390/cells11061039 -
Cancer Chemotherapy and Pharmacology Dec 2021Megestrol acetate is a synthetic progestogen used to treat some cancers and cancer-associated cachexia, but its potential interactions with other drugs are not well...
PURPOSE
Megestrol acetate is a synthetic progestogen used to treat some cancers and cancer-associated cachexia, but its potential interactions with other drugs are not well known. This study aims to determine the regulation of drug metabolizing enzymes by megestrol acetate.
METHODS
Primary human hepatocytes were treated and analyzed by PCR array to identify genes involved in drug metabolism that are impacted by megestrol acetate. P450 3A4 (CYP3A4) reporter gene assay and HPLC analyses of nifedipine metabolites were used to determine CYP3A4 gene expression and activities. Competitive ligand binding assay was used to determine the affinity of megestrol acetate toward human pregnane x receptor (hPXR). Electrophoretic mobility shift assay and mammalian two hybrid assay were used to determine the mechanism of megestrol to activate hPXR.
RESULTS
The levels and activities of CYP3A4 were significantly induced (> 4-folds) by megestrol acetate in human hepatocytes and HepG2 cells. Megestrol treatment induced CYP3A4 through the activation of hPXR, a ligand-activated transcription factor that plays a role in drug metabolism and transport. Other tested nuclear receptors showed no response. The mechanism studies showed that megestrol activated hPXR by binding to the ligand binding domain (LBD) of hPXR and increasing the recruitment of the cofactors such as steroid receptor cofactor (SRC-1).
CONCLUSION
The results suggest that megestrol acetate is a specific inducer of CYP3A4 mediated by hPXR and therefore has the potential to cause drug interactions, especially in the co-administration with drugs that are substrates of CYP3A4.
Topics: Antineoplastic Agents, Hormonal; Cytochrome P-450 CYP3A; Cytochrome P-450 CYP3A Inducers; Drug Interactions; Hep G2 Cells; Hepatocytes; Humans; Megestrol Acetate; Pregnane X Receptor
PubMed: 34524495
DOI: 10.1007/s00280-021-04352-9