Delving into the Latest Updates on Megestrol Acetate with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

17-Acetoxy-6-methylpregna-4,6-diene-3,20-dione, 17-Hydroxy-6-methylpregna-4,6-diene-3,20-dione 17-acetate, 17alpha-Acetoxy-6-dehydro-6-methylprogesterone

+ [36]

Target

PR

Mechanism

PR agonists(Progesterone receptor agonists)

Therapeutic Areas

Immune System DiseasesInfectious DiseasesUrogenital Diseases

Active Indication

Acquired Immunodeficiency Syndrome

Inactive Indication

AnorexiaCachexiaDementia+ [4]

Originator Organization

Bristol Myers Squibb Co.

Active Organization

Endo Operations Ltd.

Inactive Organization

Par Pharmaceutical, Inc.Endo Pharmaceuticals, Inc.

Bristol Myers Squibb Co.

+ [2]

Drug Highest PhaseApproved

First Approval Date

US (18 Aug 1971),

Acquired Immunodeficiency Syndrome

RegulationOrphan Drug (US)

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Structure

Molecular FormulaC24H32O4

InChIKeyRQZAXGRLVPAYTJ-GQFGMJRRSA-N

CAS Registry595-33-5

A total of 221 patients were included; 58 % of patients (91/157) were stage I, 12 % (19/157) stage II, 13 % (20/157) stage III, and 17 % (27/157) stage IV. Surgery was the primary treatment for 98 % (213/218). Only 79 patients received hormonal adjuvant therapy, 58 % (46/79) Megace, 24 % (19/79) Letrozole, and 18 % (14/79) received other hormonal therapy. There was no significant difference in RFS (p = 0.159) and OS (p = 0.167) between patients receiving Megace versus Letrozole as adjuvant therapy. At first recurrence, patients given Megace had a similar RFS to those on Letrozole (p = 0.302), but a better OS (27 vs 10 months, p = 0.018). Negative status of estrogen, smooth muscle actin, and desmin were associated with lower RFS (p = 0.039, p = 0.002, and p = 0.015, respectively) and OS (p = 0.008, p = 0.012, and p = 0.013, respectively). Lymphovascular invasion was associated with lower RFS (p = 0.033), and negative status of progesterone was associated with lower OS (p = 0.003).

CONCLUSION:

There was no difference in oncologic outcomes between Megace and Letrozole in patients who received adjuvant therapy for LG-ESS. Megace may have potential survival advantage in recurrent disease. Further study is warranted to determine the most effective agents and their sequence in the treatment of LG-ESS.

20 Nov 2024·Nan fang yi ke da xue xue bao = Journal of Southern Medical University

[Megestrol acetate plus metformin for fertility-sparing treatment of atypical endometrial hyperplasia and early-stage endometrial adenocarcinoma: a prospective study].

Article

Author: Bai, Jing ; Chu, Danxia ; Lai, Tianjiao ; Yan, Shuping ; Guo, Ruixia ; Wang, Yuanyuan ; Qin, Haixia

OBJECTIVE:

To evaluate the efficacy of medroxyprogesterone acetate (MA) plus metformin as the primary fertility-sparing treatment for atypical endometrial hyperplasia (AEH) and early-stage grade 1 endometrial adenocarcinoma (G1 EAC) and the recurrence rate after treatment.

METHODS:

Sixty patients (aged 20-42 years) with AEH and/or grade 1 EAC limited to the endometrium were enrolled prospectively and randomized into two groups (n=30) to receive oral MA treatment at the daily dose of 160 mg (control) or MA plus oral metformin (850 mg, twice a day) for at least 6 months. The treatment could extend to 12 months until a complete response (CR) was achieved, and follow-up hysteroscopy and curettage were performed every 3 months. For all the patients who achieved CR, endometrial expressions of IGFBP-rP1, p-Akt and p-AMPK were detected immunohistochemically.

RESULTS:

A total of 58 patients completed the treatment. After 9 months of treatment, 23 (76.7%) patients in the combined treatment group and 20 (71.4%) in the control group achieved CR; two patients in the control group achieved CR after converting to the combined treatment. The recurrence rate did not differ significantly between the control group and combined treatment group (30.0% vs 22.7%, P>0.05). Ten (35.7%) patients in the control group experienced significant weight gain of 5.7±6.1 kg, while none of the patients receiving the combined treatment exhibited significant body weight changes. Compared with the control group, the patients receiving the combined treatment showed enhanced endometrial expressions of IGFBP-rP1 and p-AMPK with lowered p-Akt expression.

CONCLUSION:

Metformin combined with MA may provide an effective option for fertility-sparing treatment of AEH and grade 1 stage IA EAC, and the clinical benefits of metformin for controlling MA-induced weight gain and promoting endometrial expressions of IGFBP-rP1 and p-AMPK while inhibiting p-Akt expression warrants further study.

01 Nov 2024·Immunity Inflammation and Disease

Identification of Vesicle‐Mediated Transport‐Related Genes for Predicting Prognosis, Immunotherapy Response, and Drug Screening in Cervical Cancer

Article

Author: Lv, Hongqing ; Zhang, Lin ; Lou, Shuai

ABSTRACT:

Background:

Cervical cancer is one of the most common malignancies among women. Vesicle‐mediated transport mechanisms significantly influence tumor cell behavior through intercellular material exchange. However, prognostic significance in CC patients remains underexplored.

Research Design and Methods:

We identified differentially expressed vesicle‐mediated transport‐related genes from TCGA and GeneCards datasets through differential expression analysis. We constructed a prognostic model using Cox regression and LASSO regression, categorized patients into high‐ and low‐risk groups, and validated the model in the GEO data set. A nomogram integrating clinical features and risk scores demonstrated the model's independent prognostic capability. We analyzed tumor immune cell infiltration, immune checkpoints, and predicted immunotherapy responses in the high‐ and low‐risk groups. Finally, we screened potential drugs for targeting CC and conducted drug‐sensitivity analysis.

Results:

We successfully established a 10‐gene prognostic model based on VMTRGs. The low‐risk group exhibited favorable prognosis, significant immune cell infiltration, and promising immunotherapy response, whereas the high‐risk group showed higher sensitivity to chemotherapeutic agents such as Docetaxel and Paclitaxel. Potential drugs identified for targeting CC patients included Megestrol acetate, Lenvatinib, Adavosertib, and Barasertib.

Conclusions:

The VMTRG‐based prognostic model demonstrates reliable clinical prognostic value and enhances understanding of vesicle‐mediated transport mechanisms in CC.

100 Deals associated with Megestrol Acetate

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External Link

KEGG	Wiki	ATC	Drug Bank
D00952	Megestrol Acetate	G03DB02 G03AC05 L02AB01	DB00351

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Acquired Immunodeficiency Syndrome	US	Bristol Myers Squibb Co.	18 Aug 1971

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Dementia	Phase 3	ES	Rottapharm Sl	01 Jun 2007
Neoplasms	Phase 3	US	Par Pharmaceutical, Inc.	01 Jun 2006
Anorexia	Phase 3	US	Bristol Myers Squibb Co.	31 Aug 2001
Cachexia	Phase 3	US	Bristol Myers Squibb Co.	31 Aug 2001
Pulmonary Disease, Chronic Obstructive	Phase 2	ES	Rottapharm Sl	01 Oct 2006
HIV Wasting Syndrome	Phase 2	US	Endo Pharmaceuticals, Inc.	01 Dec 2004
HIV Wasting Syndrome	Phase 2	IN	Endo Pharmaceuticals, Inc.	01 Dec 2004
HIV Wasting Syndrome	Phase 2	ZA	Endo Pharmaceuticals, Inc.	01 Dec 2004
Malnutrition	Phase 2	US	Bristol Myers Squibb Co.	31 Aug 2001

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT05492487 (not provided, Pubmed \| J Assist Reprod Genet)	Phase 2	Endometrioid intraepithelial neoplasia	-	Megestrol Acetate	beryalhmlk(xnrwuvargg) = grwxbegopy gjvuscjzsf (rlrdjskpak ) View more	Positive	31 Aug 2024
				Levonorgestrel-Intrauterine System	beryalhmlk(xnrwuvargg) = grtparabos gjvuscjzsf (rlrdjskpak ) View more
ASCO2024	Not Applicable	Neoplasms	-	Megestrol Acetate	olikbqoysd(frsrmziqsg) = fmslqlldvd fsqplluzps (coisfdaknc ) View more	-	24 May 2024
NCT03024580 (MEGA trial, ESMO_BC2023)	Phase 2	Estrogen receptor positive breast cancer ER+ \| HER2-	20	Megestrol-Acetate (MA)	kywogtlbax(bvqsiqtpir) = uyibunpnrm uefkdagaxu (cinbzpnxvz ) View more	Negative	12 May 2023
				Another Hormone Therapy (AHT)	kywogtlbax(bvqsiqtpir) = gbcycfmnxs uefkdagaxu (cinbzpnxvz ) View more
ESGO2022	Not Applicable	Endometrial Carcinoma estrogen receptor \| progesterone receptors	83	Tamoxifen-progestin combination therapy	bhcgdnowva(msbbossgpc) = nhzpashqsf fgbhsbpzrk (lzdvbdapof )	Positive	20 Oct 2022
				Progestin-only therapy	bhcgdnowva(msbbossgpc) = kiphjtdeml fgbhsbpzrk (lzdvbdapof )
NCT01968317 (CTgov)	Phase 2	Endometrioid intraepithelial neoplasia \| uterus adenocarcinoma	150	Megestrol acetat+metformin (Megestrol Acetate and Metformin)	upzzxpogvc(kxkmydqkpj) = bdzaxhzqwu alluwwlnam (ywmmkrxlch, vkvrqvsrmx - ejbwxcmnyy) View more	-	13 Sep 2021
				megestrol acetate (Megestrol Acetate)	upzzxpogvc(kxkmydqkpj) = soajcxybgb alluwwlnam (ywmmkrxlch, tfmupixhjh - owcacnvsop) View more
NCT00503581 (CTgov)	Phase 2	Uterine Corpus Cancer \| Endometrioid intraepithelial neoplasia \| Endometrial Hyperplasia ... View more	9	Quality-of-Life Assessment+megestrol acetate (Regimen 1 (Megestrol Acetate, Surgery))	tbdhgitxfl(ngsejdncsm) = wccuuhfabj nwhnobfvpj (dawptztfhj, jnojynssgx - elvwxaqzzg) View more	-	14 Oct 2020
				Quality-of-Life Assessment+megestrol acetate (Regimen 2 (Megestrol Acetate, Surgery))	tbdhgitxfl(ngsejdncsm) = mnsabysoph nwhnobfvpj (dawptztfhj, pjshkcnsjj - aghuwjntaf) View more
IGCS2019	Not Applicable	Endometrioid intraepithelial neoplasia \| Endometrial Carcinoma	150	Megestrol acetate (MA)	jlujcnavcp(aabbezkxoo) = gdrrvscayx pzvznmkcgm (qjbssnwlbz ) View more	Positive	18 Sep 2019
				Megestrol acetate (MA) plus metformin	jlujcnavcp(aabbezkxoo) = jdcrbmmuqk pzvznmkcgm (qjbssnwlbz ) View more
NCT02595723 (CTgov)	Phase 4	Cognitive Dysfunction \| Amnesia, Anterograde	21	Megestrol 800 mg liquid+Phenytoin 200 mg capsule (Phenytoin, Then Megestrol)	mvrccipjya(rtwucnumxu) = dnoyhgnfna ywyntdnsjq (lwbzhpiivt, lbpyvkzydc - ndfrxjuaov) View more	-	09 Sep 2019
				Phenytoin-matched Placebo capsule+Megestrol 800 mg liquid (Placebo, Then Megestrol)	mvrccipjya(rtwucnumxu) = wiyfsmxcvq ywyntdnsjq (lwbzhpiivt, nitblcdufr - mhommbtegw) View more
NCT01206478 (CTgov)	Phase 2	-	21	Megestrol+Amitriptyline (Amitriptyline, Megestrol)	dmtihrthnh(jhrkmnwynd) = numatkgntb tnsbludbee (rapauxeogx, rppsdrsazy - huexwprrhy) View more	-	15 Aug 2016
				Placebo+Megestrol (Placebo, Megestrol)	dmtihrthnh(jhrkmnwynd) = ubamenovir tnsbludbee (rapauxeogx, fottkcecfv - wabahlajmc) View more
NCT00637806 (CTgov)	Phase 3	Neoplasms \| Cachexia \| Anorexia	4	MA-CS (DB MA-CS 550 mg/Day)	rlnxmhvedf(fnimwrcyje) = jvpfbzctdv hvghlzpsyn (nirnivlkwk, fihiwzaufn - fpaxaryklp) View more	-	02 May 2016
				DB MA-CS (DB MA-CS 300 mg/Day)	rlnxmhvedf(fnimwrcyje) = osdkmxiaxp hvghlzpsyn (nirnivlkwk, yephhyjagj - wrazsbmfve) View more