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European Journal of Obstetrics,... Jul 2023
Topics: Female; Humans; Meningioma; Endometriosis; Megestrol; Norpregnadienes; Meningeal Neoplasms
PubMed: 37183159
DOI: 10.1016/j.ejogrb.2023.05.002 -
Gynecologic Oncology Jul 2023To compare the effects of levonorgestrel-intrauterine system (LNG-IUS) with or without oral megestrol acetate (MA) versus MA alone on fertility-preserving treatment in... (Randomized Controlled Trial)
Randomized Controlled Trial
Comparison of the effect of levonorgestrel-intrauterine system with or without oral megestrol acetate on fertility-preserving treatment in patients with atypical endometrial hyperplasia: A prospective, open-label, randomized controlled phase II study.
OBJECTIVE
To compare the effects of levonorgestrel-intrauterine system (LNG-IUS) with or without oral megestrol acetate (MA) versus MA alone on fertility-preserving treatment in patients with atypical endometrial hyperplasia (AEH).
METHODS
This was a single-center phase II study with an open-label, randomized, controlled trial conducted between July 2017 and June 2020 at the Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China. A total of 180 patients (18-45 years) with primary AEH were randomly assigned (1:1:1) to the MA (N = 60), LNG-IUS (N = 60), or MA + LNG-IUS (N = 60) groups, in which the patients received MA (160 mg orally daily), LNG-IUS, or MA + LNG-IUS (MA 160 mg orally daily plus LNG-IUS), respectively. The primary endpoint was complete response (CR) rate at 16 weeks of treatment. The secondary endpoints were CR rate at 32 weeks of treatment, adverse events, and recurrence and pregnancy rates. All analyses were conducted in a modified intention to treat (ITT) population who underwent randomization and in whom treatment was initiated.
RESULTS
The Kaplan-Meier estimate of 16-week CR rates (with 95% confidence interval) were 19.2% (9.0-29.4%) in the MA group, 35.0% (22.8-47.2%) in the LNG-IUS group, and 29.4% (17.2-41.6%) in the MA + LNG-IUS groups. Side effects such as weight gain, increased nocturnal urine, night sweat, insomnia and edema face seemed to occur less frequently in LNG-IUS group compared with MA group. No difference was found among groups regarding second endpoints.
CONCLUSIONS
LNG-IUS or LNG-IUS plus MA did not show significant therapeutic benefit compared with MA alone. Further studies including sufficient sample-size are needed to validate these findings due to the underpowered design of this trial.
FUNDING
This study was supported by the National Key Research and Development Program of China (Grant No 2019YFC1005200 and 2019YFC1005204), Shanghai Medical Centre of Key Programs for Female Reproductive Diseases (Grant No. 2017ZZ010616), Shanghai sailing program (Grant No. 19YF1404200), and Shen Kang clinical project (SHDC22021219). Trial registrationClinicalTrials.govNCT03241888. https://www.
CLINICALTRIALS
gov/ct2/show/NCT03241888?term=NCT03241888&draw=2&rank=1.
Topics: Pregnancy; Humans; Female; Levonorgestrel; Endometrial Hyperplasia; Megestrol Acetate; Prospective Studies; China; Fertility; Intrauterine Devices, Medicated
PubMed: 37182434
DOI: 10.1016/j.ygyno.2023.05.001 -
Gynecologic Oncology Jul 2023To evaluate oncologic and pregnancy outcomes of fertility-sparing treatment (FST) using progestin in patients with stage I grade 2 endometrioid endometrial cancer (EC)...
Fertility-sparing hormonal treatment in patients with stage I endometrial cancer of grade 2 without myometrial invasion and grade 1-2 with superficial myometrial invasion: Gynecologic Oncology Research Investigators coLLaborAtion study (GORILLA-2001).
OBJECTIVES
To evaluate oncologic and pregnancy outcomes of fertility-sparing treatment (FST) using progestin in patients with stage I grade 2 endometrioid endometrial cancer (EC) without myometrial invasion (MI) or grade 1-2 with superficial MI.
METHODS
Multicenter data of patients with stage I grade 2 EC without MI or grade 1-2 EC with superficial MI, who received FST between 2005 and 2021, were analyzed. Cox regression analysis identified independent factors for progressive disease (PD) during the FST.
RESULTS
Altogether, 54 patients received FST [medroxyprogesterone acetate (500-1000 mg) in 44, megestrol acetate (40-800 mg) in 10] with concurrent levonorgestrel-releasing intrauterine devices use in 31. With median time to achieve a complete response (CR) of 10 (3-24) months, 39 patients (72.2%) achieved CR. Of the 15 patients who attempted to conceive after achieving CR, 7 (46.7%) became pregnant (2 abortions, 5 live births). During a median FST duration of 6 (3-12) months, nine patients (16.6%) were diagnosed with PD. Fifteen (38.5%) experienced recurrence with a median recurrence-free survival of 23 (3-101) months. In the multivariable analysis, tumor size before FST ≥2 cm (HR 5.456, 95% CI 1.34 to 22.14; p = 0.018) was significantly associated with a high PD rate during FST.
CONCLUSION
The overall response rate to FST was promising, however, the PD rate was significant during the first 12 months of FST. Therefore, performing thorough endometrial biopsy and imaging studies is essential to strictly evaluate the extent of the disease every 3 months from FST initiation.
Topics: Female; Humans; Pregnancy; Antineoplastic Agents, Hormonal; Endometrial Neoplasms; Fertility Preservation; Proportional Hazards Models; Retrospective Studies; Treatment Outcome; Progestins; Disease Progression; Neoplasm Staging; Adolescent; Young Adult; Adult; Biopsy
PubMed: 37172410
DOI: 10.1016/j.ygyno.2023.04.027 -
International Journal of Molecular... Apr 2023Adrenocortical cancer (ACC) is a rare malignancy with a dismal prognosis. The treatment includes mitotane and EDP chemotherapy (etoposide, doxorubicin, and cisplatin)....
BACKGROUND
Adrenocortical cancer (ACC) is a rare malignancy with a dismal prognosis. The treatment includes mitotane and EDP chemotherapy (etoposide, doxorubicin, and cisplatin). However, new therapeutic approaches for advanced ACC are needed, particularly targeting the metastatic process. Here, we deepen the role of progesterone as a new potential drug for ACC, in line with its antitumoral effect in other cancers.
METHODS
NCI-H295R, MUC-1, and TVBF-7 cell lines were used and xenografted in zebrafish embryos. Migration and invasion were studied using transwell assays, and MMP2 activity was studied using zymography. Apoptosis and cell cycle were analyzed by flow cytometry.
RESULTS
Progesterone significantly reduced xenograft tumor area and metastases formation in embryos injected with metastatic lines, MUC-1 and TVBF-7. These results were confirmed in vitro, where the reduction of invasion was mediated, at least in part, by the decrease in MMP2 levels. Progesterone exerted a long-lasting effect in metastatic cells. Progesterone caused apoptosis in NCI-H295R and MUC-1, inducing changes in the cell-cycle distribution, while autophagy was predominantly activated in TVBF-7 cells.
CONCLUSION
Our results give support to the role of progesterone in ACC. The involvement of its analog (megestrol acetate) in reducing ACC progression in ACC patients undergoing EDP-M therapy is now under investigation in the PESETA phase II clinical study.
Topics: Animals; Humans; Adrenocortical Carcinoma; Progesterone; Matrix Metalloproteinase 2; Zebrafish; Cell Line, Tumor; Adrenal Cortex Neoplasms
PubMed: 37047801
DOI: 10.3390/ijms24076829 -
Journal of Ovarian Research Mar 2023Successful pregnancy outcome in women with synchronous ovarian and endometrial cancers is very rare. We report successful pregnancy outcome in a young woman managed...
BACKGROUND
Successful pregnancy outcome in women with synchronous ovarian and endometrial cancers is very rare. We report successful pregnancy outcome in a young woman managed conservatively for synchronous endometrial and ovarian cancer.
CASE PRESENTATION
Thirty years old nulliparous lady presented following exploratory laparotomy, left salpingo-oophorectomy and hysteroscopic polypectomy for left adnexal mass. Histology revealed endometrioid carcinoma of left ovary and moderately differentiated adenocarcinoma in the resected polyp. She underwent staging laparotomy along with hysteroscopy which confirmed above findings without any evidence of further tumor spread. She was treated conservatively with high dose oral progestin (megestrol acetate, 160 mg) and leuprolide acetate 3.75 mg monthly injections for three months along with four cycles of carboplatin and paclitaxel based chemotherapy followed by monthly injection of leuprolide for further three months. After failure of spontaneous conception, she underwent ovulation induction for six cycles along with intrauterine insemination which failed. She underwent in vitro fertilization with donor egg followed by elective cesarean section at 37 weeks of gestation. She delivered a healthy baby of weight 2.7 kg. Intraoperatively 5 × 6 cm right ovarian cyst was found which drained chocolate coloured fluid on puncture and cystectomy was carried out. Histological examination revealed endometrioid cyst of right ovary. Uterus was spared as she wanted to preserve her fertility. She is being followed periodically and is normal nine months following delivery. She is on injection Depot medroxy progesterone acetate once every three months.
Topics: Humans; Pregnancy; Female; Adult; Ovary; Cesarean Section; Uterus; Endometrial Neoplasms; Fertilization in Vitro
PubMed: 36991430
DOI: 10.1186/s13048-023-01137-x -
Cancers Mar 2023Hormonal therapy has long been a treatment modality for recurrent endometrial cancer. It is appealing for patients with low-grade, slow-growing tumors or in patients for... (Review)
Review
Hormonal therapy has long been a treatment modality for recurrent endometrial cancer. It is appealing for patients with low-grade, slow-growing tumors or in patients for which other treatment types may be too toxic. Hormonal therapy is well tolerated and has response rates ranging from 9 to 33%. Hormonal treatment options take advantage of the estrogen-dependent molecular pathways in endometrial cancers. Current options for hormonal therapies include progesterone therapy (medroxyprogesterone acetate and megestrol acetate) as a single agent or in combination and agents that target the estrogen pathway. Aromatase inhibitors have had modest single-agent activity, but synergistic effects have been found when used in combination with targeted therapy including mTOR inhibitors and cyclin-dependent kinase 4/6 (CDK4/6) inhibitors. Molecular profiling of endometrial cancers has begun to help individualize treatments. This review will report on existing data and ongoing trials investigating novel hormonal therapy agents.
PubMed: 36980685
DOI: 10.3390/cancers15061799 -
Journal of Geriatric Oncology Apr 2023We aimed to estimate the nationwide prevalence of potentially inappropriate medication (PIM) use in patients with terminal cancer according to two deprescribing criteria...
INTRODUCTION
We aimed to estimate the nationwide prevalence of potentially inappropriate medication (PIM) use in patients with terminal cancer according to two deprescribing criteria for patients with a limited lifespan.
MATERIALS AND METHODS
This cross-sectional study evaluated the prevalence of PIM use using two datasets: national claims data and single-tertiary hospital data. In the claims data, patients with terminal cancer were defined as patients with cancers who died between April and June 2018 and were prescribed opioid analgesics or megestrol or were hospitalized for >90 days before the date of death. Using hospital data, patients who were enrolled in hospice care in 2019 were identified. PIM was defined according to the adjusted criteria from the Screening Tool for Older Persons' Prescriptions in frail adults with limited life expectancy (STOPPFrail) versions 1 and 2 and oncological palliative care deprescribing guidelines (OncPal) guidelines.
RESULTS
From the national claims data and single-tertiary hospital data, 1,558 patients and 1,243 patients were included in the analysis, respectively. In both datasets, over 60% of patients used five or more medications (claims data: 67.7%; hospital data: 63.9%), and approximately half of them used at least one PIM (claims data: 51.5%; hospital data: 43.2%). Lipid-lowering agents, acid suppressors, and hypoglycemics were common PIMs. Polypharmacy, age, and comorbid conditions, including diabetes, were associated with PIM use.
DISCUSSION
Approximately two-thirds and half of the patients with terminal cancer were exposed to polypharmacy and at least one PIM based on the STOPPFrail and OncPal criteria, respectively; therefore, deprescribing PIM in patients with terminal cancer is an urgent issue.
Topics: Humans; Aged; Aged, 80 and over; Potentially Inappropriate Medication List; Deprescriptions; Inappropriate Prescribing; Cross-Sectional Studies; Neoplasms; Tertiary Care Centers
PubMed: 36931198
DOI: 10.1016/j.jgo.2023.101472 -
Journal of Gynecologic Oncology Jul 2023To examine the effectiveness of progestin re-treatment for recurrent endometrial intraepithelial neoplasia (EIN), atypical endometrial hyperplasia (AH) and endometrial... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To examine the effectiveness of progestin re-treatment for recurrent endometrial intraepithelial neoplasia (EIN), atypical endometrial hyperplasia (AH) and endometrial cancer (EC) following initial fertility-sparing treatment.
METHODS
A comprehensive systematic review and meta-analysis were conducted by an Expert Panel of the Japan Society of Gynecologic Oncology Endometrial Cancer Committee. Multiple search engines, including PubMed/MEDLINE and the Cochrane Database, were searched in December 2021 using the keywords "Endometrial neoplasms," "Endometrial hyperplasia," "Endometrial intraepithelial neoplasia," "Fertility preservation," "Progestins," AND "Recurrence." Cases describing progestin re-treatment for recurrent EIN, AH and EC were compared with cases that underwent conventional hysterectomy. The primary outcomes were survival and disease recurrence, and the secondary outcome was pregnancy.
RESULTS
After screening 238 studies, 32 with results for recurrent treatment were identified. These studies included 365 patients (270 received progestin re-treatment and 95 underwent hysterectomy). Most progestin re-treatment involved medroxyprogesterone acetate or megestrol acetate (94.5%). Complete remission (CR) following progestin re-treatment was achieved in 219 (81.1%) cases, with 3-, 6- and 9-month cumulative CR rates of 22.8%, 51.7% and 82.6%, respectively. Progestin re-treatment was associated with higher risk of disease recurrence than conventional hysterectomy was (odds ratio [OR]=6.78; 95% confidence interval [CI]=1.99-23.10), and one patient (0.4%) died of disease. Fifty-one (14.0%) women became pregnant after recurrence, and progestin re-treatment demonstrated a possibility of pregnancy (OR=2.48; 95% CI=0.94-6.58).
CONCLUSION
This meta-analysis suggests that repeat progestin therapy is an effective option for women with recurrent EIN, AH and EC, who wish to retain their fertility.
Topics: Pregnancy; Female; Humans; Endometrial Hyperplasia; Progestins; Retrospective Studies; Neoplasm Recurrence, Local; Endometrial Neoplasms; Fertility Preservation; Treatment Outcome
PubMed: 36929578
DOI: 10.3802/jgo.2023.34.e49 -
Analytical Methods : Advancing Methods... Mar 2023Steroid hormones have been listed as priority pollutants in the environment, and their detection and pollution control deserve our extensive attention. In this study, a...
Steroid hormones have been listed as priority pollutants in the environment, and their detection and pollution control deserve our extensive attention. In this study, a modified silica gel adsorbent material was synthesized by benzoyl isothiocyanate reaction with hydroxyl groups on the silica gel surface. The modified silica gel was used as a solid phase extraction filler for the extraction of steroid hormones from water, which was further analyzed by the HPLC-MS/MS method. The FT-IR, TGA, XPS, and SEM analysis indicated that benzoyl isothiocyanate was successfully grafted on the surface of silica gel to form a bond with an isothioamide group and benzene ring as the tail chain. The modified silica gel synthesized at 40 °C showed excellent adsorption and recovery rates for three steroid hormones in water. Methanol at pH 9.0 was selected as the optimal eluent. The adsorption capacity of the modified silica gel for epiandrosterone, progesterone, and megestrol acetate was 6822 ng mg, 13 899 ng mg, and 14 301 ng mg, respectively. Under optimal conditions, the limit of detection (LOD) and limit of quantification (LOQ) for 3 steroid hormones by modified silica gel extraction with HPLC-MS/MS detection were 0.02-0.88 μg L and 0.06-2.22 μg L, respectively. The recovery rate of epiandrosterone, progesterone, and megestrol was between 53.7% and 82.9%, respectively. The modified silica gel has been successfully used to analyze steroid hormones in wastewater and surface water.
Topics: Silica Gel; Water; Tandem Mass Spectrometry; Progesterone; Spectroscopy, Fourier Transform Infrared; Androsterone; Steroids; Isothiocyanates
PubMed: 36807579
DOI: 10.1039/d2ay01852g -
Journal of Hazardous Materials Apr 2023The consumption of cytostatics, pharmaceuticals prescribed in chemotherapy, is increasing every year and worldwide, along with the incidence of cancer. The presence and...
The consumption of cytostatics, pharmaceuticals prescribed in chemotherapy, is increasing every year and worldwide, along with the incidence of cancer. The presence and the temporal evolution of cytostatics in wastewaters from a Portuguese hospital center was evaluated through a 9-month sampling campaign, comprising a total of one hundred and twenty-nine samples, collected from May 2019 to February 2020. Eleven cytostatics out of thirteen pharmaceuticals were studied, including flutamide, mycophenolate mofetil and mycophenolic acid, which have never been monitored before. Target analytes were extracted and quantified by solid-phase extraction coupled to liquid-chromatography-tandem mass spectrometry analysis; the method was fully validated. All pharmaceuticals were detected in at least one sample, bicalutamide being the one found with higher frequency (detected in all samples), followed by mycophenolic acid, which was also the compound detected at higher concentrations (up to 5340 ± 211 ng/L). Etoposide, classified as carcinogenic to humans, was detected in 60% of the samples at concentrations up to 142 ± 15 ng/L. The risk from exposure to cytostatics was estimated for aquatic organisms living in receiving bodies. Cyclophosphamide, doxorubicin, etoposide, flutamide, megestrol and mycophenolic acid are suspected to induce risk. Long-term and synergic effects should not be neglected, even for the cytostatics for which no risk was estimated.
Topics: Humans; Cytostatic Agents; Flutamide; Etoposide; Mycophenolic Acid; Water Pollutants, Chemical; Solid Phase Extraction; Environmental Monitoring; Pharmaceutical Preparations
PubMed: 36731320
DOI: 10.1016/j.jhazmat.2023.130883