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Cancers Apr 2022Endometrial cancer (EC) rarely develops in young women. Most cases are associated with known risk factors: BMI > 30, history of Polycystic Ovary Syndrome (PCOs), and... (Review)
Review
Endometrial cancer (EC) rarely develops in young women. Most cases are associated with known risk factors: BMI > 30, history of Polycystic Ovary Syndrome (PCOs), and race differentiation. The molecular EC classification based on The Cancer Genome Atlas Research Network divides these heterogeneous cancers into four types: Polymerase Epsilon Mutation (POLE), Microsatellite Instability (MSI), Copy Number Low (CNL), and Copy Number High (CNH). This division was introduced to allow for early assessment of neoplastic changes and clinical management, including targeted therapies. The basic technique for imaging endometrium changes is transvaginal sonography. Hysteroscopy is the standard for obtaining endometrial material for histological evaluation. The MRI result permits assessment of the extent of EC cancer infiltration. In young women who want to preserve fertility, apart from surgery, conservative management is often implemented after strict selection based on clinical and pathological data. This pharmacological treatment involves the administration of progestogens MPA (medroxyprogesterone acetate) and MA (megestrol acetate). The use of metformin may increase the effectiveness of such treatment. An alternative option is to apply progestogens locally—via the levonorgestrel-releasing intrauterine device. In addition to pharmacological treatment, hysteroscopic resection may be used—part of the uterine muscle adjacent to the pathologically changed endometrium may also undergo resection. An alternative is the administration of estrogen receptor modulators (e.g., SERMs) or aromatase inhibitors, or GnRH agonists.
PubMed: 35454829
DOI: 10.3390/cancers14081922 -
Pharmaceuticals (Basel, Switzerland) Feb 2022Cisplatin is a well-known chemotherapeutic agent used to treat various types of cancers; however, it can also induce anorexia, which results in reduced food intake, loss... (Review)
Review
Cisplatin is a well-known chemotherapeutic agent used to treat various types of cancers; however, it can also induce anorexia, which results in reduced food intake, loss of body weight, and lower quality of life. Although drugs such as megestrol acetate and cyproheptadine are used to decrease this severe feeding disorder, they can also induce side effects, such as diarrhea and somnolence, which limit their widespread use. Various types of herbal medicines have long been used to prevent and treat numerous gastrointestinal tract diseases; however, to date, no study has been conducted to analyze and summarize their effects on cisplatin-induced anorexia. In this paper, we analyze 12 animal studies that used either a single herbal medicine extract or mixtures thereof to decrease cisplatin-induced anorexia. Among the herbal medicines, Ginseng Radix was the most used, as it was included in seven studies, whereas both Glycyrrhizae Radix et Rhizoma and Angelicae Gigantis Radix were used in four studies. As for the mechanisms of action, the roles of serotonin and its receptors, cytokines, white blood cells, ghrelin, and leptin were investigated. Based on these results, we suggest that herbal medicines could be considered a useful treatment method for cisplatin-induced anorexia.
PubMed: 35215322
DOI: 10.3390/ph15020208 -
Molecules (Basel, Switzerland) Mar 2021The aim of this work is to present an approach to enhance the dissolution of progestin medication, megestrol acetate (also known as MEGACE), for improving the...
The aim of this work is to present an approach to enhance the dissolution of progestin medication, megestrol acetate (also known as MEGACE), for improving the dissolution rate and kinetic solubility by incorporating nano graphene oxide (nGO). An antisolvent precipitation process was investigated for nGO-drug composite preparation, where prepared composites showed crystalline properties that were similar to the pure drug but enhanced aqueous dispersibility and colloidal stability. To validate the efficient release profile of composite, in vitro dissolution testing was carried out using United States Pharmacopeia, USP-42 paddle method, with gastric pH (1.4) and intestinal pH (6.5) solutions to mimic in vivo conditions. Pure MA is practically insoluble (2 µg/mL at 37 °C). With the incorporation of nGO, it was possible to dissolve nearly 100% in the assay. With the incorporation of 1.0% of nGO, the time required to dissolve 50% and 80% of drug, namely T and T, decreased from 138.0 min to 27.0 min, and the drug did not dissolve for 97.0 min in gastric media, respectively. Additionally, studies done in intestinal media have revealed T did not dissolve for 92.0 min. This work shows promise in incorporating functionalized nanoparticles into the crystal lattice of poorly soluble drugs to improve dissolution rate.
Topics: Biological Availability; Chemistry, Pharmaceutical; Drug Compounding; Excipients; Graphite; Hydrophobic and Hydrophilic Interactions; Megestrol Acetate; Nanoparticles; Solubility
PubMed: 33807401
DOI: 10.3390/molecules26071972 -
The Cochrane Database of Systematic... Sep 2022Chronic loss of appetite in cystic fibrosis concerns both individuals and families. Appetite stimulants have been used to help cystic fibrosis patients with chronic... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Chronic loss of appetite in cystic fibrosis concerns both individuals and families. Appetite stimulants have been used to help cystic fibrosis patients with chronic anorexia attain optimal body mass index (BMI) and nutritional status. However, these may have adverse effects on clinical status. This is an updated version of the original review.
OBJECTIVES
To systematically search for and evaluate the evidence on the beneficial effects of appetite stimulants in the management of cystic fibrosis-related anorexia and synthesise reports of any side effects.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Cystic Fibrosis Trials Register and online trials registries; handsearched reference lists; and contacted local and international experts to identify relevant trials. Last search of the Cystic Fibrosis Trials Register: 23 May 2022. Last search of online trial registries: 10 May 2022.
SELECTION CRITERIA
Randomised and quasi-randomised controlled trials of appetite stimulants compared to placebo, control, no treatment or different appetite stimulants, or to the same appetite stimulants at different doses or regimens for at least one month in adults and children with cystic fibrosis.
DATA COLLECTION AND ANALYSIS
Review authors independently extracted data and assessed risk of bias of the included trials. We used the GRADE approach to assess the certainty of the evidence and performed meta-analyses.
MAIN RESULTS
We included four trials (70 participants) comparing appetite stimulants (cyproheptadine hydrochloride and megestrol acetate) to placebo; the numbers of adults or children within each trial were not always reported. We assessed the certainty of evidence as low due to the small number of participants, incomplete or selective outcome reporting, and unclear risk of selection bias. Regarding our primary outcomes, a meta-analysis of two trials (42 participants) showed that appetite stimulants may produce a larger increase in weight (kg) at three months (mean difference (MD) 1.25 kg, 95% confidence interval (Cl) 0.45 to 2.05), and one trial (17 participants) showed a similar result at six months (MD 3.80 kg, 95% CI 1.27 to 6.33) (both low-certainty evidence). Results also showed that weight z score may increase with appetite stimulants compared to placebo at three months (MD 0.61, 95% CI 0.29 to 0.93; 3 studies; 40 participants; P < 0.001) and at six months (MD 0.74, 95% CI 0.26 to 1.22; 1 trial; 17 participants). There was no evidence of a difference in effect between cyproheptadine hydrochloride and megestrol acetate for either outcome. Only one trial (25 participants) reported analysable data for body composition (BMI), with results favouring cyproheptadine hydrochloride compared to placebo; a further trial (16 participants) narratively agreed with this result. All four trials reported on lung function at durations ranging from two to nine months. Considering analysable data, two trials (42 participants) found that appetite stimulants may make little or no difference in forced expiratory volume at one second (FEV) % predicted at three months, and one trial (17 participants) found similar results at six months. Two further three-month trials narratively agreed with these results. Limited information was reported for secondary outcomes. Two trials (23 participants) reported results showing that appetite stimulants may increase appetite compared to placebo at three months (odds ratio 45.25, 95% CI 3.57 to 573.33; low-certainty evidence). Only one study reported on quality of life, finding that cyproheptadine reduced fatigue in two participants compared with none with placebo. One study (25 participants) found no difference in energy intake between appetite stimulant or placebo at three months. Insufficient reporting of adverse effects prevented a full determination of their impact. Two studies (33 participants) narratively reported similar requirements for additional antibiotics between appetite stimulants and placebo at three months. AUTHORS' CONCLUSIONS: At six months in adults and children, appetite stimulants improved only two of the outcomes of this review: weight (or weight z score) and subjectively reported appetite. Insufficient reporting of side effects prevented a full determination of their impact. Whilst the data may suggest the potential use of appetite stimulants in treating anorexia in adults and children with cystic fibrosis, this is based upon low-certainty evidence from a small number of trials, therefore firm conclusions cannot be drawn. Clinicians need to be aware of the potential adverse effects of appetite stimulants and actively monitor any individuals prescribed these medications accordingly. Research is required to determine meaningful surrogate measures for appetite and to define what constitutes quality weight gain. Future trials of appetite stimulants should use a validated measure of symptoms including a disease-specific instrument for measuring poor appetite. This review highlights the need for multicentred, adequately powered, and well-designed trials to evaluate agents to safely increase appetite in people with cystic fibrosis and to establish the optimal mode of treatment.
Topics: Adult; Anorexia; Anti-Bacterial Agents; Appetite Stimulants; Child; Cyproheptadine; Cystic Fibrosis; Humans; Megestrol Acetate; Quality of Life
PubMed: 36149378
DOI: 10.1002/14651858.CD008190.pub3 -
Sovremennye Tekhnologii V Meditsine 2021This review summarizes the current opinions on the mechanisms of action of nuclear, mitochondrial, and membrane progesterone receptors. The main aspects of the... (Review)
Review
This review summarizes the current opinions on the mechanisms of action of nuclear, mitochondrial, and membrane progesterone receptors. The main aspects of the pharmacological action of progestins have been studied. Data on the clinical use of gestagens by nosological groups are presented. Particular attention is paid to progesterone, megestrol acetate, medroxyprogesterone acetate due to broadening of their spectrum of action. The possibilities of using gestagens as neuroprotectors, immunomodulators, and chemosensitizers are considered.
Topics: Medroxyprogesterone; Medroxyprogesterone Acetate; Megestrol; Progesterone; Progestins
PubMed: 34513071
DOI: 10.17691/stm2021.13.1.11 -
Experimental Biology and Medicine... Nov 2021Megestrol acetate is a common and efficient anticancer progesterone. To explore the activity and the therapeutic mechanisms of megestrol acetate in endometrial cancer,...
Megestrol acetate is a common and efficient anticancer progesterone. To explore the activity and the therapeutic mechanisms of megestrol acetate in endometrial cancer, human endometrial cancer cell lines Ishikawa and HHUA overexpressing progesterone receptor A (PR-A) and progesterone receptor B (PR-B) were treated with megestrol acetate. Cell viability, apoptosis, cycle arrest, and senescence, as well as the expressions of p21 and p16, two hallmarks of cellular senescence, were evaluated. Compared with the control, >10 nmol/L megestrol acetate treatment could significantly reduce endometrial cancer cell growth, and induce the irreversible G1 arrest and cell senescence. The expression of cyclin D1 in megestrol acetate treated cells was downregulated, while the expressions of p21 and p16 were upregulated via PR-B isoform. FOXO1 inhibitor AS1842856 could significantly abrogate megestrol acetate-induced cell senescence, suggesting that FOXO1 was involved in megestrol acetate/PR-B axis. These findings may provide a new understanding for the treatment of human endometrial cancer.
Topics: Antineoplastic Agents, Hormonal; Blotting, Western; Cell Cycle; Cell Line, Tumor; Cellular Senescence; Endometrial Neoplasms; Female; Forkhead Box Protein O1; Humans; Megestrol; Receptors, Progesterone; Signal Transduction
PubMed: 34233525
DOI: 10.1177/15353702211026566 -
Journal of Clinical Medicine Jun 2022Cancer-related anorexia/cachexia is known to be associated with worsened quality of life and survival; however, limited treatment options exist. Although megestrol... (Review)
Review
Cancer-related anorexia/cachexia is known to be associated with worsened quality of life and survival; however, limited treatment options exist. Although megestrol acetate (MA) is often used off-label to stimulate appetite and improve anorexia/cachexia in patients with advanced cancers, the benefits are controversial. The present meta-analysis aimed to better elucidate the clinical benefits of MA in patients with cancer-related anorexia/cachexia. A systematic search of PubMed, EMBASE, OVID Medline, Clinicaltrials.gov, and Google Scholar databases found 23 clinical trials examining the use of MA in cancer-related anorexia. The available randomized, controlled trials were appraised using Version 2 of the Cochrane risk-of-bias tool (RoB 2) and they had moderate-to-high risk of bias. A total of eight studies provided sufficient data on weight change for meta-analysis. The studies were divided into high-dose treatment (>320 mg/day) and low-dose treatment (≤320 mg/day). The overall pooled mean change in weight among cancer patients treated with MA, regardless of dosage was 0.75 kg (95% CI = −1.64 to 3.15, τ2 = 9.35, I2 = 96%). Patients who received high-dose MA tended to have weight loss rather than weight gain. There were insufficient studies to perform a meta-analysis for the change in tricep skinfold, midarm circumference, or quality of life measures. MA was generally well-tolerated, except for a clear thromboembolic risk, especially with higher doses. On balance, MA did not appear to be effective in providing the symptomatic improvement of anorexia/cachexia in patients with advanced cancer.
PubMed: 35807039
DOI: 10.3390/jcm11133756 -
Cancers Sep 2023(1) Background: The standard first-line therapy for advanced adrenocortical carcinoma (ACC) is represented by EDP-M (etoposide, doxorubicin, cisplatin + mitotane)....
Feasibility and Activity of Megestrol Acetate in Addition to Etoposide, Doxorubicin, Cisplatin, and Mitotane as First-Line Therapy in Patients with Metastatic/Unresectable Adrenocortical Carcinoma with Low Performance Status.
(1) Background: The standard first-line therapy for advanced adrenocortical carcinoma (ACC) is represented by EDP-M (etoposide, doxorubicin, cisplatin + mitotane). Progestins have shown cytotoxic activity both in vitro and in vivo on ACC; better EDP-M tolerability and efficacy have been hypnotized due to the association with progestins. (2) Methods: The feasibility and tolerability of EDP-M combined with oral megestrol acetate (EDP-MM) were tested in 24 patients (pts) affected by metastatic ACC with a low performance status (PS); the case group was compared with a 48 pts control group according to the propensity score. The secondary objectives were clinical benefit rate (CBR), progression-free survival (PFS), and overall survival (OS). (3) Results: Thirteen pts (54.2%) in the EDP-MM population experienced progestin-related toxicities; in particular, five pts experienced vaginal bleeding (20.8%); four pts experienced weight gain (16.7%); and thromboembolic events, worsening of hypertension, skin rashes, and hyperglycemia were registered in one patient each (4.2%). This led to the discontinuation of megestrol acetate in four pts (16.7%). EDP-M-related toxicities were similar in both groups. No differences in PFS and OS curves were observed; the CBR was 75.0% and 60.4%, respectively. (4) Conclusions: The association of EDP-M + megestrol acetate in ACC pts with a low PS is feasible and well tolerated; its efficacy appeared to be non-inferior to EDP-M administered to pts with a good PS.
PubMed: 37760461
DOI: 10.3390/cancers15184491 -
BioMed Research International 2022Endometrial cancer (EC) is one of the most common gynecologic malignancy, mostly in postmenopausal women. The gold standard treatment for EC is surgery, but in the early... (Review)
Review
BACKGROUND
Endometrial cancer (EC) is one of the most common gynecologic malignancy, mostly in postmenopausal women. The gold standard treatment for EC is surgery, but in the early stages, it is possible to opt for conservative treatment. In the last decade, different clinical and pathological markers have been studied to identify women who respond to conservative treatment. A lot of immunohistochemical markers have been evaluated to predict response to progestin treatment, even if their usefulness is still unclear; the prognosis of this neoplasm depends on tumor stage, and a specific therapeutic protocol is set according to the stage of the disease.
OBJECTIVE
(1) To provide an overview of the conservative management of Stage 1A Grade (G) 2 endometrioid EC (FIGO) and the oncological and reproductive outcomes related; (2) to describe the molecular alterations before and after progestin therapy in patients undergoing conservative treatment.
MATERIALS AND METHODS
A systematic computerized search of the literature was performed in the main electronic databases (MEDLINE, Embase, Web of Science, PubMed, and Cochrane Library), from 2010 to September 2021, in order to evaluate the oncological and reproductive outcomes in patients with G2 stage IA EC who ask for fertility-sparing treatment. The expression of several immunohistochemical markers was evaluated in pretreatment phase and during the follow-up in relation to response to hormonal therapy. Only scientific publications in English were included. The risk of bias assessment was performed. Review authors' judgments were categorized as "low risk," "high risk," or "unclear risk" of bias.
RESULTS
Twelve articles were included in the study: 7 observational studies and 5 case series/reports. Eighty-four patients who took progestins (megestrol acetate, medroxyprogesterone acetate, and/or levonorgestrel-releasing intrauterine devices) were analyzed. The publication bias analysis turned out to be "low." 54/84 patients had a complete response, 23/84 patients underwent radical surgery, and 20/84 had a relapse after conservative treatment. Twenty-two patients had a pregnancy. The length of follow-up was variable, from 6 to 142 months according to the different studies analyzed. Several clinical and pathological markers have been studied to identify women who do not respond to conservative treatment: PR and ER were the most studied predictive markers, in particular PR appeared as the most promising; MMR, SPAG9, Ki67, and Nrf2-survivin pathway provided good results with a significant association with a good response to progestin therapy. However, no reliable predictive markers are currently available to be used in clinical practice.
CONCLUSIONS
The conservative treatment may be an option for patients with stage IA G2 EEC who desire to preserve their fertility. The immunohistochemical markers evaluation looks promising in predicting response to conservative treatment. Further large series and randomized clinical trials are needed to confirm these results.
Topics: Adaptor Proteins, Signal Transducing; Antineoplastic Agents, Hormonal; Carcinoma, Endometrioid; Endometrial Neoplasms; Female; Fertility Preservation; Humans; Ki-67 Antigen; Levonorgestrel; Medroxyprogesterone Acetate; Megestrol Acetate; NF-E2-Related Factor 2; Neoplasm Recurrence, Local; Pregnancy; Progestins; Survivin
PubMed: 36203482
DOI: 10.1155/2022/4070368 -
Annals of Translational Medicine Oct 2022A reasonable and effective control of chemotherapy-induced nausea and vomiting (CINV) plays an important role in the comprehensive treatment of cancer. Megestrol belongs...
Megestrol acetate dispersible tablets with a 5-HT3 receptor antagonist and dexamethasone 5-HT3 receptor antagonist plus dexamethasone, can better control chemotherapy-induced nausea and vomiting: a randomized controlled study.
BACKGROUND
A reasonable and effective control of chemotherapy-induced nausea and vomiting (CINV) plays an important role in the comprehensive treatment of cancer. Megestrol belongs to the 17α-hydroxyprogesterone derivative and is a highly effective synthetic progesterone. Recorded in the instructions may improve appetite and cachexia in patients with advanced tumors. In recent years, clinical practice and small sample studies have shown that megestrol combined with chemotherapy can improve CINV. This randomized controlled trial aimed to evaluate the clinical efficacy and safety of megestrol acetate combined with a 5-Hydroxytryptamine (5-HT3) receptor antagonist and dexamethasone in patients with CINV.
METHODS
Patients with malignant tumors who were treated with cisplatin-containing chemotherapy in our hospital from September 2018 to December 2019 were enrolled. A total of 120 patients were selected and randomly assigned to receive either megestrol acetate dispersible tablets with a 5-HT3 receptor antagonist and dexamethasone (megestrol group) or a 5-HT3 receptor antagonist plus dexamethasone (control group). Megestrol acetate dispersible tablets: 160 mg orally every morning from the day of chemotherapy until it lasts for ten days. Abstract IV of the quality-of-life scale for cancer patients in China was used to assess the quality of life (QOL) of the participants. All adverse reactions during chemotherapy were assessed according to the CTCAE 4.03 evaluation standard issued by the National Cancer Institute and divided into five grades according to severity.
RESULTS
For the control of nausea, the rates of complete prevention were significantly higher in the megestrol group than in the control patients during the delayed [53.3% (31/60) 30.0% (18/60), P=0.012] and overall [40.0% (24/60) 15.0% (9/60), P=0.002] observation periods. Moreover, the megestrol combination treatment group also achieved markedly higher rates of complete remission of vomiting than the control group during the delayed observation period [76.7% (46/60) 51.7% (31/60), P=0.001], achieving an overall higher proportion of remission during the study period [68.3% (41/60) 46.6% (28/60), P=0.0016].
CONCLUSIONS
The triple antiemetic protocol using megestrol acetate with a 5-HT3 receptor antagonist plus dexamethasone can improve CINV symptoms caused by highly emetogenic chemotherapy (HEC) with cisplatin, with an excellent control effect and few adverse reactions, especially for delayed CINV.
TRIAL REGISTRATION
Chinese Clinical Trial Registry ChiCTR1800017953.
PubMed: 36388808
DOI: 10.21037/atm-22-4809