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Cancer Medicine Aug 2023The objective of this study is to determine primary survival endpoints in women with recurrent and metastatic endometrial carcinoma (RMEC) treated with progestins.
PURPOSE
The objective of this study is to determine primary survival endpoints in women with recurrent and metastatic endometrial carcinoma (RMEC) treated with progestins.
METHODS
A retrospective chart review was conducted at The Ottawa Hospital using electronic medical records. Inclusion criteria were a diagnosis of RMEC between 2000 and 2019, endometrioid histology, and ≥one line of progestin treatment. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method.
RESULTS
Of 2342 cases reviewed, 74 met inclusion criteria. Sixty-six (88.0%) patients received megestrol acetate and 9 (12.0%) received a progestin alternative. The distribution of tumors by grade was: 1: 25 (33.3%), 2: 30 (40.0%), and 3: 20 (26.7%). The PFS and OS for the entire study sample was 14.3 months (95% CI 6.2-17.9) and 23.3 months (14.8-36.8), respectively. The PFS for patients with Grade 1-2 RMEC was 15.7 months (8.0, 19.5), compared to 5.0 months (3.0, 23.0) with Grade 3 disease. The OS for patients with Grade 1-2 versus Grade 3, was 25.9 months (15.3, 40.3) versus 12.5 months (5.7, 35.9), respectively. Thirty-four (45.9%) and 40 (54.1%) patients were treated with 0 and ≥1 line of chemotherapy. The PFS for chemotherapy-naïve patients was 17.9 months (14.3, 27.0), versus 6.2 months (3.9, 14.8) following ≥1 line of treatment. The OS was 29.1 months (17.9, 61.1) for chemotherapy-naïve patients versus 23.0 months (10.5, 37.6) for patients previously exposed.
CONCLUSIONS
This real-world data on RMEC suggests there is a role for progestins in select subgroups of women. The PFS for chemotherapy-naïve patients was 17.9 months (14.3, 27.0), versus 6.2 months (3.9, 14.8) following ≥1 line of treatment. The OS was 29.1 months (17.9, 61.1) for chemotherapy-OS was 29.1 months (17.9, 61.1) for chemotherapy-naïve patients versus 23.0 months (10.5, 37.6) for patients previously exposed.
Topics: Humans; Female; Progestins; Retrospective Studies; Neoplasm Recurrence, Local; Endometrial Neoplasms; Megestrol Acetate; Antineoplastic Combined Chemotherapy Protocols
PubMed: 37417528
DOI: 10.1002/cam4.6276 -
Semergen Mar 2024
Review
Topics: Humans; Megestrol Acetate; Adrenal Insufficiency
PubMed: 38043387
DOI: 10.1016/j.semerg.2023.102084 -
Translational and Clinical Pharmacology Mar 2024Megestrol is commonly used to address appetite loss, cachexia, and significant weight loss in cancer or acquired immune deficiency syndrome patients. This study aimed to...
UNLABELLED
Megestrol is commonly used to address appetite loss, cachexia, and significant weight loss in cancer or acquired immune deficiency syndrome patients. This study aimed to assess the pharmacokinetics and determine the bioequivalence of two orally administered megestrol acetate suspensions (625 mg/5 mL) in healthy Korean male subjects. A randomized, open-label, single-dose crossover study was conducted involving fifty-four healthy male subjects who were randomized into two sequence groups. Each subject received either a test or reference drug formulation of 625 mg/5 mL megestrol acetate with a two-week washout period between treatments. Plasma samples were collected before and up to 120 hours after administration, and their plasma drug concentrations were analyzed using validated liquid chromatography-mass spectrometry/mass spectrometry. The pharmacokinetic parameters were calculated, and bioequivalence was confirmed if the 90% confidence intervals of the geometric mean ratios were within the specified bounds of 80.00% to 125.00%. In total, fifty-two subjects completed the study, contributing to the pharmacokinetic analysis. The 90% confidence intervals for the geometric mean ratios of the test formulation compared to the reference formulation were 93.85% to 108.90% for maximum plasma concentration and 91.60% to 101.78% for area under the concentration-time curve from the point of administration to last time point of blood sampling. Throughout the study, no serious or unexpected adverse events were observed. The pharmacokinetic profiles of both formulations of megestrol acetate (625 mg) were comparable and well tolerated in healthy Korean male adult subjects. The test formulation met regulatory criteria for bioequivalence.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT06147908.
PubMed: 38586120
DOI: 10.12793/tcp.2024.32.e6 -
Zhonghua Yi Xue Za Zhi Mar 2024To assess the long-term efficacy of metformin in megestrol acetate (MA)-based fertility-sparing treatment for patients with endometrial atypical hyperplasia (EAH) and... (Randomized Controlled Trial)
Randomized Controlled Trial
[The long-term efficacy of metformin in megestrol acetate-based fertility-sparing treatment for patients with endometrial atypical hyperplasia and endometrioid endometrial cancer].
To assess the long-term efficacy of metformin in megestrol acetate (MA)-based fertility-sparing treatment for patients with endometrial atypical hyperplasia (EAH) and endometrioid endometrial cancer (EEC). The randomized controlled trail study was conducted from October 2013 to October 2017 in the Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China. Patients with EAH or EEC were firstly stratified according to pathology, and randomized to receive MA (160 mg orally, daily) plus metformin (500 mg orally, three times a day) or MA (160 mg orally, daily). Baseline data between two groups of patients were compared. Estimates of time to complete remission (CR) and recurrence-free survival (RFS) were calculated using the Kaplan-Meier method. Cox proportional-hazards regression model was used to estimate hazard ratios () of related factors for recurrence-free survival. Quantitative data were represented by (, ). A total of 150 patients were included, and 76 patients were allocated to receive MA plus metformin with the age of 32.5 (28.0, 36.0), while 74 patients received MA alone with the age of 32.0 (28.0, 36.0). By the end of follow-up period, 96.7% (=145) of patients achieved complete remission, with a median follow-up time of 57.7 (26.7, 70.5) months. The median CR time for the MA plus metformin group and the MA alone group were 6.3 (3.5, 8.3) months and 6.8 (4.0, 9.3) months, respectively (=0.193), with 2-year cumulative CR rate of 98.6% and 98.5%, respectively (=0.879). The median time of RFS was 28.1 (12.5, 57.3) months for the MA plus metformin group and 33.3 (14.1, 62.5) months for the MA alone group (=0.213), with a cumulative RFS rate of 61.9% and 65.8%, respectively (=0.560). In the subgroup of non-obese (body mass index<28 kg/m) patients with EAH, the median RFS times were 25.7 (7.6, 60.3) months and 47.3 (17.5, 64.8) months for the MA plus metformin group and the MA alone group, respectively (=0.033), with a cumulative RFS rate of 57.5% and 80.6%, respectively (=0.029). According to Cox proportional hazards regression analysis, undergoing assisted reproductive treatment (=2.358, 95%: 1.069-5.204, =0.034) was identified as an independent risk factor for recurrence-free survival after complete remission of endometrial lesions. The long-term follow-up outcome indicates that there is no significant difference in CR time and RFS time between MA plus metformin therapy and MA alone therapy for patients with EAH or EEC.
Topics: Pregnancy; Female; Humans; Megestrol Acetate; Metformin; Hyperplasia; Endometrial Neoplasms; Fertility Preservation; Treatment Outcome; China; Endometrial Hyperplasia; Retrospective Studies
PubMed: 38462352
DOI: 10.3760/cma.j.cn112137-20231016-00768 -
BMJ Case Reports May 2024Endometrial carcinoma (EC) is the sixth most common cancer in females. Most ECs are detected in stage 1 and have a 5-year survival rate of more than 90%. Recurrence...
Endometrial carcinoma (EC) is the sixth most common cancer in females. Most ECs are detected in stage 1 and have a 5-year survival rate of more than 90%. Recurrence rates are highest within 5 years after treatment and are exceptionally rare after 10 years. Here, we describe a woman in her late 70s with endometrial cancer who was treated in 2008 and was diagnosed with a relapse in her left lung in 2023. Due to her advanced age and comorbidities, she was deemed inoperable. However, she received sequential chemotherapy and radiotherapy with a good partial response. She has now been started on hormonal therapy with an alternate megestrol and tamoxifen regime. There is a lack of follow-up imaging guidelines to detect late relapse, a dilemma in preferred treatment sequencing at relapse and an enigma in selecting chemotherapy or hormonal therapy.
Topics: Humans; Female; Endometrial Neoplasms; Lung Neoplasms; Neoplasm Recurrence, Local; Aged; Tamoxifen
PubMed: 38782427
DOI: 10.1136/bcr-2023-259008 -
The European Journal of Contraception &... Feb 2024To evaluate whether the thromboembolic risk and contraceptive effectiveness of NOMAC-E2 observed in the PRO-E2 study can be extended to each participating country, as...
PURPOSE
To evaluate whether the thromboembolic risk and contraceptive effectiveness of NOMAC-E2 observed in the PRO-E2 study can be extended to each participating country, as lifestyle, cardiovascular risk factors and prescribing habits may differ geographically. This analysis was performed on the PRO-E2 Italian subpopulation, where smoking habit and women over 35 years were more prevalent compared with the overall study population.
MATERIALS AND METHODS
Data from NOMAC-E2 or levonorgestrel-containing COCs (COC) new users were descriptively analysed. Incidence rates of thrombosis (events/10,000 women-years [WY]) and the Pearl Index (pregnancies/100 WY) were calculated.
RESULTS
Overall, 11,179 NOMAC-E2 and 8,504 COC users were followed up to 2 years (34,869 WY). The NOMAC-E2 cohort included more women over 35 vs. COC (37.7% vs. 31.8%; = 0.001). A comparable low risk of combined deep venous thrombosis of lower extremities (DVT) and pulmonary embolism (PE) was observed in NOMAC-E2 (1.7/10,000 WY; 95% CI: 0.21-6.2) and COC users (6.6/10,000 WY; 95% CI: 2.4-14.4). Similar results were obtained by considering all thromboembolic events (VTE). Unintended pregnancies did not differ between NOMAC-E2 (0.12/100 WY; 95% CI: 0.06-0.21) and COC (0.15/100 WY; 95% CI: 0.08-0.26) cohorts.
CONCLUSION
Despite the higher age and tobacco use, findings from the Italian subpopulation were broadly consistent with overall PRO-E2 results, confirming a similar low thromboembolic risk and high contraceptive effectiveness of NOMAC-E2 and COC.
SHORT CONDENSATION
This subgroup analysis of the PRO-E2 study provides comprehensive epidemiological data on the use of combined oral contraceptives in a large Italian cohort, with a higher prevalence of women over 35 years and smokers. The study confirms the low thromboembolic risk and high contraceptive effectiveness of NOMAC-E2 pill.
Topics: Pregnancy; Female; Humans; Male; Ethinyl Estradiol; Estradiol; Megestrol; Contraceptive Effectiveness; Venous Thromboembolism; Contraceptives, Oral, Combined; Italy
PubMed: 38085301
DOI: 10.1080/13625187.2023.2284085 -
Japanese Journal of Clinical Oncology May 2024Cancer-related anorexia-cachexia comprises one of the most common syndromes of advanced cancer patients. The management of cancer-related anorexia-cachexia is a great... (Randomized Controlled Trial)
Randomized Controlled Trial Comparative Study
OBJECTIVE
Cancer-related anorexia-cachexia comprises one of the most common syndromes of advanced cancer patients. The management of cancer-related anorexia-cachexia is a great challenge in clinical practice. There are no definite practice guidelines yet for the prevention and treatment of cancer-related anorexia-cachexia. This study is considered to find out whether there is any role of mirtazapine in the improvement of anorexia in cancer patients.
METHODS
A total of 80 cancer-anorexia patients were enrolled. Patients in the trial arm received the standard chemotherapy medication plus one tablet of mirtazapine 15 mg daily at night orally for 8 weeks starting from the day of an initial assessment. The control arm received the standard chemotherapy medication plus one tablet of megestrol acetate 160 mg daily orally for 8 weeks starting from the day of an initial assessment. Each patient was assessed by validated versions of Functional Assessment of Anorexia/Cachexia Therapy Anorexia/Cachexia Sub Scale v 4 questionnaires.
RESULTS
After 4 and 8 weeks each patient was evaluated again using the Functional Assessment of Anorexia/Cachexia Therapy Anorexia/Cachexia Sub Scale tool. The quality of life of each patient was assessed by European Organization for Research and Treatment QLQ-C30 v 3.0. After 4 to 8 weeks of treatment, the Functional Assessment of Anorexia/Cachexia Therapy Anorexia/Cachexia Sub Scale score in cancer anorexia patients in the mirtazapine improved anorexia significantly. However, the improvement after 4 to 8 weeks was not statistically significant when it was compared with the megestrol acetate (P > 0.05).
CONCLUSIONS
Therefore, the findings of this study reveal that mirtazapine might be a potential alternative to megestrol acetate, as it has shown potential efficacy as like as megestrol acetate.
Topics: Humans; Mirtazapine; Anorexia; Megestrol Acetate; Male; Middle Aged; Neoplasms; Female; Cachexia; Double-Blind Method; Aged; Quality of Life; Adult; Mianserin; Appetite Stimulants
PubMed: 38323684
DOI: 10.1093/jjco/hyae009 -
Supportive Care in Cancer : Official... Mar 2024Megestrol acetate (MA) is used to manage anorexia and cachexia in patients with advanced cancer. This study investigated the prescription patterns of MA in patients with...
OBJECTIVE
Megestrol acetate (MA) is used to manage anorexia and cachexia in patients with advanced cancer. This study investigated the prescription patterns of MA in patients with metastatic gastric cancer, as well as evaluated its impact on survival outcomes and the incidence of venous thromboembolism (VTE).
METHODS
A Health Insurance Review and Assessment (HIRA) service database was used to investigate differences in baseline characteristics, survival, and the incidence of VTE according to MA prescription patterns (i.e., prescription vs. no prescription) in patients diagnosed with metastatic gastric cancer from July 2014 to December 2015.
RESULTS
A total of 1938 patients were included in this study. In total, 65% of the patients were prescribed MA. Older age, treatment in tertiary hospitals, and palliative chemotherapy were statistically significant predictive factors for MA prescription. Continuous prescription of MA was observed in 37% of patients. There was no statistically significant difference in survival between the MA and non-MA prescription groups on multivariate analysis. Among the 1427 patients included in the analysis for VTE incidence, 4.3% and 2.9% were diagnosed with VTE during the follow-up period in the MA and non-MA prescription groups, respectively. However, there was no statistically significant difference in VTE diagnosis between the groups on multivariate analysis.
CONCLUSION
MA is commonly prescribed for metastatic gastric cancer, especially in elderly patients and those undergoing palliative chemotherapy, without significantly affecting survival or VTE risk.
Topics: Humans; Aged; Megestrol Acetate; Stomach Neoplasms; Venous Thromboembolism; Cachexia; Insurance, Health; Transcription Factors; Cell Cycle Proteins; Histone Chaperones
PubMed: 38530439
DOI: 10.1007/s00520-024-08430-5 -
Frontiers in Oncology 2024The objective of this network meta-analysis is to systematically compare the efficacy of diverse progestin-based combination regimens in treating patients diagnosed with...
OBJECTIVES
The objective of this network meta-analysis is to systematically compare the efficacy of diverse progestin-based combination regimens in treating patients diagnosed with endometrial cancer or atypical endometrial hyperplasia. The primary goal is to discern the optimal combination treatment regimen through a comprehensive examination of their respective effectiveness.
METHODS
We systematically searched four prominent databases: PubMed, Web of Science, Embase, and Cochrane Central Register of Controlled Trials, for randomized controlled trials addressing the efficacy of progestins or progestin combinations in the treatment of patients with endometrial cancer or atypical endometrial hyperplasia. The search spanned from the inception of these databases to December 2023. Key outcome indicators encompassed survival indices, criteria for assessing efficacy, as well as pregnancy and relapse rate. This study was registered in PROSPERO (CRD42024496311).
RESULTS
From the 1,558 articles initially retrieved, we included 27 studies involving a total of 5,323 subjects in our analysis. The results of the network meta-analysis revealed that the mTOR inhibitor+megestrol acetate (MA)+tamoxifen regimen secured the top rank in maintaining stable disease (SD) (SUCRA=73.4%) and extending progression-free survival (PFS) (SUCRA=72.4%). Additionally, the progestin combined with tamoxifen regimen claimed the leading position in enhancing the partial response (PR) (SUCRA=75.2%) and prolonging overall survival (OS) (SUCRA=80%). The LNG-IUS-based dual progestin regimen emerged as the frontrunner in improving the complete response (CR) (SUCRA=98.7%), objective response rate (ORR) (SUCRA=99.1%), pregnancy rate (SUCRA=83.7%), and mitigating progression (SUCRA=8.0%) and relapse rate (SUCRA=47.4%). In terms of safety, The LNG-IUS-based dual progestin regimen had the lowest likelihood of adverse events (SUCRA=4.2%), while the mTOR inhibitor regimen (SUCRA=89.2%) and mTOR inbitor+MA+tamoxifen regimen (SUCRA=88.4%) had the highest likelihood of adverse events.
CONCLUSIONS
Patients diagnosed with endometrial cancer or atypical endometrial hyperplasia exhibited the most favorable prognosis when undergoing progestin combination therapy that included tamoxifen, mTOR inhibitor, or LNG-IUS. Notably, among these options, the LNG-IUS-based dual progestin regimen emerged as particularly promising for potential application.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO, identifier CRD42024496311.
PubMed: 38764577
DOI: 10.3389/fonc.2024.1391546 -
Cureus Jan 2024In this case report, we discuss a patient who experienced spontaneous regression of multiple intracranial meningiomas that were treated conservatively for 5 years after...
In this case report, we discuss a patient who experienced spontaneous regression of multiple intracranial meningiomas that were treated conservatively for 5 years after cessation of megestrol acetate, an exogenous progestin. In addition, we discuss the previous literature describing the relationship between exogenous progesterone medications and meningioma growth. This case, along with others reported, implies that cessation of progesterone therapy, when feasible, may alter the natural history of meningioma growth and thus impact treatment decisions.
PubMed: 38371126
DOI: 10.7759/cureus.52479