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The Cochrane Database of Systematic... Mar 2013This is an updated version of a previously published review in The Cochrane Library (2005, Issue 2) on 'Megestrol acetate for the treatment of anorexia-cachexia... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
This is an updated version of a previously published review in The Cochrane Library (2005, Issue 2) on 'Megestrol acetate for the treatment of anorexia-cachexia syndrome'. Megestrol acetate (MA) is currently used to improve appetite and to increase weight in cancer-associated anorexia. In 1993, MA was approved by the US Food and Drug Administration for the treatment of anorexia, cachexia or unexplained weight loss in patients with AIDS. The mechanism by which MA increases appetite is unknown and its effectiveness for anorexia and cachexia in neoplastic and AIDS (acquired immunodeficiency syndrome) patients is under investigation.
OBJECTIVES
To evaluate the efficacy, effectiveness and safety of MA in palliating anorexia-cachexia syndrome in patients with cancer, AIDS and other underlying pathologies.
SEARCH METHODS
We sought studies through an extensive search of electronic databases, journals, reference lists, contact with investigators and other search strategies outlined in the methods. The most recent search for this update was carried out in May 2012.
SELECTION CRITERIA
Studies were included in the review if they assessed MA compared to placebo or other drug treatments in randomised controlled trials of patients with a clinical diagnosis of anorexia-cachexia syndrome related to cancer, AIDS or any other underlying pathology.
DATA COLLECTION AND ANALYSIS
Two independent review authors conducted data extraction and evaluated methodological quality. We performed quantitative analyses using appetite and quality of life as a dichotomous variable, and analysed weight gain as continuous and dichotomous variables.
MAIN RESULTS
We included 35 trials in this update, the same number but not the same trials as in the previous version of the review. The trials comprised 3963 patients for effectiveness and 3180 for safety. Sixteen trials compared MA at different doses with placebo, seven trials compared different doses of MA with other drug treatments and 10 trials compared different doses of MA. Meta-analysis showed a benefit of MA compared with placebo, particularly with regard to appetite improvement and weight gain in cancer, AIDS and other underlying conditions, and lack of benefit in the same patients when MA was compared to other drugs. There was insufficient information to define the optimal dose of MA, but higher doses were more related to weight improvement than lower doses. Quality of life improvement in patients was seen only when comparing MA versus placebo but not other drugs in both subcategories: cancer and AIDS. Oedema, thromboembolic phenomena and deaths were more frequent in the patients treated with MA. More than 40 side effects were studied.
AUTHORS' CONCLUSIONS
This review shows that MA improves appetite and is associated with slight weight gain in cancer, AIDS and in patients with other underlying pathology. Despite the fact that these patients are receiving palliative care they should be informed of the risks involved in taking MA.
Topics: Acquired Immunodeficiency Syndrome; Anorexia; Appetite Stimulants; Cachexia; Humans; Megestrol Acetate; Neoplasms; Randomized Controlled Trials as Topic; Syndrome
PubMed: 23543530
DOI: 10.1002/14651858.CD004310.pub3 -
The American Journal of Geriatric... Jun 2020
Topics: Drug Therapy, Combination; Humans; Megestrol; Megestrol Acetate; Mental Disorders
PubMed: 32122805
DOI: 10.1016/j.jagp.2020.01.188 -
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 -
Oncology 1992Although current hormonal therapy of prostate cancer may not appear to have altered survival appreciably, there have been considerable changes that may significantly... (Review)
Review
Although current hormonal therapy of prostate cancer may not appear to have altered survival appreciably, there have been considerable changes that may significantly affect the future management of this disease. A number of new hormonal agents have been introduced that still require definition of their therapeutic efficacy. Megestrol acetate, a hormonal agent with multiple sites of action in androgen metabolism, has recently been investigated in the treatment of patients with metastatic and locally advanced disease, and in those patients whose disease progresses with other hormonal therapies. Megestrol acetate plus mini-dose diethylstilbestrol (DES) is associated with fewer side effects than standard-dose DES and has equivalent therapeutic efficacy in the treatment of patients with metastatic disease. In patients with locally advanced disease that may benefit from hormonal cytoreduction, megestrol acetate is effective and well tolerated. Megestrol acetate has a role in the palliation of patients with progressive disease despite initial hormonal therapy. Considerable controversy surrounds the therapy of carcinoma of the prostate; further studies are required to define optimal hormonal therapy.
Topics: Diethylstilbestrol; Drug Therapy, Combination; Humans; Male; Megestrol; Megestrol Acetate; Neoplasm Metastasis; Prostatic Neoplasms
PubMed: 1461622
DOI: 10.1159/000227123 -
International Journal of Nanomedicine 2006The aim is to review major clinical trials that have used megestrol acetate (MA) in the treatment of cachexia across several disease states. A review of general usage... (Review)
Review
The aim is to review major clinical trials that have used megestrol acetate (MA) in the treatment of cachexia across several disease states. A review of general usage and potential side-effects are discussed. A theory that the newly approved nanocrystal formation of MA can better deliver this potent medication for treatment will also be reviewed.
Topics: Anorexia; Cachexia; Clinical Trials as Topic; Drug Carriers; Humans; Megestrol Acetate; Nanoparticles
PubMed: 17722275
DOI: 10.2147/nano.2006.1.4.411 -
Journal of Renal Care Mar 2016Various populations are affected by chronic kidney disease (CKD), and a low dose appetite stimulant megestrol acetate (MA) is sometimes recommended in patients with CKD... (Review)
Review
BACKGROUND
Various populations are affected by chronic kidney disease (CKD), and a low dose appetite stimulant megestrol acetate (MA) is sometimes recommended in patients with CKD to ameliorate protein-energy wasting (PEW). Patients with CKD are at greater risk of developing PEW since the progression of their disease can cause decreased nutrient intake, catabolic effects, systemic inflammation and metabolic changes. Providers can detect PEW in CKD by identifying low serum levels ≤3.8 g/dl of albumin, <30 mg/dl of transthyretin, or <100 mg/dl of cholesterol. Other characteristics include BMI <22 kg/m(2) (for ≤65 years), unintentional weight loss of ≥5% in three months or ≥10% in six months, body fat percentage <10%, with muscle wasting of a reduction of ≥5% in three months or ≥10% in six months of muscle mass.
METHOD
A review of research was completed and data collected from small population-based retrospective studies to determine the effect of MA.
RESULTS
Clinical trials demonstrated the effectiveness of MA by showing increases in BMI up to 9%, albumin levels up to 1.1 g/dl, with reported protein and energy intake increases from 27% to 42%. There are potential adverse effects of using MA in CKD.
CONCLUSION
After reviewing the available literature, the benefits of using MA should be evaluated against the potential side effects. For further examination of MA's potential benefits, long-term, prospective, large clinical trials should be carried out.
Topics: Appetite Stimulants; Humans; Megestrol Acetate; Protein-Energy Malnutrition; Renal Insufficiency, Chronic; Wasting Syndrome
PubMed: 26537025
DOI: 10.1111/jorc.12138 -
Pharmacotherapy Apr 2009A rising concern among clinicians is treatment of unplanned weight loss in the elderly, especially given the predicted growth of this population over the next few... (Review)
Review
A rising concern among clinicians is treatment of unplanned weight loss in the elderly, especially given the predicted growth of this population over the next few decades. Unexpected weight loss in the geriatric patient worsens overall health outcomes. A variety of pharmacotherapeutic options are available for treatment; however, evidence underlying their use is limited, and none has gained approval from the United States Food and Drug Administration for this indication. At present, no guidelines support the choice of one agent over another. Although several drug interventions have been employed for this problem, megestrol acetate and mirtazapine are becoming increasingly used for appetite stimulation. These drugs represent two feasible options for geriatric patients because of their generally favorable adverse-effect profiles and few drug interactions, but they are often misused. In a comprehensive search of the MEDLINE and International Pharmaceutical Abstracts databases, we identified all published reports on the use of megestrol acetate or mirtazapine for the treatment of weight loss and on any adverse events associated with these drugs. Special emphasis was placed on trials performed in an elderly population. Results were conflicting, most likely because of differing study designs and small numbers of patients. Megestrol acetate and mirtazapine appear to be effective for appetite stimulation and weight gain in some settings. However, applicability of the data to elderly individuals is unclear, and adverse events reported in a few of the trials and in case reports were not benign. Therefore, the use of megestrol acetate or mirtazapine for weight loss should be thoroughly evaluated on an individual basis. Pharmacotherapy should be used only after all underlying causes of weight loss are assessed and treated.
Topics: Aged; Antidepressive Agents, Tricyclic; Appetite Stimulants; Cachexia; Case-Control Studies; Dose-Response Relationship, Drug; Drug Monitoring; Humans; Megestrol Acetate; Mianserin; Mirtazapine; Prospective Studies; Randomized Controlled Trials as Topic; Retrospective Studies; Time Factors; Wasting Syndrome; Weight Loss
PubMed: 19323618
DOI: 10.1592/phco.29.4.383 -
The Cochrane Database of Systematic... Apr 2005Megestrol acetate (MA) is currently used to improve appetite and to increase weight in cancer-associated anorexia. In 1993 MA was approved by the USA's Federal Drug... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Megestrol acetate (MA) is currently used to improve appetite and to increase weight in cancer-associated anorexia. In 1993 MA was approved by the USA's Federal Drug Administration for the treatment of anorexia, cachexia, or unexplained weight loss in patients with AIDS. The mechanism by which MA increases appetite is unknown, and its effectiveness for anorexia and cachexia in neoplastic and AIDS patients is under investigation.
OBJECTIVES
To evaluate the efficacy, effectiveness and safety of MA in palliating anorexia-cachexia syndrome in patients with cancer, AIDS and other underlying pathologies.
SEARCH STRATEGY
Studies were sought thorough an extensive search of the electronic databases, journals, reference lists, contact with investigators and other search strategies outlined in the methods. The most recent search was carried out on October 2002.
SELECTION CRITERIA
Studies were included in the review if they assessed megestrol acetate compared to placebo or other drug treatments in randomized controlled trials of patients with a clinical diagnosis of anorexia-cachexia related to cancer, AIDS or another underlying pathology.
DATA COLLECTION AND ANALYSIS
Data extraction was conducted by two independent authors, and methodological quality evaluated. Quantitative analyses were performed using appetite and quality of life as a dichotomous variable, and weight gain was analysed as continuous and dichotomous variables. Studies with more than 50% of patients lost to follow-up were excluded from the analysis.
MAIN RESULTS
Thirty trials met the inclusion criteria (4123 patients). Twenty-one trials compared MA at different doses with placebo; four compared different doses of MA versus other drugs; two compared MA with other drugs and placebo; and three compared different doses of MA. For all patient conditions, meta-analysis showed a benefit of MA compared with placebo, particularly with regard to appetite improvement and weight gain in cancer patients. Analysing quality of life, clinical and statistical heterogeneity was found and discussed. There was insufficient information to define the optimal dose of MA.
AUTHORS' CONCLUSIONS
This review demonstrates that MA improves appetite and weight gain in patients with cancer. No overall conclusion about quality of life (QOL) could be drawn due to heterogeneity. The small number of patients, methodological shortcomings and poor reporting have not allowed us to recommend megestrol acetate in AIDS patients or with other underlying pathologies.
Topics: Acquired Immunodeficiency Syndrome; Anorexia; Appetite Stimulants; Cachexia; Humans; Megestrol Acetate; Neoplasms; Randomized Controlled Trials as Topic; Syndrome
PubMed: 15846706
DOI: 10.1002/14651858.CD004310.pub2 -
Steroids May 2020Drug repurposing or repositioning i.e.; identifying new indications for existing drugs have recently accelerated the process of drug discovery and development. Megestrol...
AIMS
Drug repurposing or repositioning i.e.; identifying new indications for existing drugs have recently accelerated the process of drug discovery and development. Megestrol acetate (1) is a well-known progestin. It is commonly used as an appetite stimulant, and also in the treatment of breast, and endometrial cancers. The aim of this study is to investigate the effect of megestrol acetate (1) in osteoblast differentiation, and to determine the possible mechanism involved in megestrol acetate (1) induced osteoblast differentiation.
MAIN METHODS
Cytotoxicity of different steroidal drugs was evaluated using MTT assay. Alkaline phosphatase (ALP) activity was also determined, and alizarin red S (ARS) staining was performed to measure extracellular mineralization. Osteogenic protein levels were determined using Western blot analysis.
KEY FINDINGS
Results of the current study indicated that the megestrol acetate (1) enhanced the proliferation and differentiation of osteoblast cells at 1, 0.2, and 0.04 µM. This stimulatory effect of the megestrol acetate (1) was more prominent at 0.2 µM for cell proliferation, while the maximum cell differentiation (ALPase activity, and calcification) was observed at 0.04 μM. Western blot analysis also showed that megestrol acetate (1) altered the expression of bone morphogenic protein-2 (BMP2), p38, and pJNK proteins. Hence, only moderate doses of MGA (1) can enhance osteoblast proliferation and differentiation.
SIGNIFICANCE
Our results identified that megestrol acetate (1) could be a potential lead for further research towards bone fragility related disorders.
Topics: 3T3-L1 Cells; Animals; Antineoplastic Agents, Hormonal; Cell Differentiation; Cell Proliferation; Cell Survival; Cells, Cultured; Dose-Response Relationship, Drug; Megestrol Acetate; Mice; Molecular Conformation; Osteoblasts; Structure-Activity Relationship
PubMed: 32084501
DOI: 10.1016/j.steroids.2020.108607 -
The Journal of Family Practice Feb 2018No. Megestrol acetate (MA) is neither safe nor effective for stimulating appetite in malnourished nursing home residents. It increases the risk of deep vein thrombosis... (Review)
Review
No. Megestrol acetate (MA) is neither safe nor effective for stimulating appetite in malnourished nursing home residents. It increases the risk of deep vein thrombosis (strength of recommendation [SOR]: C, 2 retrospective chart reviews), but isn't associated with other new or worsening events or disorders (SOR: B, single randomized controlled trial [RCT]). Over a 25-week period, MA wasn't associated with increased mortality (SOR: B, single RCT). After 44 months, however, MA-treated patients showed decreased median survival (SOR: B, single case-control study). Consistent, meaningful weight gain was not observed with MA treatment (SOR: B, single case-control study, single RCT, 2 retrospective chart reviews, single prospective case-series).
Topics: Appetite Stimulants; Humans; Malnutrition; Megestrol Acetate; Nursing Homes; Risk Factors; Venous Thrombosis
PubMed: 29400904
DOI: No ID Found