Megestrol Research Articles

Oral administration of megestrol acetate can increase fat graft survival in a rat model

Insufficient and inconsistent survival is a significant shortcoming of fat grafts. Reportedly, megestrol acetate (MA) could induce proliferation, migration, and adipogenic differentiation of adipose-derived stem cells in vitro. Thus, we tested whether MA could promote fat graft survival in a rat model. Twenty-eight Sprague-Dawley rats (8 weeks old, male) were divided into two groups: experimental (MA group, n=14) and control (n=14). The inguinal fat pad (1g) was extracted en bloc and re-implanted under the scalp in both groups. MA (100mg/kg/day) was administered orally for 14 postoperative days in the experimental group. After 6 weeks, the volume and weight of the grafted fat were measured. Histologic examination with hematoxylin and eosin (HE) and real-time polymerase chain reaction (PCR) for vascular endothelial growth factor (VEGF), fibroblast growth factor 2 (FGF2), and CCAAT/enhancer-binding protein alpha (C/EBP-α) were performed. Perilipin staining was performed to check the viability of grafted fat. Graft fat volume was greater in the MA group, compared with that in the control (P=0.023). The MA group also had more viable cells, including more adipocytes, and less fibrosis or vacuoles than the control on HE and perilipin staining. MA upregulated the expression of FGF2 (P<0.001), VEGF (P=0.008), and C/EBP-α (P=0.002) at the second postoperative week. MA increased survival of grafted fat in an animal model. Increased vascularization and adipogenesis were related to these results. Further human clinical trials are necessary to evaluate adjunctive oral administration of MA after fat grafting to promote graft survival.

Hysteroscopic Curettage Followed by Megestrol Acetate Plus Metformin as a Fertility-Sparing Treatment for Women with Atypical Endometrial Hyperplasia or Well-Differentiated Endometrioid Endometrial Carcinoma.

Background:In reproductive-aged women, the incidence of atypical endometrial hyperplasia (AEH) or endometrioid endometrial carcinoma (EEC) is rising globally. The study aimed to investigate the effectiveness of hysteroscopic curettage followed by megestrol acetate (MA) plus metformin as conservative treatment in AEH and early EEC.Methods:We retrospectively studied AEH and stage IA, grade 1 EEC patients treated with hysteroscopic curettage followed by MA (160 mg/d) plus metformin (1500 mg/d) from January 2010 to December 2020 at Fudan University Shanghai Cancer Center. Treatment outcomes were assessed by complete response (CR) rate, recurrence rate, and pregnancy outcomes. Univariate and multivariate analyses were performed via the logistic regression model.Results:The study included 79 patients, 31 (39.2%) with AEH and 48 (60.8%) with EEC. The medians of age (years) and follow-up time (months) were 30 and 39.5, respectively. Seventy-six patients (96.2%) finally achieved CR. The median time to CR was 3.6 (3.0-20.6) months. The CR rate after 3 months, 6 months, and 1 year was 55 (69.6%), 67 (84.8%), and 72 (91.1%), respectively. Recurrence occurred in 26 (34.2%) patients. Treatment duration ⩾9 months was associated with a lower recurrence rate after CR (P = .012). Fourteen (93.3%) of the 15 recurrent patients who received progestin re-treatment achieved CR again. Finally, 29 patients delivered live births.Conclusions:Hysteroscopy followed by MA plus metformin can achieve CR in short time and is overall safe. Consolidation treatment should be prolonged to decrease the recurrence rate, despite a shorter time to CR.

Clinical Features and Risk Factors of Adrenal Insufficiency in Patients With Cancer Admitted to the Hospitalist-Managed Medical Unit.

BackgroundThe symptoms of adrenal insufficiency (AI) overlap with the common effects of advanced cancer and chemotherapy. Considering that AI may negatively affect the overall prognosis of cancer patients if not diagnosed in a timely manner, we analyzed the incidence, risk factors, and predictive methods of AI in cancer patients.MethodsWe retrospectively analyzed the medical records of 184 adult patients with malignancy who underwent a rapid adrenocorticotrophic hormone stimulation test in the medical hospitalist units of a tertiary hospital. Their baseline characteristics and clinical features were evaluated, and the risk factors for AI were identified using logistic regression analysis.ResultsOf the study patients, 65 (35%) were diagnosed with AI, in whom general weakness (63%) was the most common symptom. Multivariate logistic regression showed that eosinophilia (adjusted odds ratio [aOR], 4.28; 95% confidence interval [CI], 1.10–16.63; P = 0.036), history of steroid use (aOR, 2.37; 95% CI, 1.10–5.15; P = 0.028), and history of megestrol acetate use (aOR, 2.71; 95% CI, 1.38–5.33; P = 0.004) were associated with AI. Baseline cortisol levels of 6.2 μg/dL and 12.85 μg/dL showed a specificity of 95.0% and 95.4% for AI diagnosis, respectively.ConclusionAI was found in about one-third of patients with cancer who showed general symptoms that may be easily masked by cancer or chemotherapy, suggesting that clinical suspicion of AI is important while treating cancer patients. History of corticosteroids or megestrol acetate were risk factors for AI and eosinophilia was a pre-test predictor of AI. Baseline cortisol level appears to be a useful adjunct marker for AI.

Management of psychiatric disorders in patients with cancer.

Management of psychiatric disorders in patients with cancer.

Prevalence and Risk Factors for Adrenal Insufficiency in Patients with Multiple Myeloma Receiving Long-Term Chemotherapy including Corticosteroids: A Retrospective Cohort Study.

Multiple myeloma (MM) is the second most common hematologic malignancy and requires long-term and high-dose corticosteroid-based chemotherapy. The aim of this study was to investigate the prevalence and clinical predictors of corticosteroid-associated adrenal insufficiency (AI) in patients with MM receiving long-term chemotherapy. This retrospective study included patients with MM who were administered corticosteroid-based chemotherapy and underwent a rapid adrenocorticotropic hormone (ACTH) stimulation test between 2005 and 2018. AI was determined by a peak cortisol value < 18 μg/dL after ACTH stimulation. Demographic, clinical, and laboratory parameters were evaluated, and the prevalence and clinical risk factors of AI were examined. Of 282 patients with MM who received corticosteroid-based chemotherapy, 142 patients (50.4%) were classified as having AI. There were no differences in age, sex, body mass index, comorbidities, and laboratory findings, including serum sodium levels between the AI and no-AI groups. In univariate analysis, the cumulative dose of corticosteroid (odds ratio (OR) = 0.99, 95% confidence interval (CI) 0.98–0.99; P = 0.020) and megestrol acetate use (OR = 2.63, 95% CI 1.48–4.67; P = 0.001) were associated with the occurrence of AI. Cumulative duration and cumulative dose per duration of corticosteroid use were not associated with the occurrence of AI. However, in the multivariate analysis, only megestrol acetate use was associated with an increased risk of AI (OR = 2.54, 95% CI 1.41–4.60; P = 0.002). Approximately 95.8% of patients with AI had suspicious symptoms or signs of AI. Although clinical symptoms and signs are usually nonspecific, symptomatic patients with MM receiving long-term corticosteroid therapy have sufficient potential for developing AI, particularly when receiving megestrol acetate. These findings can help alert clinicians to consider adrenal suppression following corticosteroid-based chemotherapy in patients with MM.

Effect of Combination of Traditional Chinese Medicine with Western Medicine on Endometrial Carcinoma and Its Influence on Ultrasound, MRI, Tumor Markers HE4 and CA125.

Objective To study the clinical efficacy of integrated traditional Chinese medicine (TCM) and Western medicine (WM) in treating endometrial cancer and the influence on ultrasound, magnetic resonance imaging (MRI), tumor markers, human epididymis protein 4 (HE4) and carbohydrate antigen 125 (CA125). Method A total of 152 cases of patients with endometrial carcinoma were randomly divided into two groups: the TCM + WM group and the WM group. The WM group was treated with megestrol acetate tablets, and the TCM + WM group was treated with Radix Astragali injection on the basis of the control group. The levels of inflammatory factors, HE4 and CA125 in serum, were detected using enzyme-linked immunosorbent assay (ELISA) or radioimmunoassay. The characteristics of ultrasound images and MRI images were observed and recorded. Toxicity, side effects, and the 3-year cumulative survival rate after treatment were assessed. Results After treatment, the levels of interleukin-4 (IL-4), tumor necrosis factor-alpha (TNF-α), and high-sensitivity C-reactive protein (hs-CRP) in both groups decreased, and the decrease in the TCM + WM group was more obvious than that in the WM group. There were statistically significant differences between the two groups in lesion shape, boundary, blood flow signal, lesion diameter, resistance index (RI), echo, intima thickness, and muscle layer infiltration from transvaginal ultrasound images after treatment. The diameter, echo, boundary, shape, composition, and enhancement degree of lesions between the two groups have a significant difference. Moreover, the levels of serum HE4 and CA125 in both groups decreased after treatment, and the decrease in the TCM + WM group was more obvious than that in the WM group. There were statistically significant differences between the two groups in the occurrence of myelosuppression, abnormal liver function, decreased platelet number, gastrointestinal reactions, leukopenia, and cardiotoxicity. After three years of follow-up, the cumulative survival rate of the TCM + WM group was 76.32%, and the cumulative survival rate of the WM group was 57.89%. Conclusion Radix Astragali injection combined with megestrol acetate tablets has obvious therapeutic effects against endometrial cancer. Through vaginal ultrasonography and MRI, it can significantly improve the size, shape, and blood flow signals of patients' lesions, reduce the level of serum inflammatory factors and tumor markers HE4 and CA125, reduce the incidence of toxic and side reactions, improve the patient's immunity, improve the patient's condition significantly, and prolong the survival time of patients.

Intravascular adenomyomatosis: a morphologic variant of intravenous leiomyomatosis associated with endometriosis and potential for misdiagnosis

Intravenous leiomyomatosis (IVL) is a quasi-malignant smooth muscle tumor involving lymphatic and venous spaces of the myometrium. Rare cases of IVL with admixed endometrial glands and stroma have been described, termed intravascular adenomyomatosis. We report four additional cases of intravascular adenomyomatosis and expand the clinicopathologic features of these rare tumors. Patients were 39-45 years old and presented with symptoms of dysmenorrhea, postmenopausal bleeding, or pelvic mass. All cases were associated with endometriosis. Three cases comprised intravascular bland smooth muscle tumors with plexiform features, and in some foci, the intravascular tumor contained endometrial type glands and stroma. In one case, there was extensive (>10) foci of intravascular adenomyomatosis without evidence of associated smooth muscle neoplasm but did have an endometrial polyp with adenomyomatous features. None of the cases had nuclear atypia, increased mitotic activity, or tumor cell necrosis. The endometrial stromal components were positive for CD10 and negative or weakly positive for desmin by immunohistochemistry. Two cases underwent molecular testing for JAZF1 and PHF1 rearrangements with negative results. Three patients had no evidence of disease at the time of the last follow-up, and one had persistent but stable disease 7 years after incomplete surgical removal and megestrol acetate treatment. Intravascular adenomyomatosis is a variant morphology rarely seen in IVL that lacks characteristic morphologic and molecular features of endometrial stromal sarcoma. Similar to IVL, prognosis is likely linked to completeness of surgical resection. In this study, we found that intravascular adenomyomatosis is frequently associated with endometriosis, a novel finding to add to the literature on this rare IVL variant.

Fertility-Sparing Approach in Women Affected by Stage I and Low-Grade Endometrial Carcinoma: An Updated Overview.

Endometrial cancer (EC) is a deleterious condition which strongly affects a woman’s quality of life. Although aggressive interventions should be considered to treat high-grade EC, a conservative approach should be taken into consideration for women wishing to conceive. In this scenario, we present an overview about the EC fertility-sparing approach state of art. Type I EC at low stage is the only histological type which can be addressed with a fertility-sparing approach. Moreover, no myometrium and/or adnexal invasion should be seen, and lymph-vascular space should not be involved. Regarding the pharmaceutical target, progestins, in particular medroxyprogesterone acetate (MPA) or megestrol acetate (MA), are the most employed agent in conservative treatment of early-stage EC. The metformin usage and hysteroscopic assessment is still under debate, despite promising results. Particularly strict and imperious attention should be given to the follow-up and psychological wellbeing of women, especially because of the double detrimental impairment: both EC and EC-related infertility consequences.

Primary High-grade Serous Carcinoma of the Fallopian Tube as an Incidental Intraoperative Finding: A Case Report

: Primary carcinoma of the fallopian tube is a rare, but fatal gynecologic cancer. The preoperative diagnosis of this carcinoma is challenging due to the absence of specific symptoms and signs, and in most patients, it is an intraoperative finding. A 55-year-old patient (G3Ab1P2) was referred to the urogynecology clinic of our hospital with the chief complaints of heavy, prolonged menstrual bleeding and a persistently abnormal yellow discharge, which could not be distinguished by the patient from urinary leaks. After a complete diagnostic work-up, the patient was identified as a candidate for hysterectomy due to abnormal vaginal bleeding resistant to megestrol acetate, family history of malignancy, and abnormal vaginal discharge. Laparotomy revealed unusual left fallopian tube features (large, bulky, and vegetative), suggesting malignancy. The intraoperative frozen-section analysis of the left fallopian tube and the ovarian specimens indicated the mass as a high-grade serous carcinoma of the fallopian tube. Total abdominal hysterectomy, bilateral salpingo-oophorectomy, and partial omentectomy were performed for the patient. The definitive histopathological diagnosis was high-grade serous carcinoma of the left fallopian tube (stage 2b) with omental involvement, without any evidence of lymphovascular invasion. High-grade serous carcinoma of the fallopian tube is likely to have non-specific symptoms, causing a significant delay in diagnosis and treatment, which negatively affects the prognosis and survival of these patients.

Limited benefit and high financial burden of drugs used to manage cancer-associated anorexia/cachexia syndrome (CACS).

55 Background: To date, drugs used for CACS have limited efficacy and may have unwanted side effects. Despite this, clinicians commonly prescribe certain drugs for CACS, adding financial burden to patients through out-of-pocket costs near or at the end of life. We sought to describe the range of costs of the multiple drugs commonly used to manage CACS. Methods: We reviewed oncology, nutrition, and supportive care guidelines (ASCO, ESMO, ESPEN, MASCC) and compiled a list of drugs recommended for CACS. We also included drugs commonly used off-label in clinical practice as identified by study authors. Using GoodRx.com, we extracted available formulations (e.g., tablet [tab] vs capsule [cap] vs oral disintegrating tablet [ODT] vs solution [sol]), and brand name vs generic products for each drug. We identified the average retail price, and the lowest price with coupons, for each formulation using the most commonly used dosage for a 2-week period (typical fill). The average retail price is the cash price for consumers without prescription drug coverage. The lowest price represents a discounted, ‘’best case’’ scenario of out-of-pocket costs for patients without prescription drug coverage. We collected data using the zip code 10065 in May 2021 to describe the range of costs of these drug formulations. Results: We included 7 drugs available in 20 formulations (Table). For a 2-week fill, the least expensive options included generic olanzapine 5 mg tab (once daily) and generic mirtazapine 15 mg tab (once daily), costing $4.50 per fill. Brand-name solutions were costly, ranging from $605.50 (megestrol acetate, Megace ES) to $1,156.30 (dronabinol, Syndros). Costs between formulations of the same drug/dosage varied widely: for olanzapine 5 mg, the lowest price varied from $4.50 [generic, tab] to $238.40 [Zyprexa zydis, brand-name, ODT]. Conclusions: We found that the costs of drugs used for CACS are highly variable, ranging from &lt; $5 to &gt; $1000 per fill. Overall there is limited data supporting use of drugs for managing CACS. Thus, our findings can help guide patient-clinician discussions about the risk/benefit ratio of a prescription for managing CACS, while highlighting the importance of seeking less expensive formulations when possible.[Table: see text]

Megestrol acetate is a specific inducer of CYP3A4 mediated by human pregnane X receptor.

Megestrol acetate is a synthetic progestogen used to treat some cancers and cancer-associated cachexia, but its potential interactions with other drugs are not well known. This study aims to determine the regulation of drug metabolizing enzymes by megestrol acetate. Primary human hepatocytes were treated and analyzed by PCR array to identify genes involved in drug metabolism that are impacted by megestrol acetate. P450 3A4 (CYP3A4) reporter gene assay and HPLC analyses of nifedipine metabolites were used to determine CYP3A4 gene expression and activities. Competitive ligand binding assay was used to determine the affinity of megestrol acetate toward human pregnane x receptor (hPXR). Electrophoretic mobility shift assay and mammalian two hybrid assay were used to determine the mechanism of megestrol to activate hPXR. The levels and activities of CYP3A4 were significantly induced (> 4-folds) by megestrol acetate in human hepatocytes and HepG2 cells. Megestrol treatment induced CYP3A4 through the activation of hPXR, a ligand-activated transcription factor that plays a role in drug metabolism and transport. Other tested nuclear receptors showed no response. The mechanism studies showed that megestrol activated hPXR by binding to the ligand binding domain (LBD) of hPXR and increasing the recruitment of the cofactors such as steroid receptor cofactor (SRC-1). The results suggest that megestrol acetate is a specific inducer of CYP3A4 mediated by hPXR and therefore has the potential to cause drug interactions, especially in the co-administration with drugs that are substrates of CYP3A4.

Preparation of Aspirin Nanosuspension by Antisolvent Precipitation Method

Preparation of Aspirin Nanosuspension by Antisolvent Precipitation Method

Effect of Megestrol Acetate Combined With Oral Nutrition Supplement in Malnourished Lung Cancer Patients: A Single-Center Prospective Cohort Study.

Background: The optimal treatment of cancer-related malnutrition remains unknown. A single-center prospective cohort study was performed to compare the efficacy of megestrol acetate (MA) combined with oral nutrition supplement (ONS) and MA alone for the treatment of lung cancer-related malnutrition.Methods: 76 eligible patients were prospectively enrolled in two arms, Arm 1 patients (n = 40, 52.6%) received MA 160 mg/d, and Arm 2 patients (n = 36, 47.4%) received MA 160 mg/d combined with ONS 55.8 g/t.i.d, all orally. All patients received anticancer therapy. Treatment duration was 3 months. The primary endpoints were improvements in body mass index (BMI) and Eastern Cooperative Oncology Group (ECOG) score. Secondary endpoints were assessed by appetite, mid-upper arm circumference (MAC), serum pre-albumin levels, and serum albumin levels.Results: Baseline levels were comparable between Arm 1 and Arm 2 patients. Compared with Arm 1, primary endpoints (BMI, P = 0.018; ECOG, P = 0.022) and secondary endpoints (MAC, P = 0.025; serum pre-albumin, P = 0.043; and serum albumin, P = 0.034) were improved significantly after treatment in Arm 2. While toxicity was negligible and comparable between Arm 1 and Arm 2.Conclusion: MA combined with ONS may be an effective and safe treatment option for lung cancer-related malnutrition patients.Clinical Trial Registration:www.clinicaltrials.gov, identifier ChiCTR2100049007.

Combination of traditional herbal medicine for the treatment of cancer-induced Anorexia/Cachexia: A pilot, randomized, double-blinded and placebo-controlled clinical trial

PurposeMany therapeutic approaches have been studied for the treatment of cancer-induced cachexia; however, except megestrol acetate, there is still no documented modality.The aim of this study was to evaluate the possible protective effect of several traditional herbal medicines, including Cichorium intybus, Trigonella foenum graecum, Daucus carotta, Hordeum vulgare, Foeniculum vulgare, Soya beans, peas in the management of cancer-induced cachexia/anorexia in patients with solid tumors. MethodsAdult patients suffering from advanced solid tumors with weight loss equal or greater than 5% within two previous months, during the intake of a high dose of megestrol (160 mg/day) as a routine treatment for cancer-induced cachexia, were included. Patients were randomly assigned to receive either one sachet of herbal combination or placebo, three times per day for 4 weeks, orally. Weight changes, anthropometric indices, and scores such as Edmonton Symptom Assessment Scale (ESAS), Functional Assessment of Anorexia/Cachexinorexia/Cachexia Therapy (FAACT), and European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 version 3.0 were assessed before and after the intervention. ResultsFifty-five patients completed the 4-week follow-up. Patients who had received herbal combination gained 0.9 kg weight, in comparison with a weight loss of 0.53 kg in the placebo group (P < 0.001). Improvement in quality of life and FAACT scores were not significant in each group (P > 0.05). The ESAS questionnaire assessment indicated that there was a significant improvement in two indices, including appetite (P < .001) and fatigue (P = .008), in the intervention group. ConclusionThis study has demonstrated that the traditional herbal combination is safe and effective in the prevention of weight loss, improvement of appetite and fatigue, in advanced cancer patients.

PPOS Protocol Effectively Improves the IVF Outcome Without Increasing the Recurrence Rate in Early Endometrioid Endometrial Cancer and Atypical Endometrial Hyperplasia Patients After Fertility Preserving Treatment.

Objective: To investigate the effectiveness and recurrence risk of different ovulation stimulation protocols in early-stage endometrioid endometrial cancer (EEC) and atypical endometrial hyperplasia (AEH) patients after successful fertility preserving treatment.Design: A retrospective review of clinical files between June 2012 and July 2018.Setting: University hospital.Patients: Ninety seven women (74 AEH and 23 early-stage EEC patients) underwent in vitro fertilization (IVF) and frozen-thawed embryo transfer (FET) after successful fertility preserving treatment. All patients received megestrol acetate which was initiated immediately after AEH or EEC diagnosis by hysteroscopy. Fertility treatment was initiated after confirmation of complete response by two consecutive hysteroscopic evaluations and endometrium biopsy in a 3-month interval. Women with tubal factors underwent IVF treatment directly. Women who failed to conceive spontaneously within 12 months or after other infertility treatments like ovulation induction for 6 consecutive months or 2 consecutive artificial insemination failures were also offered IVF treatment.Main Outcome Measure (s): The clinical and laboratory embryo data, clinical pregnancy outcomes and endometrial disease recurrence rates.Results: Compared with the standard regimen group, the good-quality embryo rate was higher in progestin primed ovarian stimulation (PPOS) regimen group (P = 0.034). Univariate analysis showed significant differences in age (P = 0.033), treatment time of endometrial lesions (P < 0.001), and duration of Gn treatment (P = 0.018) between the recurrent and non-recurrent groups. In the adjusted model of multivariate logistic regression analysis, the age (P = 0.014) at ovulation induction and treatment time of endometrial lesions (P < 0.001) were significantly correlated with the recurrence of endometrial disease.Conclusions: The PPOS protocol is a feasible and safe strategy to stimulate ovulation during IVF after fertility preservation therapy, and the age at ovulation induction and treatment time of endometrial lesions are two stable predictors of recurrence in endometrial diseases.

Megestrol acetate drives endometrial carcinoma cell senescence via interacting with progesterone receptor B/FOXO1 axis.

Megestrol acetate is a common and efficient anticancer progesterone. To explore the activity and the therapeutic mechanisms of megestrol acetate in endometrial cancer, human endometrial cancer cell lines Ishikawa and HHUA overexpressing progesterone receptor A (PR-A) and progesterone receptor B (PR-B) were treated with megestrol acetate. Cell viability, apoptosis, cycle arrest, and senescence, as well as the expressions of p21 and p16, two hallmarks of cellular senescence, were evaluated. Compared with the control, >10 nmol/L megestrol acetate treatment could significantly reduce endometrial cancer cell growth, and induce the irreversible G1 arrest and cell senescence. The expression of cyclin D1 in megestrol acetate treated cells was downregulated, while the expressions of p21 and p16 were upregulated via PR-B isoform. FOXO1 inhibitor AS1842856 could significantly abrogate megestrol acetate-induced cell senescence, suggesting that FOXO1 was involved in megestrol acetate/PR-B axis. These findings may provide a new understanding for the treatment of human endometrial cancer.

DESLORELIN (SUPRELORIN®) USE IN NORTH AMERICAN AND EUROPEAN ZOOS AND AQUARIUMS: TAXONOMIC SCOPE, DOSING, AND EFFICACY.

The Association of Zoos and Aquariums Reproductive Management Center (RMC) in the US and the European Association of Zoos and Aquaria Reproductive Management Group (RMG) in Europe monitor efficacy of contraceptive products in participating institutions and use those results to inform contraceptive recommendations. This study used the joint RMC-RMG Contraception Database to analyze efficacy of deslorelin implants (Suprelorin®), a contraceptive used in a wide range of mammalian taxa. More recently its use has increased in birds and in some reptiles and fish. Deslorelin, a gonadotropin-releasing hormone (GnRH) agonist, stimulates the reproductive system before downregulating receptors on pituitary cells that produce hormones that stimulate gonadal steroids in both males (testosterone) and females (estradiol and progesterone), interrupting sperm production and ovulation, respectively. Nevertheless, it has been used mostly in females. Efficacy has been high in mammals, with failures resulting in offspring in only 1.3% of treated individuals and 0.5% of treatment bouts. The failure rate has been higher in birds, with 14.7% of individuals in 7.2% of bouts producing eggs, perhaps reflecting differences in avian GnRH molecules. Too few reptiles and fish have been treated for meaningful analysis. Although deslorelin appears very safe, a possible exception exists in carnivores, because the stimulatory phase can result in ovulation and subsequent sustained progesterone secretion that may cause endometrial pathology. However, the stimulatory phase can be prevented by treatment with megestrol acetate for 7 d before and 7 d after implant insertion. The two current formulations of Suprelorin are effective for minimums of 6 (4.7 mg) or 12 mo (9.4 mg). The data indicate that Suprelorin is an effective and safe contraceptive option for female mammals, although it may not be effective in males of some mammalian species. Further research is needed to ascertain its usefulness in nonmammalian taxa.

Development of Simultaneous Determination Method of a Pregnan Steroid with Gestagenic Activity – Gestobutanoil and Two its Metabolites in Rat Serum

Introduction. Gestobutanoil is a synthetic pregnane steroid with gestagenic activity. Gestobutanoil has two pharmacologically active metabolites (AMOL and megestrol acetate). This implies the need for a detailed study of the kinetics of metabolites. It is rational to combine the study of the pharmacokinetics of gestobutanoil and its metabolites (AMOL and megestrol acetate). The simultaneous determination of several analytes in the rats’ serum can be carried out using chromatography-mass-spectrometry.Aim. Development of an analytical method for the simultaneous determination of gestobutanoil and two its metabolites in a biomatrix (rat serum).Materials and methods. The following methods were used to determine gestobutanoyl and two its metabolites in a biological matrix: GC-MS, HPLCESI-MS, HPLC-ESI-MS with derivatization, HPLC-APCI-MS.Results and discussion. When working with GC-MS, the chromatographic peaks of gestobutanoyl, AMOL, and megestrol acetate were strongly blurred and superimposed on each other, which is apparently due to the thermolability of the substances. The GC-MS method was abandoned in favor of HPLC. Analytes were separated by HPLC gradient elution on a C18 column. ESI ionization did not give typical protonated ions of gestobutanoyl and AMOL, and the intense signals of their cationized ions and fragment ions, which were observed in the spectra of AMOL and gestobutanoyl, could not ensure the reproducibility of the spectra, since the conditions of their formation are not suitable for routine analysis. Derivatization of analytes to form oximes and substituted hydrazones did not give the expected reaction products for HPLC-ESI-MS. APCI made it possible to remove intense cationized ions from the spectra of gestobutanoyl and AMOL and to increase the reliability of the method. The HPLCAPCI-MS technique was reproduced on model rat blood serum.Conclusion. An HPLC-MS method was developed for the simultaneous determination of gestobutanoyl, megestrol acetate, and AMOL. The technique was tested on a model rat blood serum containing all three analytes.

Effect of multimodal intervention care on cachexia in patients with advanced cancer compared to conventional management (MIRACLE): An open-label, phase 2 trial.

TPS12134 Background: Cancer Cachexia (CC) is a multi-factorial process characterized by progressive weight loss, muscle mass and fat tissue wasting, and adversely affecting the quality of life and survival in patients with advanced stage of cancer. CC has a complex and multi-factorial pathophysiology, and there is no established standard treatment. Once it occurs, it is often irreversible and also difficult to suppress the its progression with any single treatment modality. We are conducting an open-label, parallel, randomized phase 2 trial to investigate the effect on preventing or alleviating cancer cachexia and safety of a multi-modal intervention including anti-inflammation, omega-3-fatty acids, nutritional supplement with counselling, physical exercise, psychiatric intervention as well as bojungikki-tang, which mediates immune-modulation and reverse inflammation-related chronic consumptive wasting condition as a complementary and alternative medicine compared to patients receiving best supportive care. Methods: Eligible criteria included patients with recurrent or metastatic gastrointestinal (gastric, colorectal and pancreaticobiliary) as well as lung cancer undergoing active palliative chemotherapy. Patients who have already developed refractory cachexia (ie, low performance status, difficult to take medications orally or visit the hospital to exercise) are excluded. Patients are randomized into experimental arm (Multi-modal intervention care: MIC) versus control arm (Conventional Palliative Care, CPC). MIC are comprised of 1) daily oral medications; ibuprofen 400 mg three times a day, omega-3-fatty acid 1 g twice a day, Bojungikki-tang 3.75g twice a day, oral nutritional supplement (HAMONILAN SOLN) 200 ml twice a day, and 2) clinical interventions; weekly physical exercise (60 minutes per visit), psychiatric assessment on every other week, and nutritional counselling total four times during the study period. CPC included basic nutritional counselling for two times provided by National Health Insurance Service, and megestrol acetate as needed (ie, anorexia ≥ Grade 2). All interventions were provided during 12 weeks per subject. Co-primary outcomes are change of total lean body mass and handgrip strength from the baseline. Secondary outcomes included change of fat mass and total body mass, lean body mass, Functional Assessment of Anorexia/Cachexia Treatment (FAACT) score, quality of life assessed by EORTC QLQ-C30, Spleen Qi Deficiency questionnaire (SQDQ), and overall survival. Total 112 patients will be assigned in the two arms (56 in each group). We have started the study in October 2020. At the time of submission, 26 patients were enrolled. Planned period of enrollment is 18 months. Clinical trial information: Clinical Research information Service, CRIS (KCT0004967). Clinical trial information: KCT0004967.

Evaluating the role of aromatase inhibitors (AIs) in the treatment of endometrial stromal sarcomas (ESS).

5575 Background: Endometrial stromal sarcomas (ESS) account for &lt; 20% of uterine sarcomas. They usually express estrogen and progesterone receptors (ER/PR) and are considered hormone sensitive. Due to the rarity of these tumors, large clinical trials studying optimal treatment have not been possible. This study represents the largest retrospective study of ESS treated with AI. Methods: The clinicopathological variables and outcomes of patients (pts) with pathologically confirmed low grade ESS treated with AI at our institution between 1998-2020 were recorded. Results: 48 pts with ESS treated with AI were identified. They had a median age of 54 years (range 23-84) and BMI of 27 (range 20-50). 79% were white. 6 (12%), 9 (19%), 14 (29%) and 19 pts (40%) had stage 1,2,3,4 ESS, respectively. 37 (77%) were ER+/PR+; 2 (4%) ER+/PR- and 9 pts (19%) had unknown ER/PR status. All pts were postmenopausal at AI initiation. 12 pts (25%) had a synchronous cancer (5 of these had breast cancer {3 of the 5 presented post tamoxifen}). 23 pts (48%) received megestrol acetate and 25 (52%) an AI as first line hormonal manipulation. During their disease course, 35 pts (73%) received letrozole, 21 (44%) anastrozole and 19 (39.6%) exemestane. 22 pts (46%) were treated with more than one AI. 28 pts (58%) reported side-effects; arthralgia (33%) being the most common. 10 pts (21%) discontinued AI due to toxicity; 12 pts (25%) switched AI for toxicity (with improved tolerance in 67% of these pts). Among the 24 pts (50%) with measurable disease there were 2 partial responses (objective response rate of 8.3%). 1-year disease control rate (DCR) was (79%) for all pts and 58% in stage 4 disease. Median PFS for 1st line AI was 161.6 months (95% CI 48.5 to 274.7). Conclusions: This study represents the largest study of AI use in ESS to date. We found the ORR to be more modest than previously reported. The majority of pts had prolonged stable disease with a DCR of 58% even in stage 4 disease. Pts who progress on one AI may benefit from trial of a 2nd AI. A phase 2 study of interruption versus maintenance AI in locally advanced/metastatic ESS is currently underway (NCT03624244).