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megestrol

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Description

Megestrol acetate is a synthetic progestin that is used primarily to treat cancer-related anorexia-cachexia syndrome (CACS) and to suppress the growth of certain types of tumors. It is also used off-label for a variety of other conditions, such as endometriosis, uterine fibroids, and breast cancer. Megestrol acetate works by binding to progesterone receptors in the body. This binding stimulates the appetite and promotes weight gain, which can be helpful for patients with CACS. Megestrol acetate can also slow the growth of certain tumors, such as breast cancer, by blocking the effects of estrogen. Megestrol acetate is typically taken by mouth in tablet form. It is important to note that megestrol acetate can have significant side effects, including blood clots, stroke, and heart attack. It is also important to note that megestrol acetate can interact with other medications, so it is important to talk to your doctor before taking it.'

Megestrol: A progestational hormone used most commonly as the acetate ester. As the acetate, it is more potent than progesterone both as a progestagen and as an ovulation inhibitor. It has also been used in the palliative treatment of breast cancer. [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

megestrol : A 3-oxo Delta(4)-steroid that is pregna-4,6-diene-3,20-dione substituted by a methyl group at position 6 and a hydroxy group at position 17. [Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Cross-References

ID SourceID
PubMed CID19090
CHEMBL ID4071215
CHEBI ID6722
SCHEMBL ID8942
MeSH IDM0013296

Synonyms (44)

Synonym
megestrolum [inn-latin]
einecs 222-628-6
17-hydroxy-6-methylpregna-4,6-diene-3,20-dione
pregna-4,6-diene-3,20-dione, 17-hydroxy-6-methyl-
hsdb 3233
megestrol [inn:ban]
megestrolum
CHEBI:6722 ,
megestrolo
megestrol
3562-63-8
C07120
17-hydroxy-6-methylpregna-3,6-diene-3,20-dione
chronopil
(8r,9s,10r,13s,14s,17r)-17-acetyl-17-hydroxy-6,10,13-trimethyl-2,8,9,11,12,14,15,16-octahydro-1h-cyclopenta[a]phenanthren-3-one
megestrol (inn)
chronopil (tn)
D08167
unii-ea6ld1m70m
ea6ld1m70m ,
megestrol [vandf]
megestrol [hsdb]
megestrol [inn]
megestrol acetate impurity b [ep impurity]
megestrol [who-dd]
S5738
SCHEMBL8942
AC-32473
gtpl9128
4,6-pregnadien-6-methyl-17-ol-3,20-dione
CS-0013903
HY-B1834
Q410513
(8r,9s,10r,13s,14s,17r)-17-acetyl-17-hydroxy-6,10,13-trimethyl-8,9,10,11,12,13,14,15,16,17-decahydro-1h-cyclopenta[a]phenanthren-3(2h)-one
CHEMBL4071215
pregna-4,6-diene-3,20-dione, 17-hydroxy-6-methyl-; 17-hydroxy-6-methylpregna-4,6-diene-3,20-dione; megestrol; 6-methyl-17-hydroxypregna-4,6-diene-3,20-dione
MS-25250
DTXSID001009330 ,
compound 5071
dtxcid001436159
g03db02
g03ac05
megestrolum (inn-latin)
l02ab01

Research Excerpts

Overview

Nomegestrol acetate is a potent, orally active progestogen. It is a strong anti-sulfatase agent, in particular with cancerous breast tissues. It has favourable tolerability profile and neutral metabolic characteristics.

ExcerptReferenceRelevance
"Megestrol acetate is a common and efficient anticancer progesterone. "( Megestrol acetate drives endometrial carcinoma cell senescence via interacting with progesterone receptor B/FOXO1 axis.
Shi, H; Wang, H, 2021
)
3.51
"Nomegestrol acetate is a potent, orally active progestogen with a favourable tolerability profile and neutral metabolic characteristics."( Nomegestrol acetate: pharmacology, safety profile and therapeutic efficacy.
Lello, S, 2010
)
1.64
"Nomegestrol acetate is a selective progestogen and a potent inhibitor of ovulation in the rat and monkey."( Nomegestrol acetate: steroid receptor transactivation profile in Chinese hamster ovary cells and ovulation inhibition in rat and monkey.
Kuil, CW; Lam, TW; van Diepen, HA, 2011
)
1.81
"Nomegestrol acetate is a strong anti-sulfatase agent, in particular with cancerous breast tissues."( Control of sulfatase activity by nomegestrol acetate in normal and cancerous human breast tissues.
Chetrite, GS; Cortes-Prieto, J; Pasqualini, JR; Philippe, JC; Shields-Botella, J; Thomas, JL,
)
0.97
"Megestrol acetate is an effective treatment for some patients with AIDS-related anorexia and cachexia."( Randomized trials of megestrol acetate for AIDS-associated anorexia and cachexia.
Von Roenn, JH, 1994
)
1.33
"Nomegestrol acetate is an innovative and efficient molecule in the treatment of menstrual disorders. "( [Use of nomegestrol acetate in the treatment of menstruation disorders. Our experience in 56 cases].
Lombardi, PA; Lombardi, PL; Persiani, P; Radici, E, 1997
)
1.42
"Megestrol acetate is an effective, well-tolerated agent in previously untreated patients with advanced breast cancer."( Front-line hormonal therapy for patients with advanced breast cancer: a community oncology research program.
Anderson, S; Sigal, RB; Smalley, RV, 1990
)
1
"Nomegestrol acetate is a potent progestogen and further studies are required to determine its lowest effective dose."( The effects of the addition of nomegestrol acetate to post-menopausal oestrogen therapy.
Fraser, DI; Padwick, ML; Pryse-Davies, J; Ryder, TA; White, J; Whitehead, MI, 1989
)
1.12

Effects

Nomegestrol acetate has a stimulatory effect on sulfotransferase activity. At low doses (5 x 10(-8) and 5 x 10 (-7) mol/l) this compound strongly increases the activity of this enzyme by 60.6% and 83%.

Nomegestrol acetate has been used successfully for the treatment of some gynaecological disorders (menstrual disturbances, dysmenorrhoea) and as a component of HRT in combination with estradiol for the relief of menopausal symptoms. It has proven its neutral effects on lipid metabolism and does not alter the beneficial estrogen-induced lipid effects.

ExcerptReferenceRelevance
"Nomegestrol acetate has a stimulatory effect on sulfotransferase activity: at low doses (5 x 10(-8) and 5 x 10(-7) mol/l) this compound strongly increases the activity of this enzyme by 60.6% and 83%, respectively, in the MCF-7 cells and by 69.2% at 5 x 10(-7) mol/l in T-47D cells."( Effect of nomegestrol acetate on human estrogen sulfotransferase activity in the hormone-dependent MCF-7 and T-47D breast cancer cell lines.
Chetrite, GS; Paris, J; Pasqualini, JR; Philippe, JC; Shields-Botella, J,
)
1.07
"Megestrol acetate has a role in the palliation of patients with progressive disease despite initial hormonal therapy."( Megestrol acetate in the treatment of metastatic carcinoma of the prostate.
Venner, P, 1992
)
2.45
"Nomegestrol acetate has been used successfully for the treatment of some gynaecological disorders (menstrual disturbances, dysmenorrhoea, premenstrual syndrome) and as a component of HRT in combination with estradiol for the relief of menopausal symptoms; it has been approved in Europe as monotherapy for the treatment of the menopausal syndrome, uterine diseases and menorrhagia, and in combination with an estrogen for the treatment of menopausal symptoms."( Nomegestrol acetate: pharmacology, safety profile and therapeutic efficacy.
Lello, S, 2010
)
1.64
"Nomegestrol acetate has proven its neutral effects on lipid metabolism and does not alter the beneficial estrogen-induced lipid effects."( [Effects of a 19-norprogesterone derivative, the fourth decade nomegestrol acetate, on lipids].
Colau, JC; Jamin, C; Pélissier, C, 2003
)
1.11
"Nomegestrol acetate has a stimulatory effect on sulfotransferase activity: at low doses (5 x 10(-8) and 5 x 10(-7) mol/l) this compound strongly increases the activity of this enzyme by 60.6% and 83%, respectively, in the MCF-7 cells and by 69.2% at 5 x 10(-7) mol/l in T-47D cells."( Effect of nomegestrol acetate on human estrogen sulfotransferase activity in the hormone-dependent MCF-7 and T-47D breast cancer cell lines.
Chetrite, GS; Paris, J; Pasqualini, JR; Philippe, JC; Shields-Botella, J,
)
1.07
"Megestrol acetate has been found to increase appetite, food intake, and weight in randomized, placebo-controlled trials in patients with advanced malignancies and in patients with AIDS."( Treatment of anorexia with megestrol acetate.
Tchekmedyian, NS, 1993
)
1.3
"Megestrol acetate has been reported to increase appetite and body weight, and a linear dose-response relation for doses from 160 up to 1600 mg/day has been proposed."( Low dose megestrol acetate can abrogate cachexia in advanced tumor patients receiving systemic interferon-alpha and/or interleukin-2 based antineoplastic therapy.
Ackermann, M; Atzpodien, J; Kirchner, H, 1993
)
1.42
"Megestrol acetate has been reported to improve appetite and quality of life and to decrease nausea and vomiting in patients with cancer anorexia/cachexia. "( Randomized double-blind placebo-controlled trial of cisplatin and etoposide plus megestrol acetate/placebo in extensive-stage small-cell lung cancer: a North Central Cancer Treatment Group study.
Ghosh, C; Jett, JR; Jung, SH; Kugler, JW; Kuross, SA; Loprinzi, CL; Mailliard, JA; Maksymiuk, AW; Owen, D; Rowland, KM; Schaefer, PL; Shaw, EG; Tschetter, LK; Washburn, JH; Webb, TA, 1996
)
1.96
"Megestrol acetate has proved to be of positive impact upon synchronisation of oestrus in beef cows. "( [Use of megesterol acetate for synchronization of estrus in cows].
Darovskikh, VE; Klinskiĭ, IuD; Ravilov, M, 1977
)
1.7
"Megestrol acetate has been tested for its applicability to synchronisation of oestrus in 463 mature heifers in the framework of preclinical and clinical experiments. "( [Studies on the use of megestrol acetate for estrus synchronization in heifers].
Bach, S; Barth, T; Bruer, W; Busch, W; Klinsky, JD; Köhler, H; Lusky, K, 1977
)
2.01
"Megestrol acetate has a role in the palliation of patients with progressive disease despite initial hormonal therapy."( Megestrol acetate in the treatment of metastatic carcinoma of the prostate.
Venner, P, 1992
)
2.45
"Megestrol acetate has few side effects, and has the advantage of stimulating appetite and weight gain, a benefit in cancer patients."( Megestrol acetate: clinical experience.
Canetta, R; Kelley, S; Nicaise, C; Rozencweig, M; Schacter, L; Smaldone, L, 1989
)
2.34
"Megestrol acetate has been observed to produce weight gain in patients with hormone-sensitive tumors and has recently been noted to produce a similar degree of weight gain in those with hormone insensitive tumors."( Studies of high-dose megestrol acetate: potential applications in cachexia.
Aisner, J; Novak, M; Parnes, H; Tait, N; Tchekmedyian, NS, 1988
)
1.32
"Megestrol acetate has only limited efficacy in patients previously treated for prostatic cancer by hormonal manipulation."( Phase II study of megestrol acetate for metastatic carcinoma of the prostate.
Crombie, C; Dalley, D; Devine, R; Page, J; Raghavan, D; Rosen, M; Woods, R, 1987
)
1.33
"Megestrol acetate has been observed anecdotally to produce weight gain."( Appetite stimulation with megestrol acetate in cachectic cancer patients.
Aisner, J; Greco, FA; Moody, M; Tait, N; Tchekmedyian, NS, 1986
)
1.29

Treatment

Megestrol acetate treatment resulted in a decline in dry matter, protein, lactic acid, and acid phosphatase activity. Pretreatment with megestrol showed no significant effect on clinical ratings.

ExcerptReferenceRelevance
"Megestrol acetate-treated patients had a significantly greater mean maximum weight gain (p = 0.027) and appetite stimulation (p = 0.021) than did placebo-treated patients."( Randomized trials of megestrol acetate for AIDS-associated anorexia and cachexia.
Von Roenn, JH, 1994
)
1.33
"Megestrol-treated patients, in comparison with the placebo group, showed statistically significant increases in maximum flow rate at fourteen, sixteen, and twenty weeks after therapy, and statistically significant increases in mean flow rate over the placebo patients at ten, twelve, fourteen, and twenty weeks."( Effect of megestrol acetate on uroflow rates in patients with benign prostatic hypertrophy: double-blind study.
Albert, JD; Geller, J; Nelson, CG; Pratt, C, 1979
)
1.38
"Megestrol acetate treatment resulted in a decline in dry matter, protein, lactic acid, and acid phosphatase activity."( Studies on physiology & biochemistry of cervix: response of rat cervix to a continuous low dose of megestrol acetate.
Dasgupta, PR; Kar, AB; Karkun, JN; Mehrotra, PK; Sanwal, PC, 1970
)
1.09
"Pretreatment with megestrol showed no significant effect on clinical ratings."( Megestrol attenuates the hormonal response to CCK-4-induced panic attacks.
Gescher, DM; Goedeken, B; Jahn, H; Kellner, M; Raedler, TJ; Wiedemann, K, 2006
)
2.1
"Treatment with megestrol acetate caused a non-significant reduction in serum estradiol (mean reduction of 19%, 0.05 less than P less than 0.1) but significant reductions in serum estrone (mean reduction of 20%, P less than 0.02) and serum estrone sulfate (mean reduction of 54%, P less than 0.005) compared to treatment with medroxyprogesterone acetate."( Influence of progestins on serum hormone levels in postmenopausal women with advanced breast cancer--II. A differential effect of megestrol acetate and medroxyprogesterone acetate on serum estrone sulfate and sex hormone binding globulin.
Lundgren, S; Lønning, PE, 1990
)
0.82
"Treatment with megestrol acetate for 3 days caused the fertilized eggs to enter the uterus approximately 48 h prematurely."( Investigations into the mechanism of the antifertility action of minimal doses of megestrol acetate in the rabbit.
Kendle, KE; Telford, JM, 1970
)
0.81

Toxicity

ExcerptReferenceRelevance
" In the investigational group, the most frequently reported adverse events were acne (16."( Efficacy, safety, and tolerability of a monophasic oral contraceptive containing nomegestrol acetate and 17β-estradiol: a randomized controlled trial.
Bahamondes, L; Darney, P; Kaunitz, AM; Korver, T; Sommer, W; Verhoeven, C; Westhoff, C, 2012
)
0.6
" Secondary outcomes included documented improvement in appetite, change in weight and various laboratory parameters, and incidence of adverse effects."( Efficacy and Safety of Appetite-Stimulating Medications in the Inpatient Setting.
Gaviola, ML; Hossaini, R; Howard, ML; Tolar, C, 2019
)
0.51
" No serious adverse effects were observed."( Efficacy and Safety of Appetite-Stimulating Medications in the Inpatient Setting.
Gaviola, ML; Hossaini, R; Howard, ML; Tolar, C, 2019
)
0.51

Pharmacokinetics

ExcerptReferenceRelevance
" However, we still lack information on such basic pharmacokinetic parameters as the bioavailability of several of these drugs."( Clinical pharmacokinetics of endocrine agents used in advanced breast cancer.
Kvinnsland, S; Lien, EA; Lundgren, S; Lønning, PE, 1992
)
0.28
" The main source of variability in the pharmacokinetic parameters was intersubject variability; drug formulation played only a minor (and nonsignificant) role."( Pharmacokinetic evaluation of two different formulations of megestrol acetate in patients with advanced malignancies.
Cacciari, N; Camaggi, CM; Martoni, A; Pannuti, F; Pavesi, L; Robustelli della Cuna, G; Silva, A; Strocchi, E; Tedeschi, M; Zamagni, C, 1995
)
0.53
"5 mg) was administered daily to healthy women (18-50 years, n=23) for 24 days; blood samples for pharmacokinetic analysis were obtained on Day 24 and again, after a 10-day pill-free interval, on Day 35 after a single dose."( Pharmacokinetic profile of nomegestrol acetate and 17β-estradiol after multiple and single dosing in healthy women.
Gerrits, MG; Peeters, PA; Post, TM; Schnabel, PG, 2013
)
0.68
"5 h (t(max)); the mean±SD elimination half-life (t(½)) was 45."( Pharmacokinetic profile of nomegestrol acetate and 17β-estradiol after multiple and single dosing in healthy women.
Gerrits, MG; Peeters, PA; Post, TM; Schnabel, PG, 2013
)
0.68
"These data demonstrate that NOMAC/E2 has a pharmacokinetic profile consistent with once-daily dosing."( Pharmacokinetic profile of nomegestrol acetate and 17β-estradiol after multiple and single dosing in healthy women.
Gerrits, MG; Peeters, PA; Post, TM; Schnabel, PG, 2013
)
0.68
" An independent whole-body physiology-based pharmacokinetic (WB-PBPK) simulation model of NOMAC based on an independent Phase 3 dataset was used to scale NOMAC concentration-time plots to adolescents."( Prediction of nomegestrol acetate pharmacokinetics in healthy female adolescents and adults by whole-body physiology-based pharmacokinetic modelling and clinical validation.
de Greef, R; Gerrits, M; Kerbusch, T; Post, TM, 2016
)
0.78
" No statistically significant differences were observed between the adolescent and adult groups for the clinically evaluated NOMAC PK parameters [maximum concentration (Cmax), area under the curve (AUC) and half-life (t1/2)]."( Prediction of nomegestrol acetate pharmacokinetics in healthy female adolescents and adults by whole-body physiology-based pharmacokinetic modelling and clinical validation.
de Greef, R; Gerrits, M; Kerbusch, T; Post, TM, 2016
)
0.78

Compound-Compound Interactions

ExcerptReferenceRelevance
" After addition and in combination with tamoxifen this LHRH-agonist treatment caused an objective response in about half (8/17) of the patients."( Long-term LHRH-agonist treatment in metastatic breast cancer as a single treatment and in combination with other additive endocrine treatments.
Klijn, JG, 1984
)
0.27
"We have previously shown that medroxyprogesterone acetate (MPA), either alone or combined with conjugated equine estrogens (CEE), significantly decreased insulin sensitivity (SI), compared with both untreated controls and those treated with CEE alone."( Insulin sensitivity and cardiovascular risk factors in ovariectomized monkeys with estradiol alone or combined with nomegestrol acetate.
Cefalu, WT; Greaves, KA; Thomas, MJ; Wagner, JD; Williams, JK; Zhang, L, 1998
)
0.51
"To investigate the early efficacy of nedaplatin combined with megestrol in concurrent chemoradiotherapy for advanced cervical cancer."( [Analysis of the initial efficacy of nedaplatin combined with megestrol in concurrent chemoradiotherapy for advanced cervical cancer].
Ke, QH; Liu, Z; Su, XY; Yang, JY; Zhang, WT; Zhou, SQ, 2011
)
0.85

Bioavailability

ExcerptReferenceRelevance
" However, we still lack information on such basic pharmacokinetic parameters as the bioavailability of several of these drugs."( Clinical pharmacokinetics of endocrine agents used in advanced breast cancer.
Kvinnsland, S; Lien, EA; Lundgren, S; Lønning, PE, 1992
)
0.28
"Serum levels of cortisol (C), androstenedione (A), dehydroepiandrosterone (D), estrone (E1) and estradiol (E2) were chosen as parameters to compare the bioavailability of megestrol acetate (MA) and medroxyprogesterone acetate (MPA) in postmenopausal patients with advanced breast cancer."( Adrenal steroids as parameters of the bioavailability of MA and MPA.
Dikkeschei, LD; Sleijfer, DT; Tjabbes, T; van Veelen, H; Willemse, PH, 1990
)
0.47
"8 h), the absorption rate constant was the same for each of the tablets."( Evaluation of two new megestrol acetate tablet formulations in humans.
Breault, GO; Fenzl, E; Gaver, RC; Goodson, PJ; Pittman, KA; Reilly, CM,
)
0.45
"8 h) the rate of absorption was the same for each of the tablets."( Bioequivalence evaluation of new megestrol acetate formulations in humans.
Breault, GO; Fenzl, E; Gaver, RC; Goodson, PJ; Pittman, KA; Reilly, CM; Smyth, RD, 1985
)
0.55
" The trend to higher bioavailability of the new formulation was not significant, especially as compared with the dose-response data reported in the literature."( Pharmacokinetic evaluation of two different formulations of megestrol acetate in patients with advanced malignancies.
Cacciari, N; Camaggi, CM; Martoni, A; Pannuti, F; Pavesi, L; Robustelli della Cuna, G; Silva, A; Strocchi, E; Tedeschi, M; Zamagni, C, 1995
)
0.53
" The biological actions of progestins are primarily determined by their interactions with steroid receptors, and factors such as metabolism, pharmacokinetics, bioavailability and the regulation of endogenous steroid hormone biosynthesis are often overlooked."( Fourth-Generation Progestins Inhibit 3β-Hydroxysteroid Dehydrogenase Type 2 and Modulate the Biosynthesis of Endogenous Steroids.
Africander, D; Louw-du Toit, R; Perkins, MS; Snoep, JL; Storbeck, KH, 2016
)
0.43
" If a similar regulation took place in vivo, decreased bioavailability and therapeutic efficacy of NMGA-coadministered P-gp substrates could be expected."( Biphasic modulation of cAMP levels by the contraceptive nomegestrol acetate. Impact on P-glycoprotein expression and activity in hepatic cells.
Arana, MR; Domínguez, CJ; Mottino, AD; Rigalli, JP; Ruiz, ML; Tocchetti, GN; Villanueva, SSM; Weiss, J; Zecchinati, F, 2018
)
0.73

Dosage Studied

Megestrol acetate (Megace), an antiandrogen, was administered in a dosage of 80 mg daily to 6 patients with benign prostatic hypertrophy (BPH) for 4 to 25 days prior to transurethral resection of the prostate (TURP) Plasma levels of megestrolacetat averaged 600 ng/mL in the first month of therapy and decreased to approximately 400 ng/ML at 8 and 12 weeks.

ExcerptRelevanceReference
" The 1st group received megestranol in a contraceptive dosage; the 2nd group was administered half of the contraceptive dosage of megestranol; the 3d group received spasmolitin, the 4th a combination of megestranol and spasmolitin, and the 5th group served as a control."( [Nature of the ovulation and the state of the preimplantation fetuses in the experimental administration of hormonal and neurotropic agents].
Korkhov, VV; Nikitin, AI; Nikitina, GV, 1978
)
0.26
" Since the urodynamic evidence does indicate a possibility of a positive effect, it appears reasonable to investigate further using a different protocol - perhaps a higher dosage and/or a more controlled test population."( Megestrol acetate in treatment of benign prostatic hypertrophy.
Donker, PJ; Donkervoort, T; Ritter, RC; Sterling, AM; Van Ness, J; Zinner, NR, 1975
)
1.7
"Megestrol acetate (Megace), an antiandrogen, was administered in a dosage of 80 mg daily to 6 patients with benign prostatic hypertrophy (BPH) for 4 to 25 days prior to transurethral resection of the prostate (TURP)."( Effect of megestrol acetate (Megace) on steroid metabolism and steroid-protein binding in the human prostate.
Albert, J; Cantor, T; Geller, J; Geller, S; Lopez, D; Yen, S, 1976
)
2.1
" The decreased glucose tolerance may be due as much to dosage levels as to any metabolic characteristics of the various oestrogens prescribed."( Effect of hormone replacement therapy on glucose tolerance in postmenopausal women.
Chakravarti, S; Oram, DH; Studd, JW; Thom, M, 1977
)
0.26
" Over the dosage range studied, the effects of the two kinds of estrogen were indistinguishable."( Comparative studies of the ethynyl estrogens used in oral contraceptives. VII. Effects with and without progestational agents on ultracentrifugally fractionated plasma lipoproteins in humans, baboons, and beagles.
Chenault, CB; de la Peña, A; Dozier, TS; Goldzieher, JW; Kraemer, DC, 1978
)
0.26
" Effects of the 2 kinds of estrogens were indistinguishable over the dosage range studied."( Comparative studies of the ethynyl estrogens used in oral contraceptives. VII. Effects with and without progestational agents on ultracentrifugally fractionated plasma lipoproteins in humans, baboons, and beagles.
Chenault, CB; de la Peña, A; Dozier, TS; Goldzieher, JW; Kraemer, DC, 1978
)
0.26
" This decrease varied with the type of progestogen used in continuous low dosage therapy."( The effect of combination and low dose progestogen oral contraceptives on serum lipids.
Donde, UM; Virkar, K, 1975
)
0.25
" In the intermediate dosage range, both factors contributed to the decreased ratio."( Effect of 17alpha-ethinylestradiol on biliary excretion of bile acids.
Watanabe, H, 1975
)
0.25
" Dosage of megestrolacetat for cows and heifers are discussed."( [Megestrolacetat applied for oestrusinduction and oestrussynchronization in heifers (author's transl)].
Benjaminsen, E, 1975
)
1.55
" Dose-response studies have demonstrated increasing efficacy with increasing doses of megestrol acetate from 160 to 800 mg/day."( Nutrition in advanced cancer: anorexia as an outcome variable and target of therapy.
Ashley, J; Halpert, C; Heber, D; Tchekmedyian, NS,
)
0.35
" It is hoped that these results will provide a definitive answer to the dose-response issue for breast cancer."( Potential applications of high-dose megestrol acetate in breast cancer.
Abrams, JS; Aisner, J; Gutheil, J, 1992
)
0.56
" No correlation between megestrol acetate dosage and weight gain was found, but there was a tendency for increased weight in more patients taking high-dose megestrol acetate."( Risks and benefits of various therapies for cancer anorexia.
Schmoll, E, 1992
)
0.59
" Ongoing clinical trials are evaluating the dose-response relationship of megestrol acetate for these clinical problems and whether megestrol acetate will improve the survival of patients at risk for developing cancer anorexia/cachexia."( Megestrol acetate for anorexia and cachexia.
Jensen, M; Johnson, PA; Loprinzi, CL, 1992
)
1.96
"A dose-response relationship has been suggested for medroxyprogesterone acetate in the treatment of advanced breast cancer."( A phase I/II study of high-dose megestrol acetate in the treatment of metastatic breast cancer.
Abrams, JS; Aisner, J; Parnes, HL; Tait, N; Tchekmedyian, NS, 1991
)
0.56
" The progestogen was administered from day 7 to 25 of the cycle during six cycles at a dosage (5 mg/d) known to inhibit ovulation."( Effects of nomegestrol acetate (5 mg/d) on hormonal, metabolic and hemostatic parameters in premenopausal women.
Basdevant, A; Conard, J; Degrelle, H; Guyene, TT; Pelissier, C; Thomas, JL, 1991
)
0.65
" Doubling the dose of either drug did not enhance hormone suppression, indicating that the drug dosage is maximally suppressive."( Adrenal steroids as parameters of the bioavailability of MA and MPA.
Dikkeschei, LD; Sleijfer, DT; Tjabbes, T; van Veelen, H; Willemse, PH, 1990
)
0.28
" Many investigators have reported that progestogen with high dosage shows a good response to advanced endometrial cancer."( [Therapy of advanced endometrial cancer].
Okada, H; Yamamoto, T, 1990
)
0.28
" Attempts to further enhance the role of progestins have centered on dosage escalation, based on European data suggesting a dose-response effect."( Current status of high-dose progestins in breast cancer.
Abrams, JS; Aisner, J; Parnes, H, 1990
)
0.28
" There is apparently a dose-response between megestrol acetate and breast cancer, along with a response dependent on the number and type of estrogen and progestin receptors."( Megestrol acetate: clinical experience.
Canetta, R; Kelley, S; Nicaise, C; Rozencweig, M; Schacter, L; Smaldone, L, 1989
)
1.98
" Effects on cortisol persisted for two weeks after MA dosage ceased."( Comparative effects of proligestone and megestrol acetate on basal plasma glucose concentrations and cortisol responses to exogenous adrenocorticotrophic hormone in cats.
Church, DB; Emslie, DR; Middleton, DJ; Watson, AD, 1989
)
0.54
" This is a follow-up report on the 434 women who used this 'optional' dosage of compound by before-and-after comparisons and by comparisons with two other groups of women: 41 women who were given the compound with the same dosage combination but with microencapsular coat dissolved, and 20-30 women who were using a non-steroidal contraceptive method such as IUDs, barrier or rhythm methods."( A follow-up study of the efficacy and safety of injectable microencapsulated megestrol acetate and a discussion on its contraceptive mechanism.
Han, ZY; Xiao, RQ, 1985
)
0.5
" Although the dose-dependent mode of actions of MPA have been extensively clarified, there is still some uncertainty regarding the mode of actions and dosage of MA."( [Megestrol acetate in various doses in the treatment of metastatic breast carcinoma--clinical and endocrinologic studies].
Blossey, HC; Emrich, D; Nagel, GA; Wander, HE, 1985
)
1.18
" Plasma levels of megestrol acetate averaged 600 ng/mL in the first month of therapy and decreased to approximately 400 ng/mL at 8 and 12 weeks, after the drug dosage had been reduced."( High-dose megestrol acetate therapy of ovarian carcinoma: a phase II study by the Northern California Oncology Group.
Ballon, SC; Brandt, AE; Christman, JE; Ehsan, MN; Evans, TL; Scudder, SA; Sikic, BI; Soriero, OM; Suey, L, 1986
)
1.01
"A dose-response relationship has long been suspected for progestin compounds in the treatment of breast cancer, but only recently have trials been implemented to investigate this issue."( High-dose megestrol acetate in the treatment of advanced breast cancer.
Abrams, J; Aisner, J; Tait, N; Tchekmedyian, NS, 1988
)
0.68
" Sequential studies suggest a steep dose-response relationship for medroxyprogesterone."( High-dose megestrol acetate for the treatment of advanced breast cancer: dose and toxicities.
Aisner, J; Moody, M; Tait, N; Tchekmedyian, NS, 1987
)
0.68
"The optimal dose of progesterone compounds for the treatment of breast cancer is unknown, but there is evidence to suggest a dose-response curve."( High-dose megestrol acetate in the treatment of postmenopausal women with advanced breast cancer.
Aisner, J; Tait, N; Tchekmedyian, NS, 1986
)
0.67
"5 mg dosage is too strong, and its effect exceeds the desired contraceptive level as well as disturbs ovarian activity."( [Personal experiences with Minitrol].
Cervenka, J; Houdek, J; Pelák, Z, 1973
)
0.25
"To find a suitable contraceptive combination 11 dosage combinations of estrogen and megestrol acetate were studied clinically."( The use of conjugated oestrogen in oral contraception.
Kaivola, S; Timonen, S; Widholm, O, 1974
)
0.48
" Serum percentage of iodine uptake, total thyroxine, free thoraxine, and weight changes in 38 women taking combination oral contraceptives and 27 taking low dosage progestagens were studied."( Thyroid functions of women taking oral contraceptives.
Barsivala, V; Virkar, K, 1974
)
0.25
" Studies are in progress to determine the highest intrauterine dosage which will cause no systemic effect but should make nidation impossible and thus protect completely against intrauterine pregnancy without the risks of other routes of aadministration."( Microdose intrauterine progestagen associated with intrauterine contraceptive devices.
Horne, HW; Scott, JM; Underwood, RH,
)
0.13
"A comparative clinical study was undertaken by the Sichuan Cooperative Research Group for Microencapsulated Contraceptives to assess the efficacy of intramuscular microencapsulated megestrol compound as a long-acting contraceptive and to find the optimal dosage as regards efficacy, side effects and menstrual irregularities."( Clinical evaluation of intramuscular injection of microencapsulated compound megestrol acetate.
Han, ZY; Xiao, RQ, 1984
)
0.69
" There is a tendency towards an increased response-rate with increased dosage of progestin, in both endometrial and breast carcinoma, while the route of administration appears to be of minor importance."( Progestin therapy of endometrial, breast and ovarian carcinoma. A review of clinical observations.
Kauppila, A, 1984
)
0.27
" The dosage schedule was 5 mg orally per day per cat for seven days, then 5 mg every three days for 21 days."( The use of megestrol acetate in some feline dermatological problems.
Chalifoux, A; Gosselin, Y; Papageorges, M, 1981
)
0.65
" The dosage used was 5 mg a day for seven days followed by 5 mg every three days for 21 days."( [The use of megestrol acetate to stop urine spraying in castrated male cats (author's transl)].
Chalifoux, A; Gosselin, Y, 1981
)
0.64
" Further differentiation of 400 vs 800 mg arms was seen in the BACRI-7 results, consistent with dose-response improvements in weight and lean body mass changes."( The Bristol-Myers Anorexia/Cachexia Recovery Instrument (BACRI): a brief assessment of patients' subjective response to treatment for anorexia/cachexia.
Browder, HP; Cella, DF; Lloyd, S; VonRoenn, J, 1995
)
0.29
" The trend to higher bioavailability of the new formulation was not significant, especially as compared with the dose-response data reported in the literature."( Pharmacokinetic evaluation of two different formulations of megestrol acetate in patients with advanced malignancies.
Cacciari, N; Camaggi, CM; Martoni, A; Pannuti, F; Pavesi, L; Robustelli della Cuna, G; Silva, A; Strocchi, E; Tedeschi, M; Zamagni, C, 1995
)
0.53
" Toxicity was tolerable, and more than 80% of ideal dosing was achieved during the first two cycles of treatment."( Megestrol melanoma study.
Garrison, M; Nathanson, L,
)
1.57
" There may be a trend toward a dose-response effect, which represents a suitable topic for a future prospective trial."( Hormonal palliation of chemoresistant ovarian cancer: three consecutive phase II trials of the Mid-Atlantic Oncology Program.
Ahlgren, JD; Alt, D; Ellison, NM; Gottlieb, RJ; Laluna, F; Lokich, JJ; Sinclair, PR; Ueno, W; Wampler, GL; Yeung, KY, 1993
)
0.29
" The progestogen was administered from day 5 to day 24 of the cycle, over six consecutive cycles, at a dosage (5 mg/d) known to inhibit ovulation."( Effects of nomegestrol acetate on carbohydrate metabolism.
Choisy, H; Dorangeon, P; Hazard, MC; Lumbroso, M; Thomas, JL,
)
0.5
" A statistically significant correlation between the ratio of body weight at 3 weeks/initial weight (weight index) and the percentage of the 24-h dosing interval that megestrol acetate concentrations exceeded a 300-ng/ml threshold was observed."( Pharmacologic evaluation of megestrol acetate oral suspension in cachectic AIDS patients.
Dudley, MN; Fisher, AE; Graham, KK; Mikolich, DJ; Posner, MR, 1994
)
0.78
" The cats given MA (n = 7) developed significant suppression of plasma ACTH concentrations and hyperinsulinaemia during treatment and for two to four weeks after MA dosage ceased."( Effects of proligestone and megestrol on plasma adrenocorticotrophic hormone, insulin and insulin-like growth factor-1 concentrations in cats.
Church, DB; Emslie, DR; Middleton, DJ; Tan, K; Watson, AD; Wong, D, 1994
)
0.58
"The impact of the side effects of megestrol acetate on the quality of life of noncachectic women with advanced breast cancer was studied in a dose-response clinical trial of the Cancer and Leukemia Group B (CALGB 8741)."( Effect of megestrol acetate on quality of life in a dose-response trial in women with advanced breast cancer. The Cancer and Leukemia Group B.
Abrams, J; Aisner, J; Canellos, GP; Cooper, MR; Herndon, JE; Hollis, DR; Kornblith, AB; Lyss, AP; Phillips, CA; Zuckerman, E, 1993
)
0.97
" Megestrol acetate has been reported to increase appetite and body weight, and a linear dose-response relation for doses from 160 up to 1600 mg/day has been proposed."( Low dose megestrol acetate can abrogate cachexia in advanced tumor patients receiving systemic interferon-alpha and/or interleukin-2 based antineoplastic therapy.
Ackermann, M; Atzpodien, J; Kirchner, H, 1993
)
1.61
"The data demonstrate that there is a positive dose-response effect for megestrol acetate on appetite stimulation (P < or = ."( Phase III evaluation of four doses of megestrol acetate as therapy for patients with cancer anorexia and/or cachexia.
Athmann, LM; Goldberg, RM; Hatfield, AK; Loprinzi, CL; Mailliard, JA; Michalak, JC; Morton, RF; Schaid, DJ; Tschetter, LK, 1993
)
0.79
"The positive dose-response effect that we observed for megestrol acetate on appetite stimulation supports both our prestudy hypothesis and other available literature."( Phase III evaluation of four doses of megestrol acetate as therapy for patients with cancer anorexia and/or cachexia.
Athmann, LM; Goldberg, RM; Hatfield, AK; Loprinzi, CL; Mailliard, JA; Michalak, JC; Morton, RF; Schaid, DJ; Tschetter, LK, 1993
)
0.8
" dosing with 100 mg/kg CPA once a week for 6 successive weeks induced, as compared to controls, a significant increase in the number and area of gamma-glutamyltranspeptidase-positive foci."( Induction of micronuclei and initiation of enzyme-altered foci in the liver of female rats treated with cyproterone acetate, chlormadinone acetate, or megestrol acetate.
Allavena, A; Brambilla Campart, G; Brambilla, G; Ghia, M; Martelli, A; Mereto, E, 1996
)
0.49
" Moreover, data concerning the dose escalation of MA dosage in unresponsive patients suggest that a step by step increase in MA dosage could be the best way of administering MA for the management of ACS and that the increase of MA dosage over 480 mg day-1 will probably be useless in the vast majority of cases."( Prospective randomised trial of two dose levels of megestrol acetate in the management of anorexia-cachexia syndrome in patients with metastatic cancer.
Gebbia, N; Gebbia, V; Testa, A, 1996
)
0.55
" Tissue distribution at 1, 2, and 4 h and excretion of NOMAC into bile, urine, and feces after dosing were investigated."( Pharmacokinetics, tissue distribution, and excretion of nomegestrol acetate in female rats.
Cao, L; Chen, X; Huang, Q; Riviere, JE; Zhu, Y, 2015
)
0.66
" Blood samples were obtained for PK analysis, and concentrations of NOMAC, E2 and its metabolite estrone (E1) were determined for up to 129h following dosing to obtain PK data."( Prediction of nomegestrol acetate pharmacokinetics in healthy female adolescents and adults by whole-body physiology-based pharmacokinetic modelling and clinical validation.
de Greef, R; Gerrits, M; Kerbusch, T; Post, TM, 2016
)
0.78
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Roles (5)

RoleDescription
contraceptive drugA chemical substance that prevents or reduces the probability of conception.
antineoplastic agentA substance that inhibits or prevents the proliferation of neoplasms.
appetite enhancerA drug which increases appetite.
progestinA synthetic progestogen.
synthetic oral contraceptiveAn oral contraceptive which owes its effectiveness to synthetic preparation.
[role information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Drug Classes (4)

ClassDescription
20-oxo steroidAn oxo steroid carrying an oxo group at position 20.
17alpha-hydroxy steroidThe alpha-stereoisomer of 17-hydroxy steroid.
3-oxo-Delta(4) steroidA 3-oxo steroid conjugated to a C=C double bond at the alpha,beta position.
tertiary alpha-hydroxy ketoneAn alpha-hydroxy ketone in which the carbonyl group and the hydroxy group are linked by a carbon bearing two organyl groups.
[compound class information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Bioassays (2)

Assay IDTitleYearJournalArticle
AID1474166Liver toxicity in human assessed as induction of drug-induced liver injury by measuring severity class index2016Drug discovery today, Apr, Volume: 21, Issue:4
DILIrank: the largest reference drug list ranked by the risk for developing drug-induced liver injury in humans.
AID1474167Liver toxicity in human assessed as induction of drug-induced liver injury by measuring verified drug-induced liver injury concern status2016Drug discovery today, Apr, Volume: 21, Issue:4
DILIrank: the largest reference drug list ranked by the risk for developing drug-induced liver injury in humans.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (1,056)

TimeframeStudies, This Drug (%)All Drugs %
pre-1990629 (59.56)18.7374
1990's265 (25.09)18.2507
2000's71 (6.72)29.6817
2010's71 (6.72)24.3611
2020's20 (1.89)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 86.25

According to the monthly volume, diversity, and competition of internet searches for this compound, as well the volume and growth of publications, there is estimated to be very strong demand-to-supply ratio for research on this compound.

MetricThis Compound (vs All)
Research Demand Index86.25 (24.57)
Research Supply Index7.19 (2.92)
Research Growth Index4.35 (4.65)
Search Engine Demand Index158.82 (26.88)
Search Engine Supply Index2.02 (0.95)

This Compound (86.25)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials204 (18.20%)5.53%
Reviews93 (8.30%)6.00%
Case Studies86 (7.67%)4.05%
Observational7 (0.62%)0.25%
Other731 (65.21%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Clinical Trials (73)

Trial Overview

TrialPhaseEnrollmentStudy TypeStart DateStatus
Prospective Clinical Study of the Effect of Thalidomide Combined With Megestrol Acetate on Lymphocyte, Inflammatory Factor Regulation and Nutritional Status in Patients With Advanced Malignant Tumors [NCT03777930]Phase 4200 participants (Anticipated)Interventional2018-12-10Not yet recruiting
A Randomized, Open Label, Single Dose, Cross-over, Phase I Trial to Investigate Safety and Pharmacokinetics of DW-ES(B) and Megace® Under Fed Conditions in Healthy Male Volunteers [NCT01589562]Phase 128 participants (Anticipated)Interventional2012-04-30Completed
A Phase 2, Single Arm, Two Period Study of Sodium Cridanimod in Conjunction With Progestin Therapy in Patients With Endometrial Carcinoma [NCT03077698]Phase 225 participants (Actual)Interventional2017-06-14Terminated(stopped due to The study was discontinued due to a change in development strategy and not due safety concern.)
Megestrol Acetate Plus LNG-IUS to Megestrol Acetate or LNG-IUS in Young Women With Endometrial Atypical Hyperplasia [NCT03241888]Phase 2/Phase 3180 participants (Actual)Interventional2017-07-04Completed
Single Site, Open-label, Randomized, Two Treatments, Two Periods, Two Sequences, Crossover Single-dose Trial to Investigate the Bioequivalence of Two Oral Formulations of a Fixed-dose Combination Tablet Containing 1.5 mg Estradiol and 2.5 mg Nomegestrol A [NCT03749733]Phase 10 participants (Actual)Interventional2019-10-31Withdrawn(stopped due to Sponsor decision)
Evidence-based Medical Research on the Treatment of Children's Rapid Progressive Central Precocious Puberty With Integrative Chinese and Western Medicine [NCT03963752]Phase 4164 participants (Anticipated)Interventional2019-08-15Recruiting
Levonorgestrel-Releasing Intrauterine System (LNG-IUS) in the Management of Atypical Endometrial Hyperplasia: A Non-Inferiority Study [NCT04897217]Phase 30 participants (Actual)Interventional2023-06-30Withdrawn(stopped due to PI decision)
Randomized, Double-blind Clinical Trial of the Use of Mirtazapine Versus Megestrol for the Control of Anorexia-cachexia in Cancer Patients in Palliative Care. [NCT03283488]Phase 252 participants (Actual)Interventional2019-03-26Completed
Megestrol Acetate Plus Rosuvastatin in Young Women With Atypical Endometrial Hyperplasia [NCT04491682]Phase 2/Phase 336 participants (Actual)Interventional2020-09-01Completed
Phase II Trial of Progressive Resistance Training With Megestrol Acetate for the Treatment of Cancer-Related Weight Loss [NCT00004912]Phase 20 participants Interventional2000-01-31Completed
Randomised Phase II Clinical Trial PIONEER- A Pre-operative wIndOw Study of Letrozole Plus PR Agonist (Megestrol Acetate) Versus Letrozole aloNE in Post-menopausal Patients With ER-positive Breast Cancer [NCT03306472]Phase 2189 participants (Anticipated)Interventional2017-07-20Recruiting
A Randomized Phase II Trial of Temsirolimus (NCI-Supplied Agent, NSC # 683864) or the Combination of Hormonal Therapy Plus Temsirolimus in Women With Advanced, Persistent, or Recurrent Endometrial Carcinoma [NCT00729586]Phase 273 participants (Actual)Interventional2008-09-30Completed
A Randomized, Open Label, Single Dose, Cross-over, Phase I Trial to Investigate Safety and Pharmacokinetics of Apetrol ES and Megace® Under Fasting and Fed Conditions in Healthy Male Volunteers [NCT02446353]Phase 179 participants (Actual)Interventional2010-04-30Completed
Surgical Window of Opportunity Study of Megestrol Acetate Compared With Megestrol Acetate and Metformin for Endometrial Intraepithelial Neoplasia. [NCT04576104]Phase 250 participants (Anticipated)Interventional2021-09-17Recruiting
A Phase IB and Randomized Phase II Trial of Megestrol Acetate With or Without Ipatasertib in Recurrent or Metastatic Endometrioid Endometrial Cancer [NCT05538897]Phase 1/Phase 296 participants (Anticipated)Interventional2023-03-31Suspended(stopped due to Other - Review of safety data of Phase IB)
Prospective Trial of Conservative Management of Atypical Endometrial Hyperplasia and Well to Moderately Differentiated Endometrial Carcinoma Using Megestrol Acetate [NCT00483327]Phase 231 participants (Actual)Interventional2007-06-30Completed
Gonadotropin-releasing Hormone Agonist Combined With Letrozole Compared With Megestrol Acetate or Medroxyprogesterone Acetate Alone as Fertility-sparing Treatment in Early Endometrial Cancer [NCT05247268]Phase 2104 participants (Anticipated)Interventional2022-03-11Recruiting
A Phase III Trial of Placebo Versus Megestrol Acetate 20 MG/Day Versus Megestrol Acetate 40 MG/Day as Treatment for Symptoms of Ovarian Failure in Women Treated for Breast Cancer: SWOG Study S9626 [NCT00005975]Phase 3288 participants (Actual)Interventional1998-04-30Completed
A Phase II International Multicentre Randomised Open Label Study of Oral Steroid Sulphatase Inhibitor BN83495 Versus Megestrol Acetate (MA) in Women With Advanced or Recurrent Endometrial Cancer [NCT00910091]Phase 273 participants (Actual)Interventional2009-08-31Completed
Weight Management Plus Levonorgestrel Intrauterine System or Megestrol Acetate in Endometrial Atypical Hyperplasia: Multiple Single-arm, Prospective and Open-label Clinical Study [NCT05316493]Phase 2/Phase 3172 participants (Anticipated)Interventional2022-06-13Recruiting
Weight Management Plus Megestrol Acetate in Early-stage Endometrioid Carcinoma: Two Single-arm, Prospective and Open-label Clinical Study [NCT05316467]Phase 2/Phase 389 participants (Anticipated)Interventional2022-05-01Recruiting
The Traditional Chinese Medicine Department of Xin Qiao Hospital [NCT02619266]Phase 2/Phase 3160 participants (Anticipated)Interventional2015-12-31Recruiting
A Randomized Phase II Trial of Ridaforolimus (AP23573; MK-8669) Compared to Progestin or Chemotherapy in Female Adult Patients With Advanced Endometrial Carcinoma [NCT00739830]Phase 2130 participants (Actual)Interventional2008-08-31Completed
An Open-Label, Single-Dose Study to Assess the Effect of Renal Impairment on the Pharmacokinetic Characteristics, Safety, and Tolerability of Megestrol Acetate [NCT00637403]Phase 17 participants (Actual)Interventional2006-05-31Terminated(stopped due to Difficulty finding the required subject population)
A Randomized, Open-label, Single-dose, Cross-over Study to Investigate Safety and Pharmacokinetics of Megace F and Megace OS Under Fasting and Fed Conditions in Healthy Male Volunteers [NCT01397214]Phase 1103 participants (Actual)Interventional2011-07-31Completed
A Phase III, Double-Blind, Randomized Study Of The Effect Of Megestrol Acetate On Weight And Health Related Quality Of Life In Head And Neck Cancer Patients Receiving Radiation Therapy [NCT00006799]Phase 313 participants (Actual)Interventional2000-10-01Completed
A Phase II Head-to-Head Comparison of Fertility-Sparing Approaches to Treat Complex Atypical Hyperplasia of the Edometrium: Megestrol Versus Levonorgestrel-Releasing Intrauterine System (LNG-IUS) [NCT01943058]Phase 20 participants (Actual)Interventional2014-03-31Withdrawn(stopped due to Lack of funding)
Mirtazapine Versus Megestrol Acetate in Treatment of Anorexia-cachexia in Advanced Cancer Patients: A Randomized, Double-Blind Trail. [NCT05380479]Phase 280 participants (Anticipated)Interventional2022-06-01Recruiting
Megestrol Acetate Plus Rosuvastatin in Young Women With Early Endometrial Carcinoma [NCT04491643]Phase 248 participants (Anticipated)Interventional2020-09-01Recruiting
A Randomized Phase II Evaluation of Continuous Progestin Therapy vs. Sequential Progestin Therapy in the Treatment of Endometrial Intraepithelial Neoplasia (EIN) From a Referred Cohort of Atypical Endometrial Hyperplasia (AEH) or EIN Patients That Desire [NCT00503581]Phase 29 participants (Actual)Interventional2007-07-31Terminated
Megestrol Acetate for the Improvement of Quality of Life in Esophageal Cancer With Chemoradiotherapy [NCT02644408]Phase 3184 participants (Actual)Interventional2014-10-01Completed
A Phase II Randomized Study to Assess the Benefit of a Metronomic Chemotherapy by Cyclophosphamide Versus Megestrol in Palliative Cancer [NCT00420563]Phase 288 participants (Actual)Interventional2006-09-30Completed
Single-center, Randomized, Open-label, 2-way Crossover Bioavailability Study, Evaluating the Effect of Food on Megace ES (Megestrol Acetate 625 mg/5 mL Oral Suspension) Following a 625 mg Dose in Healthy Subjects [NCT00638079]Phase 124 participants (Actual)Interventional2006-06-30Completed
The Effect of Megestrol Acetate on Grade 2 Endometrioid Endometrial Cancer in Patients Waiting for Definitive Surgery, a Prospective Trial [NCT05332483]Phase 15 participants (Actual)Interventional2022-07-05Terminated(stopped due to Slow enrollment)
iKanEat: A Randomized-controlled, Multi-center Trial of Megestrol for Chronic Oral Food Refusal in Children 9 Months to 9 Years 0 Months of Age [NCT03815019]Phase 460 participants (Anticipated)Interventional2019-08-15Recruiting
Follow-up of the Study 971-ONC-0028-080: Exemestane Versus Megestrol Acetate In Postmenopausal Patients With Metastatic Breast Cancer, Failing Anti-Estrogens: An Open-Label, Randomized, Parallel-Group, Phase III Comparative Study [NCT01237327]Phase 384 participants (Actual)Interventional2001-11-30Completed
Megestrol Acetate Versus Liraglutide Plus Megestrol Acetate in Obese Women With Endometrial Atypical Hyperplasia: A Randomized Controlled Pilot Clinical Study [NCT04683237]Phase 2/Phase 30 participants (Actual)Interventional2021-03-20Withdrawn(stopped due to Based on our latest research results, we will revise the protocol and design a better study. Since no participants are enrolled till now, we withdraw this study.)
Comparing Metformin Plus Megestrol Acetate With Megestrol Acetate Alone as a Fertility-sparing Treatment in Patients With Atypical Endometrial Hyperplasia [NCT04607252]Phase 2/Phase 312 participants (Actual)Interventional2021-01-11Terminated(stopped due to Our clinical trial NCT03241888 showed LNG-IUS had a better treatment efficacy than Megestrol Acetate (MA) alone. The median CR time for MA group, LNG-IUS group and MA plus LNG-IUS group was 7.0±0.3 months, 4.4±1.0 months and 5.7±1.2 months.)
The Effect of Cyproheptadine Hydrochloride (Periactin) and Megestrol Acetate (Megace) on Weight in Children With Cancer/Treatment Related Cachexia [NCT00066248]Phase 270 participants (Actual)Interventional2003-06-30Completed
A Phase III Randomized Study Comparing The Effects Of Oxandrolone (Oxandrin) And Megestrol Acetate (Megace) On Lean Body Mass, Weight, Body Fat, And Quality Of Life In Patients With Solid Tumors And Weight Loss Receiving Chemotherapy [NCT00070148]Phase 3155 participants (Actual)Interventional2004-03-01Completed
Randomized Trial,Comparative With Placebo, Double Blind, to Evaluate the Effect of the Treatment With 320 mg/d of Megestrol Acetate in Patients With Severe Chronic Obstructive Pulmonary Disease (COPD) and Loss of Body Weight. Pilot Study [NCT00507949]Phase 240 participants (Anticipated)Interventional2006-10-31Completed
Multicenter, Double Blind, Randomized, Clinical Trial, Controlled With Placebo, to Evaluate the Effect of the Treatment With 320 mg/Day of Megestrol Acetate During 24 Weeks in the Weight Loss in Mixed Dementia Patients. [NCT00503516]Phase 2/Phase 339 participants (Actual)Interventional2007-06-30Terminated(stopped due to Difficulties to recruit the patients following the inclusion criteria)
Randomized Phase III Crossover Trial of Chemotherapy (Doxorubicin/Cisplatin/Paclitaxel and G-CSF) Versus Hormonal Therapy (Tamoxifen/Megestrol Acetate) in Patients With Stage III & IV or Recurrent Endometrial Cancer [NCT00016341]Phase 30 participants Interventional2001-05-31Terminated
Randomized Double Blind Trial Of Megestrol Acetate Versus Placebo For The Treatment Of Inoperable Hepatocellular Carcinoma [NCT00041275]Phase 3300 participants (Anticipated)Interventional2002-05-31Completed
Phase III Double-Blind, Placebo-Controlled Randomized Comparison of Megestrol Acetate (Megace) Versus an N-3 Fatty Acid (EPA) Enriched Nutritional Supplement Versus Both for the Treatment of Cancer Cachexia and Anorexia [NCT00031707]Phase 3429 participants (Actual)Interventional2000-03-31Completed
A Phase III, Double-Blind, Randomized Study of the Effect of Megestrol Acetate on Weight and Health Related Quality of Life in Lung Cancer Patients Receiving Thoracic Radiation Therapy [NCT00031785]Phase 325 participants (Actual)Interventional2000-09-01Completed
Open-Label Randomized Phase II Trial of Megestrol Acetate With or Without Pterostilbene in Patients With Endometrial Cancer Scheduled for Hysterectomy [NCT03671811]Phase 244 participants (Actual)Interventional2019-01-21Active, not recruiting
A Phase II Study Assessing the Efficacy of Prophylaxis Use of Megestrol Acetate Against Cancer-related Critical Body Weight Loss in Patients With Head and Neck Cancer Who Receiving Concurrent Chemoradiotherapy [NCT02980653]Phase 2105 participants (Anticipated)Interventional2015-05-31Recruiting
Evaluation of the Time Course of Adrenal Suppression and Adrenal Recovery After Ingestion of Megestrol Acetate [NCT00575029]7 participants (Actual)Interventional2004-04-30Completed
Treatment of Cancer Anorexia-cachexia Syndrome (CACS) With Mirtazapine and Megestrol Acetate [NCT01501396]Phase 20 participants (Actual)Interventional2013-09-30Withdrawn
Phase II-III Randomized Double-Blind Study Comparing Megestrol Acetate at 100, 400, and 800 mg/Day, and Placebo in AIDS Patients With Anorexia and Cachexia [NCT00002300]Phase 20 participants InterventionalCompleted
Comparison of the Efficacy and Safety of 5-HT3 Receptor Antagonist, Dexamethasone or Megestrol Acetate Dispersible Tablets in the Control of Nausea and Vomiting Induced by Highly Emetogenic Chemotherapy: a Prospective, Randomized Controlled Phase II Clini [NCT04430361]Phase 2120 participants (Anticipated)Interventional2018-09-07Recruiting
Megestrol Acetate Plus Metformin to Megestrol Acetate in Patients With Endometrial Atypical Hyperplasia or Early Stage Endometrial Adenocarcinoma [NCT01968317]Phase 2150 participants (Actual)Interventional2013-10-31Completed
Phase III Randomized Double-Blind Study Comparing Megestrol Acetate at 800 mg/Day, and Placebo in AIDS Patients With Anorexia and Cachexia [NCT00002067]Phase 30 participants InterventionalCompleted
Megestrol Acetate For Failure To Thrive In Pediatric HIV [NCT00002182]25 participants InterventionalCompleted
Phase II Trial of Sequential High-Dose Alkylating Agents in Metastatic Breast Cancer [NCT00002680]Phase 240 participants (Actual)Interventional1994-02-28Completed
Phenytoin for Memory Impairment Secondary to Megestrol [NCT02595723]Phase 421 participants (Actual)Interventional2015-07-31Completed
A Randomized, Double-blind, Placebo-controlled Study of Megestrol Acetate Concentrated Suspension for the Treatment of Cancer-associated Anorexia in Subjects With Cancer of Multiple Types [NCT00637806]Phase 34 participants (Actual)Interventional2006-06-30Terminated(stopped due to Difficulty finding the required patient population)
A Randomized, Double-blind, Placebo-controlled Study of Megestrol Acetate Concentrated Suspension for the Treatment of Cancer-associated Anorexia in Subjects With Lung or Pancreatic Cancer [NCT00637728]Phase 35 participants (Actual)Interventional2006-06-30Terminated(stopped due to Difficulty finding the required patient population)
A Randomized, Open-labeled, Pilot Study Comparing Weight Gain in Adults With AIDS-related Wasting Given Either Megestrol Acetate Oral Suspension Nanocrystal Dispersion (MA-NCD) or Megestrol Acetate Oral Suspension (Megace) [NCT00637572]Phase 263 participants (Actual)Interventional2004-12-31Completed
A Phase II, Randomized-Controlled, Multicenter Trial of Amitriptyline for Chronic Oral Food Refusal in Children 9 Months to 8 Years of Age [NCT01206478]Phase 221 participants (Actual)Interventional2010-08-31Completed
[NCT00004664]69 participants Interventional1995-06-30Completed
A Phase I/II Study to Evaluate Single Agent and Combination Therapy With Megestrol Acetate and Dronabinol for the Treatment of HIV-Wasting Syndrome [NCT00000737]Phase 156 participants InterventionalCompleted
Double-Blind Randomized Comparison Phase II Trial of Megestrol Acetate and Testosterone Enanthate in Combination Versus Megestrol Acetate Plus Testosterone Enanthate Placebo in Human Immunodeficiency Virus (HIV)-Associated Wasting. [NCT00001079]Phase 280 participants InterventionalCompleted
A Randomized Megestrol Acetate/Placebo Controlled Trial in Pediatric Patients With Malignancies With Weight Loss/Anorexia [NCT01200602]Phase 21 participants (Actual)Interventional2011-03-31Terminated(stopped due to The study closed due to slow accrual.)
Phase IV Study on the Safety and Efficacy of Megace Oral Suspension in HIV-Positive Females [NCT00002345]Phase 440 participants InterventionalCompleted
Phase I/II Study of High-Dose Megestrol in Breast or Endometrial Carcinoma or Mesothelioma [NCT00002465]Phase 1/Phase 20 participants Interventional1987-12-31Active, not recruiting
Prospective, Phase II Study to Evaluate the Efficacy of Addition of Progesterone to Standard Chemotherapy According to Etoposide-Doxorubicin-Cisplatin Scheme Plus Mitotane (EDP-M) in Patients With Advanced Adrenocortical Carcinoma (ACC) [NCT05913427]Phase 280 participants (Anticipated)Interventional2022-06-08Recruiting
A Pilot Study Evaluating Megestrol Acetate Modulation in Advanced Breast Cancer With Positive Hormonal Receptor [NCT03024580]Phase 220 participants (Anticipated)Interventional2017-03-06Recruiting
A Randomized Phase III Trial of Olanzapine Versus Megestrol Acetate for Cancer-Associated Anorexia [NCT04939090]Phase 3360 participants (Anticipated)Interventional2021-10-15Recruiting
Refining Adjuvant Treatment IN Endometrial Cancer Based On Molecular Features: the p53abn-RED Trial, the MMRd-GREEN Trial, the NSMP-ORANGE Trial and the POLEmut-BLUE Trial [NCT05255653]Phase 2/Phase 31,615 participants (Anticipated)Interventional2021-11-11Recruiting
Megestrol Acetate Plus LNG-IUS to Megestrol Acetate in Young Women With Early Endometrial Cancer [NCT03241914]Phase 2/Phase 364 participants (Actual)Interventional2017-07-04Completed
Phase II Study of Everolimus Beyond Progression in Postmenopausal Women With Advanced, Hormone Receptor Positive Breast Cancer [NCT02269670]Phase 23 participants (Actual)Interventional2014-11-25Terminated(stopped due to Slow to accrual)
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

Trial Outcomes

TrialOutcome
NCT00483327 (3) [back to overview]Number of Women Who Became Pregnant
NCT00483327 (3) [back to overview]Best Pathologic Responses
NCT00483327 (3) [back to overview]Toxicity and Tolerability
NCT00575029 (2) [back to overview]Number of Participants With Adrenal Insufficiency
NCT00575029 (2) [back to overview]Time Required for Recovery From Adrenal Suppression to Normal Adrenal Function
NCT00637572 (11) [back to overview]Change From Baseline in Impedance
NCT00637572 (11) [back to overview]Change From Baseline in Body Fat Mass
NCT00637572 (11) [back to overview]Change in Tricep Skinfold
NCT00637572 (11) [back to overview]Change From Baseline in Lean Mass
NCT00637572 (11) [back to overview]Change in Hip Circumference
NCT00637572 (11) [back to overview]Change in Mid-arm Circumference
NCT00637572 (11) [back to overview]Change in Total Energy
NCT00637572 (11) [back to overview]Change in Waist Circumference
NCT00637572 (11) [back to overview]Appetite at Baseline (Day 3) and Week 12
NCT00637572 (11) [back to overview]Change in Body Weight
NCT00637572 (11) [back to overview]Quality of Life (QoL) Via Bristol-Myers Anorexia/Cachexia Recovery Instrument (BACRI) at Baseline (Day 3) and Week 12 (BACRI)
NCT00729586 (5) [back to overview]Percentage of Participants With a Confirmed Objective Tumor Response Using RECIST Version 1.0
NCT00729586 (5) [back to overview]Duration of Overall Survival (OS)
NCT00729586 (5) [back to overview]Duration of Progression-free Survival (PFS)
NCT00729586 (5) [back to overview]Incidence of Adverse Effects (Grade 3 or Higher) as Assessed by Common Terminology Criteria for Adverse Events Version 3.0
NCT00729586 (5) [back to overview]Number of Participants and Their Levels of Expression of the Candidate Markers
NCT00910091 (12) [back to overview]Percentage of Participants >65 Years of Age With No Change or Deterioration, Improvement of <10%, or Improvement of ≥10% on the EuroQoL Score
NCT00910091 (12) [back to overview]Percentage of Participants With Adverse Event (AE)
NCT00910091 (12) [back to overview]Tolerability of BN83495 Based on Dose Interruptions and Reason for Interruptions
NCT00910091 (12) [back to overview]Overall Survival (OS)
NCT00910091 (12) [back to overview]Duration of Response (DR) in Responders
NCT00910091 (12) [back to overview]Percentage of Participants With Clinical Benefit [Including Completed Response (CR), Partial Response (PR), and Stable Disease (SD)] ≥12 Weeks
NCT00910091 (12) [back to overview]Percentage of Participants With First Documentation of Objective Tumour Progression From Randomisation
NCT00910091 (12) [back to overview]Percentage of Participants With Overall Response (OR) Including CR and PR
NCT00910091 (12) [back to overview]Percentage of Women With Advanced or Recurrent Endometrial Cancer Who Have Neither Progressed Nor Died
NCT00910091 (12) [back to overview]Progression Free Survival (PFS): Time From Randomisation Until Objective Tumour Progression or Death From Any Cause
NCT00910091 (12) [back to overview]Tolerability of BN83495 Based on Cumulative Dose Administered
NCT00910091 (12) [back to overview]Tolerability of BN83495 Based on Length of Exposure
NCT01206478 (2) [back to overview]% Calories Taken Orally
NCT01206478 (2) [back to overview]Change in Non-communicating Children's Pain Checklist - Revised (NCCPC-R) Scores
NCT01237327 (5) [back to overview]Overall Survival
NCT01237327 (5) [back to overview]Time to Treatment Failure (TTF)
NCT01237327 (5) [back to overview]Time to Tumor Progression (TTP)
NCT01237327 (5) [back to overview]Duration of Response (DR)
NCT01237327 (5) [back to overview]Objective Response Rate (ORR)
NCT01968317 (4) [back to overview]Recurrence Rate
NCT01968317 (4) [back to overview]Cumulative CR Rates Within 16 Weeks
NCT01968317 (4) [back to overview]Cumulative CR Rates Within 32 Weeks
NCT01968317 (4) [back to overview]Pregnancy Rate
NCT02595723 (1) [back to overview]Rey Auditory Verbal Learning Test (RAVLT)
NCT03077698 (3) [back to overview]Progression-free Survival (PFS)
NCT03077698 (3) [back to overview]Overall Survival (OS)
NCT03077698 (3) [back to overview]Duration of Stable Disease

Number of Women Who Became Pregnant

(NCT00483327)
Timeframe: up to 3 years after the treatment for each patient

Interventionparticipants (Number)
Megestrol Acetate3

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Best Pathologic Responses

Patients are evaluated every 12 weeks while on treatment. The response is evaluated by endometrial biopsy or dilation and curettage (D&C)/hysteroscopy. Complete response (CR) is defined as endometrial sampling is read as normal or proliferative endometrium. Partial response (PR) is defined as the biopsy sample has changed on the endometrial evaluation scale by at least one level towards normal. Stable disease (SD) is defined as no change in pathology between the index and follow-up sample. Progressive disease (PD) is defined the follow-up sample has changed towards neoplasia on the endometrial evaluation scale by at least one level or imaging is concerning for myometrial invasion or extrauterine disease such that conservative management is no longer medically appropriate. (NCT00483327)
Timeframe: up to 24 months

Interventionparticipants (Number)
Pathologic CRUnconfirmed CRPRSDPD
Megestrol Acetate174612

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Toxicity and Tolerability

Patients with adverse events (AEs) which were possibly, probably, or definitely related to the treatment. AEs were evaluated according to Common Terminology Criteria for Adverse Events (CTCAE) 3. (NCT00483327)
Timeframe: up to 36 months

,
Interventionparticipants (Number)
Weight gainMood alterationsHeadacheThromboembolic eventCarpal tunnel syndromeWeaknessVaginal SpottingVaginal PainNauseaInsomniaFatigueAbdominal PainConstipationIncreased AppetiteDepressionBloating
Grade 1 or 29450116164623434
Grade 30021000000000000

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Number of Participants With Adrenal Insufficiency

Number of participants with adrenal insufficiency after treatment with megestrol acetate assessed by ACTH stimulated cortisol levels less than normal (21 ug/dl) measured weekly for 8 weeks or when adrenal insufficiency is clinically encountered (NCT00575029)
Timeframe: stimulated acth stimulated cortisol levels weekly for 8 weeks or until adrenal insufficiency is encountered

Interventionparticipants (Number)
Megestrol Acetate7

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Time Required for Recovery From Adrenal Suppression to Normal Adrenal Function

the number of weeks required for participants to recover from adrenal suppression as assessed by a normal ACTH stimulation test (cortisol level >21 mcg/dl) (NCT00575029)
Timeframe: weekly for up to 6 weeks

Interventionweeks (Number)
participant 1participant 2participant 3participant 4participant 5participant 6participant 7
Megestrol Acetate6222222

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Change From Baseline in Impedance

Electrical impedance is a method for body composition assessment. The procedure involves sending a small current through the body and measuring the resistance in ohm. High resistance is associated with smaller amounts of fat-free mass. Smaller resistance is associated with large amounts of fat-free mass. (NCT00637572)
Timeframe: Baseline (Day 1) to Week 12

Interventionohms (Mean)
Megestrol Acetate Oral Suspension Nanocrystal Dispersion21.6
Megestrol Acetate Oral Suspension Micronized Formulation12.2

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Change From Baseline in Body Fat Mass

(NCT00637572)
Timeframe: Baseline (Day 1) to Week 12

Interventionkg (Mean)
Megestrol Acetate Oral Suspension Nanocrystal Dispersion3.2
Megestrol Acetate Oral Suspension Micronized Formulation2.2

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Change in Tricep Skinfold

(NCT00637572)
Timeframe: Baseline (Day 1) to Week 12

Interventioncm (Mean)
Megestrol Acetate Oral Suspension Nanocrystal Dispersion1.0
Megestrol Acetate Oral Suspension Micronized Formulation1.5

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Change From Baseline in Lean Mass

(NCT00637572)
Timeframe: Baseline (Day 1) to Week 12

Interventionkg (Mean)
Megestrol Acetate Oral Suspension Nanocrystal Dispersion2.1
Megestrol Acetate Oral Suspension Micronized Formulation1.3

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Change in Hip Circumference

(NCT00637572)
Timeframe: Baseline (Day 1) to Week 12

Interventioncm (Mean)
Megestrol Acetate Oral Suspension Nanocrystal Dispersion2.5
Megestrol Acetate Oral Suspension Micronized Formulation1.8

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Change in Mid-arm Circumference

(NCT00637572)
Timeframe: Baseline (Day 1) to Week 12

Interventioncm (Mean)
Megestrol Acetate Oral Suspension Nanocrystal Dispersion-0.6
Megestrol Acetate Oral Suspension Micronized Formulation1.1

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Change in Total Energy

Food intake was quantified by the 24-hour recall food diary (NCT00637572)
Timeframe: Baseline (Day 1) to Week 12

Interventionkcal (Mean)
Megestrol Acetate Oral Suspension Nanocrystal Dispersion215.9
Megestrol Acetate Oral Suspension Micronized Formulation150.6

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Change in Waist Circumference

(NCT00637572)
Timeframe: Baseline (Day 1) to Week 12

Interventioncm (Mean)
Megestrol Acetate Oral Suspension Nanocrystal Dispersion7.1
Megestrol Acetate Oral Suspension Micronized Formulation5.4

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Appetite at Baseline (Day 3) and Week 12

"Appetite was assessed via visual analogue scale (VAS) as part of the Bristol-Myers Anorexia/Cachexia Recovery Instrument (BACRI) (Question 5 only). The question was To what extent has your appetite changed since the start of treatment? The response was captured on a VAS scale in cm with a range from 0 ( much worse) to 10 (much better)." (NCT00637572)
Timeframe: Baseline (Day 3) to Week 12

,
Interventioncm (Mean)
Baseline Day 3Week 12
Megestrol Acetate Oral Suspension Micronized Formulation5.88.0
Megestrol Acetate Oral Suspension Nanocrystal Dispersion6.18.4

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Change in Body Weight

Weight gain in adult HIV positive subjects who have weight loss with AIDS related wasting within the first 12 weeks of treatment (NCT00637572)
Timeframe: Baseline (Day 1) to Week 12

,
Interventionkg (Mean)
OverallMaleFemale
Megestrol Acetate Oral Suspension Micronized Formulation3.53.53.5
Megestrol Acetate Oral Suspension Nanocrystal Dispersion5.47.02.3

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Quality of Life (QoL) Via Bristol-Myers Anorexia/Cachexia Recovery Instrument (BACRI) at Baseline (Day 3) and Week 12 (BACRI)

The BACRI instrument is used to measure the benefit of weight gain treatment provided to anorexic patients on health related quality of life aspects. The scale is composed of 9 subscales (0 to 10 [worse to better]). The response was captured on a VAS scale in cm. The total BACRI score is the sum with a minimum score 0=worse and maximum score 90=better. These subscales are: change in weight impacting health; concern about weight; appearance change; change feeling of appearance; change in appetite; enjoy eating; overall feeling; benefit of treatment; and quality of life. (NCT00637572)
Timeframe: Baseline (Day 3) to Week 12

,
Interventioncm (Mean)
Baseline (Day 3)Week 12
Megestrol Acetate Oral Suspension Micronized Formulation50.165.6
Megestrol Acetate Oral Suspension Nanocrystal Dispersion52.367.6

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Percentage of Participants With a Confirmed Objective Tumor Response Using RECIST Version 1.0

RECIST 1.0 defines complete response as the disappearance of all target lesions and non-target lesions and no evidence of new lesions documented by two disease assessments at least 4 weeks apart. Partial response is defined as at least a 30% decrease in the sum of longest dimensions (LD) of all target measurable lesions taking as reference the baseline sum of LD. There can be no unequivocal progression of non-target lesions and no new lesions. Documentation by two disease assessments at least 4 weeks apart is required. In the case where the ONLY target lesion is a solitary pelvic mass measured by physical exam, which is not radiographically measurable, a 50% decrease in the LD is required. These patients will have their response classified according to the definitions stated above. Complete and partial responses are included in the objective tumor response rate. (NCT00729586)
Timeframe: Radiologic tumor evaluations at baseline and every 6 weeks for the first 24 weeks; then repeated every 12 weeks until disease progression. Repeat after treatment discontinuation if patient was taken off study for reasons other than progression.

Interventionpercentage of participants (Number)
Arm 1: Temsirolimus22
Arm 2: Megestrol Acetate+Tamoxifen+ Temsirolimus14.3

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Duration of Overall Survival (OS)

Overall survival is defined as the duration of time from study entry to time of death or the date of last contact. (NCT00729586)
Timeframe: Every 6 weeks during treatment, then every 3 months for one year.

Interventionmonths (Median)
Arm 1: Temsirolimus13.3
Arm 2: Megestrol Acetate+Tamoxifen+ Temsirolimus9.6

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Duration of Progression-free Survival (PFS)

Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions assessed radiographically and 50% increase if the only target lesion is a solitary pelvic mass measured by physical exam, or unequivocal progression of a non-target lesion, or the appearance of new lesions. (NCT00729586)
Timeframe: Radiologic tumor evaluations at baseline and every six weeks for the first 24 weeks and then repeated every 12 weeks until disease progression. Repeat after treatment discontinuation if patient was taken off study for reasons other than progression.

Interventionmonths (Median)
Arm 1: Temsirolimus5.6
Arm 2: Megestrol Acetate+Tamoxifen+ Temsirolimus4.2

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Incidence of Adverse Effects (Grade 3 or Higher) as Assessed by Common Terminology Criteria for Adverse Events Version 3.0

Number of participants with a maximum grade of 3 or higher during the treatment period. (NCT00729586)
Timeframe: Assessed every 6 weeks while on treatment, 30 days after the last cycle of treatment.

InterventionParticipants (Count of Participants)
Arm 1: Temsirolimus29
Arm 2: Megestrol Acetate+Tamoxifen+ Temsirolimus15

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Number of Participants and Their Levels of Expression of the Candidate Markers

The levels of expression of the candidate markers measured prior to study treatment are tabulated. The expressions being tabulated include immunohistochemical expression of hormone receptors. The hormone receptors are estrogen receptor positive, progesterone receptors-A, progesterone receptor-B, PAKT Positive and PTEN Positive. The associations between the immunohistochemical expression of these biomarkers and between these biomarkers and treatment, outcome or clinical characteristics are reported for future investigation. (NCT00729586)
Timeframe: Baseline

Interventionparticipants (Number)
Estrogen Receptor PositiveProgesterone Receptor PositiveProgesterone Receptor B PositivePAKT PositivePTEN Positive
Receptor Analysis2030351130

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Percentage of Participants >65 Years of Age With No Change or Deterioration, Improvement of <10%, or Improvement of ≥10% on the EuroQoL Score

EuroQoL (Quality of Life)-5 Dimensions (EQ-5D) is a participant answered questionnaire scoring 5 dimensions: Mobility, self-care, usual activities, pain/discomfort and anxiety/depression. EQ-5D total score ranges from 0 (worst health state) to 1 (perfect health state) and 1 reflects the best outcome. (NCT00910091)
Timeframe: Up to week 32

,
InterventionPercentage of participants (Number)
No Change or Deterioration at week 2No Change or Deterioration at week 4No Change or Deterioration at week 8No Change or Deterioration at week 16No Change or Deterioration at week 24No Change or Deterioration at week 32Improvement of <10% at week 2Improvement of <10% at week 4Improvement of <10% at week 8Improvement of <10% at week 16Improvement of <10% at week 24Improvement of <10% at week 32Improvement of ≥10% at week 2Improvement of ≥10% at week 4Improvement of ≥10% at week 8Improvement of ≥10% at week 16Improvement of ≥10% at week 24Improvement of ≥10% at week 32
Arm A: BN83495 40 mg54.254.225.025.016.716.70.04.24.20.00.08.320.816.716.712.512.50.0
Arm B: MA 160 mg50.061.150.050.033.322.25.65.65.60.05.65.65.616.716.75.65.65.6

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Percentage of Participants With Adverse Event (AE)

Grade 1: Mild, Grade 2: Moderate, Grade 3: Severe, Grade 4: Life threatening/disabling and Grade 5: Death (NCT00910091)
Timeframe: Up to Day 28 follow-up

,
InterventionPercentage of subjects (Number)
Any AEsAny Treatment Emergent AEs (TEAEs)Intensity of TEAEs - Grade 5Intensity of TEAEs - Grade 4Intensity of TEAEs - Grade 3Intensity of TEAEs - Grade 2Intensity of TEAEs - Grade 1Intensity of TEAEs - MissingCausality of TEAEs - RelatedCausality of TEAEs - Not relatedTEAEs Leading to WithdrawalTEAEs Leading to DeathSerious Adverse Events (SAEs)
Arm A: BN83495 40 mg88.988.92.85.622.263.980.65.655.677.88.32.825.0
Arm B: MA 160 mg82.982.92.90.025.745.774.30.037.177.12.92.917.1

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Tolerability of BN83495 Based on Dose Interruptions and Reason for Interruptions

Percentage of participants who had dose interruptions and reason for interruptions as AE, study treatment forgotten, and other reasons. (NCT00910091)
Timeframe: Up to 2 years

,
InterventionPercentage of participants (Number)
Dose InterruptionsReason for Interruptions (AE)Reason for Interruptions (Treatment forgotten)Reason for Interruptions (Other)
Arm A: BN83495 40 mg27.816.70.013.9
Arm B: MA 160 mg34.58.68.620.0

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Overall Survival (OS)

OS is defined as the time from the date of enrollment to the date of death due to any cause. (NCT00910091)
Timeframe: At 2 years

InterventionWeeks (Median)
Arm A: BN83495 40 mg63.43
Arm B: MA 160 mgNA

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Duration of Response (DR) in Responders

DR is defined as period from the time that measurement criteria are first met for CR or PR until first date of documented Progressive Disease (PD) or death. DR was assessed in participants with a best overall response of CR or PR. (NCT00910091)
Timeframe: At 2 years

InterventionWeeks (Median)
Arm A: BN83495 40 mgNA
Arm B: MA 160 mg105.14

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Percentage of Participants With Clinical Benefit [Including Completed Response (CR), Partial Response (PR), and Stable Disease (SD)] ≥12 Weeks

"CR: Disappearance of all known disease & no new sites / disease related symptoms confirmed at least 12 weeks after initial documentation. Disappearance of all non-target lesions. Normalization of tumor marker level confirmed at least 12 weeks after initial documentation.~PR: Minimum 30% decrease in sum of the longest diameters of target lesions, taking as a reference the baseline sum of the longest diameters confirmed at least 12 weeks after initial documentation. PR is also recorded when all measurable disease has completely disappeared, but a non-measurable component (i.e., ascites) is still present but not progressing. As well as persistence of one or more non-target lesion(s) and/or maintenance of tumor marker level above normal limits.~RECIST defines SD for target lesions as neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease, no occurrence of progression disease for non-target lesions, and no new lesions." (NCT00910091)
Timeframe: Up to 2 years

InterventionPercentage of Participants (Mean)
Arm A: BN83495 40 mg13
Arm B: MA 160 mg19

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Percentage of Participants With First Documentation of Objective Tumour Progression From Randomisation

(NCT00910091)
Timeframe: Up to 2 years

InterventionPercentage of Participants (Mean)
Arm A: BN83495 40 mg30
Arm B: MA 160 mg24

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Percentage of Participants With Overall Response (OR) Including CR and PR

(NCT00910091)
Timeframe: Up to 2 years

InterventionPercentage of Participants (Mean)
Arm A: BN83495 40 mg3
Arm B: MA 160 mg11

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Percentage of Women With Advanced or Recurrent Endometrial Cancer Who Have Neither Progressed Nor Died

Subject continuation in the study and Response Evaluation Criteria in Solid Tumours (RECIST) assessment has been based on investigator assessment and not on central review. The 6 month timepoint is defined as the treatment start date +183 days (26 weeks). (NCT00910091)
Timeframe: Up to 6 months

InterventionPercentage of subjects (Number)
Arm A: BN83495 40 mg36.1
Arm B: MA 160 mg54.1

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Progression Free Survival (PFS): Time From Randomisation Until Objective Tumour Progression or Death From Any Cause

(NCT00910091)
Timeframe: Up to 2 years

InterventionWeeks (Median)
Arm A: BN83495 40 mg16.14
Arm B: MA 160 mg40.14

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Tolerability of BN83495 Based on Cumulative Dose Administered

Cumulative dose is the actual total dose administered. (NCT00910091)
Timeframe: Up to 2 years

Interventionmg (Mean)
Arm A: BN83495 40 mg9452.22
Arm B: MA 160 mg60703.03

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Tolerability of BN83495 Based on Length of Exposure

Length of exposure includes interruptions. (NCT00910091)
Timeframe: Up to 2 years

InterventionWeek (Mean)
Arm A: BN83495 40 mg34.94
Arm B: MA 160 mg55.20

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% Calories Taken Orally

Percent Kilocalories (kcal) Obtained Orally. This measure was obtained using the 24 hour food recall, a standardized five-pass method developed by the US Department of Agriculture for use in national dietary surveillance. This measure has been widely used in several large trials and data suggest it is the most valid and reliable method of dietary assessment for children (20). The data were collected at week 0, week 10, and week 24 using standardized probes by highly trained research staff, and parents were presented with paper food models and measuring devices prior to interviews to reference during the recall. Recalls were analyzed with the Nutritional Data System for Research, version 2005; University of Minnesota, Minneapolis, MN. (NCT01206478)
Timeframe: baseline, 24 weeks

Interventionchange in percent kcal obtained orally (Mean)
Amitriptyline, Megestrol68.62
Placebo, Megestrol76.89

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Change in Non-communicating Children's Pain Checklist - Revised (NCCPC-R) Scores

Non-communicating Children's Pain Checklist - Revised (NCCPC-R) used to measure outcome. The NCCPC-R is a 30 item measure intended to assess pain in children who are unable to speak because of cognitive or physical impairments. There are 7 sub-scales including vocal, social, facial, activity, body/limbs, physiological, and eating/sleeping. Each question has a potential score of 0 to 3. Scores are totaled for each sub-scale. Sub-scale scores are then added together for the Total Score. Total Scores can range from 0 to 90. The higher the score, the higher level of pain indicated by the child. This measure was completed by parents at week 0, week 10, and week 24. (NCT01206478)
Timeframe: baseline, 24 weeks

Interventionunits on a scale (Mean)
Amitriptyline, Megestrol-2.5
Placebo, Megestrol-6.86

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Overall Survival

Overall survival in months measured from date of starting treatment in core study to date of death for any reason. (NCT01237327)
Timeframe: Every 12 weeks up to 6 years

Interventionmonths (Median)
Exemestane29.2
Megestrol Acetate16.3

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Time to Treatment Failure (TTF)

TTF = time between first day of study treatment and date of diagnosis of progression, withdrawal from study treatment for any reason, administration of other antitumor treatment, or death from any cause, whichever was the earliest event. (NCT01237327)
Timeframe: Every 12 weeks up to 6 years

Interventionmonths (Median)
Exemestane6.0
Megestrol Acetate3.7

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Time to Tumor Progression (TTP)

TTP = time between first day of study treatment and date of documented disease progression, or date of tumor-related death in the absence of previously documented progressive disease (PD). PD defined as a 25% or greater increase in size of 1 or more lesions compared to smallest previous assessment, or appearance of new lesion, or unequivocal worsening of bone lesions, or progression of nonevaluable lesions. (NCT01237327)
Timeframe: Every 12 weeks up to 6 years

Interventionmonths (Median)
Exemestane6.0
Megestrol Acetate3.7

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Duration of Response (DR)

Duration of objective response (complete response [CR] or partial response [PR]) calculated from date objective response was first documented to date of progressive disease. For subjects proceeding from PR to CR, the onset of PR was taken as the onset of objective response. (NCT01237327)
Timeframe: Every 12 weeks up to 6 years

Interventionmonths (Median)
Exemestane12.9
Megestrol Acetate35.4

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Objective Response Rate (ORR)

Percentage of participants achieving an objective response (OR) defined as complete response (CR) or partial response (PR) out of the total number of participants randomized in each treatment group (NCT01237327)
Timeframe: Every 12 weeks up to 6 years

Interventionpercentage of participants (Number)
Exemestane23.3
Megestrol Acetate12.2

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Recurrence Rate

All patients were followed up till February 2019. Statistics of patients who didn't accept hysterectomy and were not lost to follow up were analyzed. (NCT01968317)
Timeframe: through study completion, a median time of 33 months

InterventionParticipants (Count of Participants)
Megestrol Acetate and Metformin7
Megestrol Acetate6

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Cumulative CR Rates Within 16 Weeks

"The primary objective was to determine whether metformin plus MA would be associated with a higher CR rate at 3 months of treatment compared with MA alone. However, for patients who eventually underwent the first and second hysteroscopies for endometrium evaluation within 16 weeks of the treatment, the cumulative CR rates within 16 weeks (16w-CR) were analysed as first end point instead of the CR rate at 3 months.~Complete response was defined as the reversion of AEH/EEC to proliferative or secretory endometrium in pathology." (NCT01968317)
Timeframe: 16 weeks after initial treatment

InterventionParticipants (Count of Participants)
Megestrol Acetate and Metformin23
Megestrol Acetate12

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Cumulative CR Rates Within 32 Weeks

One of the secondary objectives was between-group comparisons of the cumulative CR rate at 6 months treatment. However, for patients who eventually underwent the second hysteroscopies for endometrium evaluation within 32 weeks of the treatment, the cumulative CR rates within 32 weeks (32w-CR rates) were analysed as secondary end point instead of the CR rate at 6 months. (NCT01968317)
Timeframe: 32 weeks after initial treatment

InterventionParticipants (Count of Participants)
Megestrol Acetate and Metformin52
Megestrol Acetate45

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Pregnancy Rate

All patients were followed up till February 2019. The pregnancy rate was calculated only in women who planned for parenthood immediately after achieving CR. (NCT01968317)
Timeframe: through study completion, a median time of 33 months

InterventionParticipants (Count of Participants)
Megestrol Acetate and Metformin19
Megestrol Acetate15

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Rey Auditory Verbal Learning Test (RAVLT)

Rey Auditory Verbal Learning Test (RAVLT) is a test of verbal learning and declarative memory. During the test, 15 nouns that are read aloud for 5 consecutive trials. Each trial is followed by a free recall test (participant is asked to recall the words that were just read to them). The sum of correctly recalled words across 5 trials is called the total raw score. The raw scores on the total recall (number of words correct across trials 1-5) are converted to standardized T-scores (Mean=50; SD=10; range 20-100) based on participant age and gender. The scores below are presented as T-scores, with higher scores indicative of better performance. (NCT02595723)
Timeframe: 4 days after intervention administration

InterventionT-scores (Mean)
Phenytoin, Then Megestrol51.89
Placebo, Then Megestrol45.90
Placebo, Then Placebo48.37

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Progression-free Survival (PFS)

Progressive Disease was assessed using RECIST Guideline (version 1.1) whereas at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression. Progression-free Survival (PFS) was defined as the duration of time from initiation of Treatment Period 2 (Day 0) until disease progression or death from any cause, whichever occurs first. For the purpose of analysis of PFS, subjects with an unknown response were censored. (NCT03077698)
Timeframe: 24 months

Interventiondays (Number)
001-15-01001-30-01001-39-05001-45-02001-48-01001-01-03001-39-07001-39-08001-43-01001-45-01001-47-03
Sodium Cridanimod & Progestin Therapy1685485851663132886014473

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Overall Survival (OS)

Once disease progression was documented in Treatment Period 2, subjects returned for the Safety Follow-up Visit four (4) weeks following the last treatment and continued to be followed for an additional 12-month period for overall survival. Overall Survival (OS) was defined as the duration of time from initiation of Treatment Period 2 (Day 0) until the subject's death from any cause. For the purpose of analysis of OS, if a subject is alive at the date of last contact the subject was censored at that date of contact. (NCT03077698)
Timeframe: 12 months

Interventiondays (Number)
001-15-01001-30-01001-39-05001-45-02001-48-01001-01-03001-39-07001-39-08001-43-01001-45-01001-47-03
Sodium Cridanimod & Progestin Therapy529411473541490773239465386438

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Duration of Stable Disease

Stable Disease (SD) was assessed using RECIST Guideline (version 1.1) whereas neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. Duration of Stable Disease was defined as the duration of time from initiation of Treatment Period 2 (Day 0) until the criteria for disease progression were first met. For the purpose of analysis of Duration of SD, subjects who died before documented progressive disease were censored. (NCT03077698)
Timeframe: 24 months

Interventiondays (Number)
001-15-01001-48-01001-45-01
Sodium Cridanimod & Progestin Therapy168166144

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