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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 -
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 -
Gynecologic Oncology Research and... 2017Endometrial cancer is the most common gynecologic malignancy in the United States, accounting for 6% of cancers in women. In 2017, an estimated 61,380 women were... (Review)
Review
Endometrial cancer is the most common gynecologic malignancy in the United States, accounting for 6% of cancers in women. In 2017, an estimated 61,380 women were diagnosed with endometrial cancer, and approximately 11,000 died from this disease. From 1987 to 2008, there was a 50% increase in the incidence of endometrial cancer, with an approximate 300% increase in the number of associated deaths. Although there are many chemotherapeutic and targeted therapy agents approved for ovarian, fallopian tube and primary peritoneal cancers, since the 1971 approval of megestrol acetate for the palliative treatment of advanced endometrial cancer, only pembrolizumab has been Food and Drug Administration (FDA)-approved for high microsatellite instability (MSI-H) or mismatch repair deficient (dMMR) endometrial cancer; this highlights the need for new therapies to treat advanced, recurrent, metastatic endometrial cancer. In this review, we discuss current and emerging treatment options for endometrial cancer, including chemotherapy, targeted therapy, and immunotherapy. The National Cancer Institute (NCI) and others are now focusing their efforts on the design of scientifically rational targeted therapy and immunotherapy trials for specific molecular phenotypes of endometrial cancer. This is essential for the advancement of cancer care for women, which is threatened by a severe enrollment decline of approximately 80% for gynecologic oncology clinical trials.
PubMed: 29214032
DOI: 10.1186/s40661-017-0056-7 -
International Journal of Women's Health 2014Endometrial cancer (EC) is the most common gynecologic malignancy in developed countries and affects predominantly postmenopausal women. It is estimated, however, that... (Review)
Review
Endometrial cancer (EC) is the most common gynecologic malignancy in developed countries and affects predominantly postmenopausal women. It is estimated, however, that 15%-25% of women will be diagnosed before menopause. As more women choose to defer childbearing until later in life, the feasibility and safety of fertility-sparing EC management have been increasingly studied. Definitive treatment of total hysterectomy and bilateral salpingo-oophorectomy precludes future fertility and may thus be undesirable by women who wish to maintain their reproductive potential. However, the consideration of conservative management carries the oncologic risks of unstaged EC and the risk of missing a synchronous ovarian cancer. It is further complicated by the lack of consensus regarding the initial assessment, treatment, and surveillance. Conservative treatment with progestins has been shown to be a feasible and safe fertility-sparing approach for women with low grade, early stage EC with no myometrial invasion. The two most commonly adopted regimens are medroxyprogesterone acetate at 500-600 mg daily and megestrol acetate at 160 mg daily for a minimum of 6-9 months, with initial response rates commonly reported between 60% and 80% and recurrence rates between 25% and 40%. Photodynamic therapy and hysteroscopic EC excision have recently been reported as alternative approaches to progestin therapy alone. However, limited efficacy and safety data exist. Live birth rates after progestin therapy have typically been reported around 30%; however, when focusing only on those who do pursue fertility after successful treatment, the live birth rates were found to be higher than 60%. Assisted reproductive technology has been associated with a higher live birth rate compared with spontaneous conception, most likely reflecting the presence of infertility at baseline. Close follow-up is of paramount importance, and definitive treatment after completion of childbearing is advised.
PubMed: 25114594
DOI: 10.2147/IJWH.S47232 -
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 -
Acta Crystallographica. Section E,... Apr 2012The title compound, C(24)H(34)O(4), is a precursor of Megestrol acetate. Ring A has a half-chair conformation [Q = 0.446 (3) Å, θ = 54.6 (4)° and ϕ =...
The title compound, C(24)H(34)O(4), is a precursor of Megestrol acetate. Ring A has a half-chair conformation [Q = 0.446 (3) Å, θ = 54.6 (4)° and ϕ = 9.5 (4)°]. Ring D adopts a 13β-envelope conformation [Q = 0.463 (2) Å and ϕ = 188.2 (3)°].
PubMed: 22590046
DOI: 10.1107/S1600536812008665 -
The Journal of Nutrition, Health & Aging Feb 2012The objective of this review was to investigate the range of pharmacological interventions that have been studied for treatment of geriatric cachexia, and to evaluate... (Review)
Review
OBJECTIVE
The objective of this review was to investigate the range of pharmacological interventions that have been studied for treatment of geriatric cachexia, and to evaluate their effect on selected clinical outcomes in this population.
METHODS
Databases including Medline and Cochrane Central Register of Controlled Trials were searched up to March 2010 with search terms including "cache*", "intervention", "megestrol acetate" and "cytokine inhibitors". Studies investigating subjects with mean age <60y or disease-related cachexia were excluded. Outcomes assessed were weight or BMI, body composition, appetite and laboratory parameters indicative of cachexia.
RESULTS
Fifteen publications met the selection criteria, reporting on ten studies. Seven studies investigated use of megestrol acetate (MA): two randomised controlled trials, one case control study, two pre-test/post-test studies and two retrospective chart reviews. Weight/BMI was common amongst outcomes and these studies showed an improvement in weight compared with baseline. MA studies which investigated body composition, appetite and/or laboratory parameters provided some evidence for improvement in these outcomes. Three randomised controlled trials investigated the use of other interventions: ghrelin, growth hormone and vitamin supplementations. All demonstrated a significant increase in lean body mass. The only other outcome of interest in these three trials was weight in one study with a significant increase demonstrated.
CONCLUSION
Little investigation has been conducted in this population and the diagnosis of cachexia is problematic however these trials provide preliminary evidence for beneficial outcomes in older adults likely to have cachexia. Further high quality adequately powered prospective studies are necessary to provide effective treatment for geriatric cachexia.
Topics: Aged; Aged, 80 and over; Aging; Appetite; Appetite Stimulants; Body Composition; Body Mass Index; Body Weight; Cachexia; Cytokines; Female; Humans; Male; Megestrol Acetate; Nutritional Physiological Phenomena; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 22323350
DOI: 10.1007/s12603-011-0083-8 -
The Cochrane Database of Systematic... Oct 2009Endocrine therapy removes the influence of oestrogen on breast cancer cells and so hormonal treatments such as tamoxifen, megestrol acetate and medroxyprogesterone... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Endocrine therapy removes the influence of oestrogen on breast cancer cells and so hormonal treatments such as tamoxifen, megestrol acetate and medroxyprogesterone acetate have been in use for many years for advanced breast cancer. Aromatase inhibitors (AIs) inhibit oestrogen synthesis in the peripheral tissues and have a similar tumour-regressing effect to other endocrine treatments. Aminoglutethimide was the first AI in clinical use and now the third generation AIs, anastrozole, exemestane and letrozole, are in current use. Randomised trial evidence on response rates and side effects of these drugs is still limited.
OBJECTIVES
To compare AIs to other endocrine therapy in the treatment of advanced breast cancer in postmenopausal women.
SEARCH STRATEGY
For this update, the Cochrane Breast Cancer Group Specialised Register and the Cochrane Central Register of Controlled Trials (CENTRAL) and relevant conference proceedings were searched (to 30 June 2008).
SELECTION CRITERIA
Randomised controlled trials in postmenopausal women comparing the effects of any AI versus other endocrine therapy, no endocrine therapy, or a different AI in the treatment of advanced (metastatic) breast cancer. Non-English language publications, comparisons of the same AI at different doses, AIs used as neoadjuvant treatment, or outcomes not related to tumour response were excluded.
DATA COLLECTION AND ANALYSIS
Data from published trials were extracted independently by two review authors and cross-checked by a third. Hazard ratios (HR) were derived for analysis of time-to-event outcomes (overall and progression-free survival). Odds ratios (OR) were derived for objective response, clinical benefit, and toxicity.
MAIN RESULTS
Thirty-seven trials were identified, 31 of which were included in the main analysis of any AI versus any other treatment (11,403 women). No trials were excluded due to inadequate allocation concealment. The pooled estimate showed a significant survival benefit for treatment with an AI over other endocrine therapies (HR 0.90, 95% CI 0.84 to 0.97). A subgroup analysis of the three commonly prescribed AIs (anastrozole, exemestane, letrozole) also showed a similar survival benefit (HR 0.88, 95% CI 0.80 to 0.96). There were very limited data to compare one AI with a different AI, but these suggested an advantage for letrozole over anastrozole.AIs have a different toxicity profile to other endocrine therapies. For those currently prescribed, and for all AIs combined, they had similar levels of hot flushes and arthralgia; increased risks of rash, nausea, diarrhoea and vomiting; but a 71% decreased risk of vaginal bleeding and 47% decrease in thromboembolic events compared with other endocrine therapies.
AUTHORS' CONCLUSIONS
In women with advanced (metastatic) breast cancer, aromatase inhibitors including those in current clinical use show a survival benefit when compared to other endocrine therapy.
Topics: Antineoplastic Agents, Hormonal; Aromatase Inhibitors; Breast Neoplasms; Female; Humans; Neoplasms, Hormone-Dependent; Postmenopause; Randomized Controlled Trials as Topic
PubMed: 19821307
DOI: 10.1002/14651858.CD003370.pub3 -
BioMed Research International 2013Primary liver cancer is the fifth most common cancer worldwide and the third most common cause of cancer mortality. Hepatocellular carcinoma (HCC) accounts for 85% to... (Review)
Review
Primary liver cancer is the fifth most common cancer worldwide and the third most common cause of cancer mortality. Hepatocellular carcinoma (HCC) accounts for 85% to 90% of primary liver cancers. Major risk factors for HCC include infection with HBV or HCV, alcoholic liver disease, and most probably nonalcoholic fatty liver disease. In general, men are two to four times more often associated with HCC than women. It can be suggested that sex hormones including progesterone may play some roles in HCC. Rather, very limited information discusses its potential involvement in HCC. This paper thus collects some recent studies of the potential involvement of progesterone and related compounds in HCC from basic and clinical aspects. In addition, two synthetic progestins, megestrol acetate (MA) and medroxyprogesterone acetate (MPA), will be discussed thoroughly. It is noted that progesterone can also serve as the precursor for androgens and estrogens produced by the gonadal and adrenal cortical tissues, while men have a higher incidence of HCC than women might be due to the stimulatory effects of androgen and the protective effects of estrogen. Eventually, this paper suggests a new insight on the associations of progesterone and related compounds with HCC development and treatment.
Topics: Androgens; Antineoplastic Agents, Hormonal; Carcinoma, Hepatocellular; Estrogens; Female; Humans; Liver Neoplasms; Male; Medroxyprogesterone Acetate; Megestrol Acetate; Sex Characteristics
PubMed: 23484104
DOI: 10.1155/2013/290575 -
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