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Polskie Archiwum Medycyny Wewnetrznej Nov 2008Anorexia-cachexia syndrome (ACS) often occurs in patients with advanced cancer. (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Anorexia-cachexia syndrome (ACS) often occurs in patients with advanced cancer.
OBJECTIVES
To review the effect of megestrol acetate (MA) in patients with ACS.
PATIENTS AND METHODS
To identify eligible studies, systematic review by Lopez et al. (2004) was used, electronic databases (MEDLINE, EMBASE and CENTRAL) were searched and reference lists of included studies were reviewed. The studies were included in the review if they were randomized, enrolled patients with non-hormone-sensitive cancer and ACS and assessed the effects of MA compared with placebo, other drugs or different doses of MA.
RESULTS
The study population is characterized by high mortality and progressive weight loss irrespective of the treatment. Compared to placebo, the effect of MA on survival is similar, but MA increases appetite (number needed to treat [NNT]: 3) and leads to weight gain (NNT: 8) in more patients. The data on other aspects of the quality of life are limited. The comparison of MA and glucocorticosteroids showed no statistical difference in their effect on appetite and weight.
CONCLUSIONS
Compared to placebo, MA reduces the symptoms of ACS, with no effect on survival. The beneficial effect of MA on the overall quality of life has not been confirmed. In identified studies the effect of MA and glucocorticosteroids on anorexia and cachexia is similar. The estimation of the treatment utility in ACS depends on the weight attributed to discomfort caused by symptoms, adverse effects of the drugs and the treatment cost. Because of the low quality of the included studies a new randomized controlled trial is needed for valid assessment of the effects of MA.
Topics: Anorexia; Appetite; Appetite Stimulants; Body Weight; Cachexia; Dose-Response Relationship, Drug; Humans; Megestrol Acetate; Neoplasms; Randomized Controlled Trials as Topic; Syndrome; Treatment Outcome
PubMed: 19140567
DOI: No ID Found -
Journal of Hazardous Materials Apr 2023The consumption of cytostatics, pharmaceuticals prescribed in chemotherapy, is increasing every year and worldwide, along with the incidence of cancer. The presence and...
The consumption of cytostatics, pharmaceuticals prescribed in chemotherapy, is increasing every year and worldwide, along with the incidence of cancer. The presence and the temporal evolution of cytostatics in wastewaters from a Portuguese hospital center was evaluated through a 9-month sampling campaign, comprising a total of one hundred and twenty-nine samples, collected from May 2019 to February 2020. Eleven cytostatics out of thirteen pharmaceuticals were studied, including flutamide, mycophenolate mofetil and mycophenolic acid, which have never been monitored before. Target analytes were extracted and quantified by solid-phase extraction coupled to liquid-chromatography-tandem mass spectrometry analysis; the method was fully validated. All pharmaceuticals were detected in at least one sample, bicalutamide being the one found with higher frequency (detected in all samples), followed by mycophenolic acid, which was also the compound detected at higher concentrations (up to 5340 ± 211 ng/L). Etoposide, classified as carcinogenic to humans, was detected in 60% of the samples at concentrations up to 142 ± 15 ng/L. The risk from exposure to cytostatics was estimated for aquatic organisms living in receiving bodies. Cyclophosphamide, doxorubicin, etoposide, flutamide, megestrol and mycophenolic acid are suspected to induce risk. Long-term and synergic effects should not be neglected, even for the cytostatics for which no risk was estimated.
Topics: Humans; Cytostatic Agents; Flutamide; Etoposide; Mycophenolic Acid; Water Pollutants, Chemical; Solid Phase Extraction; Environmental Monitoring; Pharmaceutical Preparations
PubMed: 36731320
DOI: 10.1016/j.jhazmat.2023.130883 -
Innovations in Clinical Neuroscience Jul 2014Acute marijuana use is classically associated with snacking behavior (colloquially referred to as "the munchies"). In support of these acute appetite-enhancing effects,...
Acute marijuana use is classically associated with snacking behavior (colloquially referred to as "the munchies"). In support of these acute appetite-enhancing effects, several authorities report that marijuana may increase body mass index in patients suffering from human immunodeficiency virus and cancer. However, for these medical conditions, while appetite may be stimulated, some studies indicate that weight gain is not always clinically meaningful. In addition, in a study of cancer patients in which weight gain did occur, it was less than the comparator drug (megestrol). However, data generally suggest that acute marijuana use stimulates appetite, and that marijuana use may stimulate appetite in low-weight individuals. As for large epidemiological studies in the general population, findings consistently indicate that users of marijuana tend to have lower body mass indices than nonusers. While paradoxical and somewhat perplexing, these findings may be explained by various study confounds, such as potential differences between acute versus chronic marijuana use; the tendency for marijuana use to be associated with other types of drug use; and/or the possible competition between food and drugs for the same reward sites in the brain. Likewise, perhaps the effects of marijuana are a function of initial weight status-i.e., maybe marijuana is a metabolic regulatory substance that increases body weight in low-weight individuals but not in normal-weight or overweight individuals. Only further research will clarify the complex relationships between marijuana and body weight.
PubMed: 25337447
DOI: No ID Found -
Clinical and Experimental Reproductive... Dec 2020Endometrial cancer (EC) in young women tends to be early-stage and low-grade; therefore, such cases have good prognoses. Fertility-sparing treatment with progestin is a...
Endometrial cancer (EC) in young women tends to be early-stage and low-grade; therefore, such cases have good prognoses. Fertility-sparing treatment with progestin is a potential alternative to definitive treatment (i.e., total hysterectomy, bilateral salpingo-oophorectomy, pelvic washing, and/or lymphadenectomy) for selected patients. However, no evidence-based consensus or guidelines yet exist, and this topic is subject to much debate. Generally, the ideal candidates for fertility-sparing treatment have been suggested to be young women with grade 1 endometrioid adenocarcinoma confined to the endometrium. Magnetic resonance imaging should be performed to rule out myometrial invasion and extrauterine disease before initiating fertility-sparing treatment. Although various fertility-sparing treatment methods exist, including the levonorgestrel-intrauterine system, metformin, gonadotropin-releasing hormone agonists, photodynamic therapy, and hysteroscopic resection, the most common method is high-dose oral progestin (medroxyprogesterone acetate at 500-600 mg daily or megestrol acetate at 160 mg daily). During treatment, re-evaluation of the endometrium with dilation and curettage at 3 months is recommended. Although no consensus exists regarding the ideal duration of maintenance treatment after achieving regression, it is reasonable to consider maintaining the progestin therapy until pregnancy with individualization. According to the literature, the ovarian stimulation drugs used for fertility treatments appear safe. Hysterectomy should be performed after childbearing, and hysterectomy without oophorectomy can also be considered for young women. The available evidence suggests that fertility-sparing treatment is effective and does not appear to worsen the prognosis. If an eligible patient strongly desires fertility despite the risk of recurrence, the clinician should consider fertility-sparing treatment with close follow-up.
PubMed: 33181010
DOI: 10.5653/cerm.2020.03629 -
Translational Cancer Research Dec 2020Over the last twenty years, the incidence of early endometrial cancer (EC) and atypical endometrial hyperplasia (AEH) among women of reproductive age is increasing... (Review)
Review
Over the last twenty years, the incidence of early endometrial cancer (EC) and atypical endometrial hyperplasia (AEH) among women of reproductive age is increasing rapidly, likely due to a combination of factors including increased prevalence of obesity and delayed of childbirths. Regarding preoperative diagnosis of endometrial neoplasia, it is still debated which is the most accurate and reliable method to obtain endometrial histopathological samples with fractional dilatation and curettage (D&C) having been considered, for a long time, as the method of choice. Nowadays, the advent of in-office endometrial biopsy with or without hysteroscopy has radically changed the approach, giving the opportunity to perform the endometrial biopsy under direct visualization. However, the lack of agreement about its diagnostic accuracy is still relevant. Since a significant number of women with AEH and/or EC are of childbearing age, a fertility-sparing diagnostic and therapeutic approach should be considered in all cases. The feasibility, safety and efficacy of fertility-sparing strategies involving hysteroscopic focal resections in conjunction with hormonal therapies have been evaluated and beneficial effects have been confirmed in several studies and one meta-analysis. Both local and systemic administration of hormonal therapies are currently used. Oral progestin, including medroxyprogesterone acetate (MPA) and megestrol acetate, are the most commonly used therapies. Nowadays, new therapeutic approaches, such as levonorgestrel intrauterine systems (LNG-IUS), gonadotropin-releasing hormone (GnRH) agonists, combined megestrol acetate and metformin, and other combinations of therapies are also used as first line therapies or after the hysteroscopic resection of the lesion. However, it is still unclear which approach provides higher clinical response with lower relapse rate, in addition to preserving fertility in women desiring to conceive. The aim of this narrative review is to summarize the available evidence regarding the evaluation and management with fertility-sparing treatments options of women with AEC and EC.
PubMed: 35117379
DOI: 10.21037/tcr-20-2092 -
Journal de Gynecologie, Obstetrique Et... Feb 2005As the biological effects of progestins vary according to their molecular structure, it becomes essential to differentiate the various types of progestins, particularly... (Review)
Review
UNLABELLED
As the biological effects of progestins vary according to their molecular structure, it becomes essential to differentiate the various types of progestins, particularly with regard to the breast.
OBJECTIVE
The purpose of this review was to gather published data on the effects of a 19-norprogesterone derivative, nomegestrol acetate, on the breast. Materials and methods. All experimental and clinical published studies reporting data in the literature on nomegestrol acetate and breast were reviewed.
RESULTS
In experiments on steroid receptors, it was shown that nomegestrol acetate presents a high binding specificity and affinity for progesterone receptors, notably in normal and cancerous human breast tissues. It sharply inhibits synthesis of progesterone receptors in hormone-dependent T-47D human breast cancer cells grown in an estrogenic culture medium, thereby demonstrating its strong progestational activity. On the other hand, it does not bind to estrogen receptors and lacks any estrogenic potential, confirmed by the lack of induction of alkaline phosphatase activity of endometrial Ishikawa cells. Estrogen-induced synthesis of estrogen receptors is also inhibited by nomegestrol acetate, a major determinant of its strong intrinsic anti-estrogenic activity. Unlike androgenic progestins (e.g. 19-nortestosterone derivatives and medroxyprogesterone acetate) which may act indirectly on the breast by inducing modifications of sex hormone binding globulin (SHBG) and insulin-like growth factor-I (IGF-I), nomegestrol acetate is devoid of any androgenic activity. In studies carried out on the effects of progestins on enzyme activities involved in estradiol (E2) formation in breast tissue, nomegestrol acetate can control E2 levels in breast cancer tissue in vitro: it inhibits estrone sulfatase activity that converts estrone sulfate (E1S) to estrone (E1) and inhibits 17beta-hydroxysteroid dehydrogenase type 1 activity that converts E1 to E2, resulting in blockade of E2 bioformation in MCF-7 and T-47D human breast cancer cells. It also stimulates sulfotransferase activity and subsequently the transformation of non conjugated estrogens E1 and E2 into biologically inactive estrogen sulfates. In vitro studies on cell proliferation have demonstrated that nomegestrol acetate, on the one hand, is unable to stimulate proliferation of MCF-7 cells cultured in a medium devoid of estrogens and, on the other hand, can exert antiproliferative effects on T-47D cells grown in an estrogenic environment. Furthermore, studies on mammary apoptosis have shown that the withdrawal of nomegestrol acetate induces apoptosis peak of normal human breast epithelial cells in vitro and in vivo. In clinical trials carried out with premenopausal women, nomegestrol acetate administered in antigonadotropic sequence has demonstrated its efficacy in the treatment of cyclical mastodynia and early onset benign breast diseases. With postmenopausal hormone replacement therapy (HRT) combining estrogen and nomegestrol acetate, clinical trial results showed low incidence of mastodynia while under treatment as well as moderate increase in mammographic density, particularly with continuous combined regimens, however rapidly reversed by a short-term suspension of HRT. Noclinical data with this progestagen is available on breast cancer risk.
CONCLUSION
In addition to efficacy on mastodynia, in vitro and in vivo study results support the good tolerance of nomegestrol acetate on breast, in the short and medium term.
Topics: Apoptosis; Breast Diseases; Cell Division; Cells, Cultured; Female; Humans; Mammary Glands, Human; Megestrol; Norpregnadienes; Radiography; Receptors, Estrogen; Receptors, Steroid
PubMed: 15767920
DOI: 10.1016/s0368-2315(05)82673-0 -
Chronic Obstructive Pulmonary Diseases... Nov 2015Underweight chronic obstructive pulmonary disease (COPD) patients with involuntary weight loss have a poor prognosis; no effective therapy is currently available. We...
Underweight chronic obstructive pulmonary disease (COPD) patients with involuntary weight loss have a poor prognosis; no effective therapy is currently available. We conducted the first clinical trial seeking to determine whether combination therapy with an appetite stimulant and an anabolic steroid would have beneficial effects on body composition for patients with COPD cachexia. We conducted a 12-week pilot study in which 4 men and 5 women (age 64±10 y, forced expiratory volume in 1 second [FEV] 31±9 %pred., body mass index [BMI] 18±3 kg/m) with low-normal testosterone levels (average 532±45ng/dl in men and 12.4±5.3ng/dl in women) and weight loss ≥10 lbs over the previous year were treated with oral megestrol acetate 800mg/day plus weekly testosterone enanthate injections, initially 125 mg in men and 40 mg in women, with doses subsequently adjusted targeting circulating nadir testosterone levels of 850 and 300 ng/dl, respectively. On treatment, nadir testosterone level increases averaged 160±250 ng/dl (NS) in men and 322±49 (<0.001) ng/dl in women. Body weight increased in all individuals, with average end-intervention weight gain of 3.1±2.2 kg (<0.005). Two women and 2 men had COPD exacerbations and did not complete the 12-week study. In the 5 individuals who completed, dual energy x ray absorptiometry (DEXA) scans revealed an average 2.0±1.5 kg lean mass and 2.3±1.7 kg fat mass increase (each <0.05). No adverse effects of treatment were detected. Combination therapy reversed the trajectory of involuntary weight loss and increased lean mass in cachectic COPD patients. Though the interventions were apparently well tolerated, participant drop-out rate was high. Larger randomized placebo-controlled long-term studies with functional outcomes are needed.
PubMed: 28848861
DOI: 10.15326/jcopdf.3.1.2015.0128 -
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 -
Cancer Control : Journal of the Moffitt... 2002Anti-aromatase agents now have a central role in the management of breast cancer in postmenopausal women; they are superior to megestrol acetate as second-line therapy... (Review)
Review
Anti-aromatase agents now have a central role in the management of breast cancer in postmenopausal women; they are superior to megestrol acetate as second-line therapy and to tamoxifen for initial therapy of metastatic disease. They also are highly active as neoadjuvant therapy. Two classes of anti-aromatase agents are available: steroidal (eg, exemestane) and nonsteroidal (eg, anastrozole, letrozole). Although both types of agents act on the aromatase enzyme, they do so by different mechanisms and have different effects on cellular aromatase activity. Nonsteroidal agents are associated with increased aromatase enzyme content and steroidal agents are associated with decreased content. The increase in aromatase content seen with the nonsteroidal agents may in part explain the development of resistance with these agents and the ability of the steroidal agent exemestane to induce a response when nonsteroidal agents fail. Because the anti-aromatase agents almost completely eliminate endogenous estrogen production, they not only affect breast cancer tissues, but also may alter the function of other estrogen-responsive tissues. However, preclinical data show that the steroidal agent exemestane may actually improve bone and lipid metabolism. In addition, no increase in clinical fracture rate has been noted in women treated with exemestane in metastatic trials; the fracture risk has not yet been studied following prolonged exposure in healthy women. Exemestane associated beneficial effects on these end organs may be due to the steroidal nature of both the parent compound and its principal metabolite, 17-hydroexemestane. Similar benefits have not been reported with nonsteroidal antiaromatase agents. Based on their excellent activity in the metastatic setting, anti-aromatase agents are now being evaluated in the adjuvant setting and in pilot studies for chemoprevention. These studies will provide long-term data in healthy women and will help to differentiate anti-aromatase agents, in terms of their efficacy in the treatment of breast cancer and their effects on end organs.
Topics: Anastrozole; Androstadienes; Antineoplastic Agents, Hormonal; Aromatase Inhibitors; Breast Neoplasms; Clinical Trials as Topic; Enzyme Inhibitors; Female; Humans; Letrozole; Neoadjuvant Therapy; Nitriles; Postmenopause; Research Design; Triazoles
PubMed: 11965225
DOI: 10.1177/107327480200902S01 -
Cancer Control : Journal of the Moffitt... Apr 2016A man aged 65 years with metastatic renal cell carcinoma presented for evaluation after a recent fall. A thorough workup of the case was performed and secondary adrenal...
A man aged 65 years with metastatic renal cell carcinoma presented for evaluation after a recent fall. A thorough workup of the case was performed and secondary adrenal insufficiency induced by the administration of megestrol acetate was determined to be the cause. Adrenal insufficiency is a serious disorder that is a potential adverse event of megestrol acetate, a medication used to help patients with cancer cachexia increase their appetite and gain weight. This association is not well recognized in clinical practice, so this case highlights the importance of distinguishing possible endocrine complications induced by the long-term administration or sudden discontinuation of megestrol acetate.
Topics: Adrenal Insufficiency; Aged; Humans; Male; Megestrol Acetate
PubMed: 27218795
DOI: 10.1177/107327481602300212