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1.
Ann Palliat Med ; 8(1): 33-42, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30525763

RESUMO

Cancer cachexia (CC) is common in advanced cancer and is accompanied by negative effects on health-related quality of life (HRQOL). However, methods to identify the impact of CC on HRQOL are limited. Single questionnaire items may provide insight on the effect of CC on HRQOL. Specifically, the use of "feeling of wellbeing" (FWB) on the Edmonton Symptom Assessment System (ESAS) questionnaire and the Distress Thermometer (DT) have been explored. Assessing how these two surrogate measures of HRQOL are impacted among CC stages and what drives these negative effects may allow for focused treatments. Five-hundred and twelve patients referred to a Cancer Rehabilitation Program completed the ESAS, with the question on FWB and the DT at baseline. Patients were separated into CC stages: non-cachexia (NC), pre-cachexia (PC), cachexia (C), refractory cachexia (RC). A mixed model ANOVA with post hoc Tukey adjustment was used to compare means of FWB and distress among the CC stages. To understand what was driving the differences between CC stages, a robust regression model was created with either distress or FWB as the outcome measure, dependent on the other measures in ESAS, age and sex. Finally, the use of cannabinoids in treating appetite loss was examined, as it has a detrimental effect on FWB; 54 patients underwent cannabinoid treatment for appetite loss within a community-based, physician-lead, medical cannabis clinic. A t-test to assess changes in ESAS appetite score after 3 months of cannabinoid treatment was examined. RC patients had a significantly poorer sense of wellbeing than the other cachexia stages (RC: 6.07±0.33). Significant differences in distress were identified between RC patients and those with NC and C, but not with PC (RC: 4.87±0.38, NC: 3.35±0.26, PC: 4.11±0.30, C: 3.60±0.28). FWB was negatively affected by worsening appetite in all CC stages except NC (PC: 0.19±0.08, P=0.022; C: 0.26±0.06, P<0.001; RC: 0.23±0.08, P=0.007). ESAS score for lack of appetite significantly improved between baseline (5.07±3.21) and follow-up (3.56±3.15, P=0.003) after cannabinoid treatment, with no significant difference in weight (baseline: 70.7±14.6 kg, 3-month follow-up: 71.0±14.8 kg). Future research should validate both multidimensional and single-item tools to measure HRQOL in patients at different stages of CC. Improvement of HRQOL via appetite stimulation, may be achieved through a multidisciplinary approach, which includes cannabinoid therapy.


Assuntos
Caquexia/psicologia , Neoplasias/psicologia , Qualidade de Vida/psicologia , Corticosteroides/uso terapêutico , Anorexia/etiologia , Estimulantes do Apetite/uso terapêutico , Canabinoides/uso terapêutico , Ciproeptadina/uso terapêutico , Feminino , Nível de Saúde , Humanos , Hidrazinas/uso terapêutico , Masculino , Acetato de Megestrol/uso terapêutico , Pessoa de Meia-Idade , Oligopeptídeos/uso terapêutico , Antagonistas da Serotonina/uso terapêutico , Índice de Gravidade de Doença , Estresse Psicológico/etiologia , Inquéritos e Questionários
2.
Gynecol Oncol ; 152(2): 278-285, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30501904

RESUMO

OBJECTIVES: The role of endocrine therapy (ET) in high grade serous ovarian carcinoma (HGSOC) is poorly defined due to the lack of phase III data and significant heterogeneity of clinical trials performed. In this study, we sought to identify predictive factors of endocrine sensitivity in HGSOC. METHODS: HGSOC patients who received at least four weeks of ET for relapsed disease following one line of chemotherapy at the Edinburgh Cancer Centre were identified. Exclusion criteria were use of endocrine therapy as maintenance therapy or of unknown duration. Duration of therapy and best CA125 response as per modified GCIG criteria were recorded. Oestrogen receptor (ER) histoscore, treatment free interval, prior lines of chemotherapy, and type of ET were evaluated as predictive factors. RESULTS: Of 431 patients identified, 269 were eligible (77.0% letrozole, 18.6% tamoxifen, 2.2% megesterol acetate, 2.2% other). The median duration of therapy was 126 days (range 28-1427 days). 32.7% remained on ET for ≥180 days and 14.1% for ≥365 days. The CA125 response and clinical benefit rates (response or stable disease) were 8.1% and 40.1% respectively. ER histoscore >200 (P = 0.0016) and a treatment free interval of ≥180 days (P < 0.0001) were independent predictive factors upon multivariable analysis. CONCLUSIONS: ET should be considered as a viable strategy to defer subsequent chemotherapy for relapsed HGSOC. Patients with an ER histoscore >200 and a treatment free interval of ≥180 days are most likely to derive benefit.


Assuntos
Antineoplásicos Hormonais/uso terapêutico , Cistadenocarcinoma Seroso/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígeno Ca-125/metabolismo , Cistadenocarcinoma Seroso/metabolismo , Cistadenocarcinoma Seroso/patologia , Feminino , Humanos , Letrozol/uso terapêutico , Acetato de Megestrol/uso terapêutico , Proteínas de Membrana/metabolismo , Pessoa de Meia-Idade , Gradação de Tumores , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/patologia , Valor Preditivo dos Testes , Receptores Estrogênicos/metabolismo , Estudos Retrospectivos , Tamoxifeno/uso terapêutico
3.
Ceska Gynekol ; 83(4): 263-270, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30441956

RESUMO

OBJECTIVE: The aim of the study was to describe the role of hormonal therapy in the treatment of malignant uterine tumors, indications, the effect of the treatment and to verify its safety in our study cohort. We also present an overview of recent studies on that topic. DESIGN: Unicentric retrospective observational study and review of recent literature. SETTING: Department of Obstetrics and Gynecology, Masaryk University, University Hospital Brno. METHODS: The results of recent relevant studies and reviews published in English until December 2017 were used for the review. The publications were searched using the PubMed server. All patients diagnosed in our oncogynecological center between 2010 and 2016 and who were treated hormonally - either in primary therapy or in relapse settings, were included in our study. We were interested in age, BMI, stage of disease, histological type and grade of tumor, occurrence of adverse effects, duration of survival, reasons for choosing hormonal therapy. Medroxyprogesterone-acetate or megestrol-acetate was used in the treatment. RESULTS: Between 2010 and 2016, 415 malignant tumors of the uterus were diagnosed in our oncology center. Recurrence of the disease occurred in 31 patients (8%), on average 16 months after primary treatment. Primary hormonal therapy was used in only 19 patients (5%), mostly because of contraindications of another treatment due to high age, comorbidities or obesity. Median age of patients was 83 years, mean BMI 41, median survival of patients who died was 8 months. Five patients (16%) were treated hormonally for the recurrence. Median survival from diagnosis of recurrence was 20 months. One patient (4%) experienced partial pulmonary embolism. CONCLUSION: Hormonal therapy plays an irreplaceable role in uterine cancer patients, especially in primary non-operable patients, in treatment of a relapse, or in a fertility-sparing procedure. This treatment option is safe, with minimal adverse effects.


Assuntos
Antineoplásicos Hormonais/uso terapêutico , Neoplasias Uterinas/tratamento farmacológico , Idoso de 80 Anos ou mais , Feminino , Humanos , Acetato de Medroxiprogesterona/uso terapêutico , Acetato de Megestrol/uso terapêutico , Recidiva Local de Neoplasia/patologia , Estudos Retrospectivos , Neoplasias Uterinas/mortalidade
4.
J Cachexia Sarcopenia Muscle ; 9(3): 444-452, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29542279

RESUMO

In 1993, megestrol acetate (MA) was approved by the US Food and Drug Administration for the treatment of anorexia, cachexia, or unexplained weight loss in patients with acquired immunodeficiency syndrome. The mechanism by which MA increases appetite is unknown, and its effectiveness for anorexia and cachexia in neoplastic, elderly, and acquired immunodeficiency syndrome patients is under investigation. This is an updated version of a Cochrane systematic review first published in 2005 and later updated in 2013 entitled 'Megestrol acetate for the treatment of anorexia-cachexia syndrome'. MA vs. placebo: in studies where MA was compared with placebo, the overall results showed that MA patients gained weight (mean difference, MD 2.25 kg, 95% CI [1.19, 3.3]) but did not gain quality of life (QOL) (standarized mean difference, SMD 0.5, 95% CI [-0.13, 1.13]), with more adverse events (relative risk, RR 1.46, 95% CI [1.05, 2.04]), but no difference in deaths (RR 1.26, 95% CI [0.70, 2.27]). MA vs. no treatment: MA patients gained weight (MD 1.45 kg, 95% CI [0.15, 2.75]) but did not gain QOL (standardized mean difference 3.89 95% CI [-14, 6.28]). There was no increase in adverse events (RR 0.90, 95% CI [0.39, 2.08]) or deaths (RR 1.01, 95% CI [0.42, 2.45]). MA vs. active drugs: MA patients gained weight (MD 2.5 kg, 95% CI [0.37, 4.64]) but did not gain QOL (MD 0.20 95% CI [-0.02, 0.43]) and did not report an increase in adverse events (RR 1.05 95% CI [0.95, 1.16]) or in deaths (RR 1.53, 95% CI [1.02, 2.29]) Different doses of MA: in studies where lower doses of MA were compared with higher doses of MA, we did not find differences either in weight gain (MD -0.94 kg, 95% CI [-3.33, 1.45]), QOL (MD 0.31 95% CI [-0.19, 0.81]), or adverse events (RR 1.34, 95% CI [0.65, 2.76]). Thus, we cannot reach a conclusion for an optimal dose of MA.


Assuntos
Anorexia/tratamento farmacológico , Estimulantes do Apetite/uso terapêutico , Caquexia/tratamento farmacológico , Acetato de Megestrol/uso terapêutico , Anorexia/etiologia , Anorexia/mortalidade , Estimulantes do Apetite/farmacologia , Caquexia/etiologia , Caquexia/mortalidade , Humanos , Acetato de Megestrol/farmacologia , Prognóstico , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Síndrome , Resultado do Tratamento
5.
J Gynecol Oncol ; 29(3): e35, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29533020

RESUMO

OBJECTIVE: Our previous study showed that insulin resistance (IR) was related to endometrial hyperplasia as well as endometrial cancer. But the exact impact of IR on fertility-sparing treatment in endometrial hyperplasic disease is unclear. This study investigated how IR affects fertility-sparing treatment in endometrial atypical hyperplasia (EAH) patients. METHODS: The 151 EAH patients received fertility-sparing treatment were retrospectively investigated. All patients received high-dose progestin combined with hysteroscopy. Therapeutic effects were evaluated by hysteroscopy every 3 months during the treatment. RESULTS: The median age was 33.0 years old (range, 21-54 years old). Sixty-one patients (40.4%) were insulin resistant. Three patients were excluded from the analysis because they chose hysterectomy within 3 months after initiation of progestin treatment. The 141 out of 148 (95.3%) patients achieved complete response (CR). No difference was found in cumulative CR rate between those with or without IR (90.2% vs. 95.6%, p=0.320). IR significantly affected therapeutic duration to achieve CR (8.1±0.5 months with IR vs. 6.1±0.4 months without IR, p=0.004). Overweight (body mass index [BMI]≥25 kg/m²) was associated with higher risk of treatment failure (odds ratio=5.61; 95% confidence interval=1.11-28.35; p=0.040) and longer therapeutic duration to achieve CR (7.6±0.5 months vs. 6.3±0.4 months, p=0.019). EAH patients with both IR and overweight (IR+BMI+) had the longest therapeutic time compared with other patients (8.8±0.6 months vs. 5.6±0.7, 6.3±0.4, and 6.4±0.8 months for IR-BMI+, IR-BMI-, and IR+BMI-, respectively, p=0.006). CONCLUSION: IR and overweight were associated with longer therapeutic duration in EAH patients receiving progestin-based fertility-sparing treatment.


Assuntos
Hiperplasia Endometrial/tratamento farmacológico , Preservação da Fertilidade , Resistência à Insulina , Sobrepeso/complicações , Adulto , Índice de Massa Corporal , Hiperplasia Endometrial/fisiopatologia , Feminino , Humanos , Acetato de Megestrol/uso terapêutico , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Tempo , Adulto Jovem
6.
Support Care Cancer ; 26(7): 2479-2489, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29442239

RESUMO

PURPOSE: Previous studies reported promising efficacy for celecoxib in the treatment of cancer cachexia. We designed this study to test the hypothesis that combination therapy with megestrol acetate (MA) plus celecoxib is superior to MA alone. METHODS: Ninety eligible gastrointestinal cancer patients randomly received either MA 320 mg/day plus placebo (arm1) or MA 320 mg/day plus celecoxib 200 mg/day (arm2). Patients were evaluated at baseline, then 1 and 2 months after starting interventions. The primary outcome was body weight. Secondary outcomes were quality of life, grip strength, appetite score, performance status, plasma albumin, CRP, IL-6, and Glasgow Prognostic Score. RESULTS: Patients were comparable at baseline. Sixty patients were assessable for the first month and 33 patients for the second month. After 2 months, patients in arm1 (MA + placebo) and arm2 (MA + celecoxib) experienced 4.0 ± 3.4 and 2.2 ± 3.6Kg of weight gain respectively (P = 0.163). Changes relative to baseline were statistically significant in both arms of the study (P = 0.001). Regarding secondary outcomes, comparisons between groups did not show any statistically significant difference, but within-group changes were significant in both arms of the study. CONCLUSION: Since both MA alone and MA plus celecoxib are associated with improvement of cachexia in GI cancer patients, this study failed to show that adding celecoxib (200 mg/day) to megestrol (320 mg/day) could enhance anti-cachexic effects of megestrol.


Assuntos
Anorexia/tratamento farmacológico , Antineoplásicos Hormonais/uso terapêutico , Caquexia/tratamento farmacológico , Celecoxib/uso terapêutico , Terapia Combinada/métodos , Neoplasias Gastrointestinais/complicações , Acetato de Megestrol/uso terapêutico , Qualidade de Vida/psicologia , Antineoplásicos Hormonais/farmacologia , Celecoxib/farmacologia , Método Duplo-Cego , Feminino , Neoplasias Gastrointestinais/tratamento farmacológico , Neoplasias Gastrointestinais/patologia , Humanos , Masculino , Acetato de Megestrol/farmacologia , Pessoa de Meia-Idade , Estudos Prospectivos , Ganho de Peso
8.
Sci Rep ; 7(1): 12754, 2017 10 06.
Artigo em Inglês | MEDLINE | ID: mdl-28986550

RESUMO

Endometrial cancer is the most common gynecologic cancer in the United States and its incidence and mortality has been rising over the past decade. Few treatment options are available for patients with advanced and recurring endometrial cancers. Novel therapies, which are frequently toxic, are difficult to establish in this patient population which tends to be older and plagued by comorbidities such as diabetes mellitus and hypertension. Therefore, novel, non-toxic therapies are urgently needed. Megestrol acetate is a frequently used drug in endometrial cancer patients. However, its response rate is only 20-30%. To enhance the activity of megestrol acetate in endometrial cancer patients, we explored the potential of combining natural supplements with megestrol acetate and found that the addition of the natural phenolic compound, pterostilbene, to megestrol acetate resulted in a synergistic inhibition of cancer cell growth in vitro and an enhanced reduction of tumor growth in a xenograft mouse model. In addition, dual treatment led to attenuation of signaling pathways, as well as cell cycle and survival pathways. Our results demonstrated for the first time that the anti-tumor activity of megestrol acetate can be enhanced by combining with pterostilbene, providing an insight into the potential application of pterostilbene and megestrol acetate combination for the treatment of endometrial cancer.


Assuntos
Antineoplásicos/uso terapêutico , Produtos Biológicos/uso terapêutico , Neoplasias do Endométrio/tratamento farmacológico , Acetato de Megestrol/uso terapêutico , Fenóis/uso terapêutico , Estilbenos/uso terapêutico , Animais , Antineoplásicos/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Produtos Biológicos/farmacologia , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Sinergismo Farmacológico , Neoplasias do Endométrio/patologia , Feminino , Humanos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Acetato de Megestrol/farmacologia , Camundongos Nus , Fenóis/farmacologia , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais/efeitos dos fármacos , Estilbenos/farmacologia , Ensaios Antitumorais Modelo de Xenoenxerto
9.
Cochrane Database Syst Rev ; 10: CD012214, 2017 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-29077194

RESUMO

BACKGROUND: Endometrial cancer is one of the most common gynaecological cancers in the world. Rates of endometrial cancer are rising, in part because of rising obesity rates. Endometrial hyperplasia is a precancerous condition in women that can lead to endometrial cancer if left untreated. Endometrial hyperplasia occurs more commonly than endometrial cancer. Progesterone tablets currently used to treat women with endometrial hyperplasia are associated with adverse effects in up to 84% of women. The levonorgestrel intrauterine device (Mirena Coil, Bayer HealthCare Pharmaceuticals, Inc., Whippany, NJ, USA) may improve compliance, but it is invasive, is not acceptable to all women, and is associated with irregular vaginal bleeding in 82% of cases. Therefore, an alternative treatment for women with endometrial hyperplasia is needed. Metformin, a drug that is often used to treat people with diabetes, has been shown in some human studies to reverse endometrial hyperplasia. However, the effectiveness and safety of metformin for treatment of endometrial hyperplasia remain uncertain. OBJECTIVES: To determine the effectiveness and safety of metformin in treating women with endometrial hyperplasia. SEARCH METHODS: We searched the Cochrane Gynaecology and Fertility Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), PubMed, Google Scholar, OpenGrey, Latin American Caribbean Health Sciences Literature (LILACS), and two trials registers from inception to 10 January 2017. We searched the bibliographies of all included studies and reviews on this topic. We also handsearched the conference abstracts of the European Society of Human Reproduction and Embryology (ESHRE) 2015 and the American Society for Reproductive Medicine (ASRM) 2015. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and cross-over trials comparing metformin (used alone or in combination with other medical therapies) versus placebo or no treatment, any conventional medical treatment, or any other active intervention for women with histologically confirmed endometrial hyperplasia of any type. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies for eligibility, extracted data from included studies, and assessed the risk of bias of included studies. We resolved disagreements by discussion or by deferment to a third review author. When study details were missing, review authors contacted study authors. The primary outcome of this review was regression of endometrial hyperplasia histology (with or without atypia) towards normal histology. Secondary outcome measures included recurrence of endometrial hyperplasia, progression of endometrial hyperplasia to endometrial cancer, hysterectomy rate, abnormal uterine bleeding, health-related quality of life, and adverse effects during treatment. MAIN RESULTS: We included three RCTs in which a total of 77 women took part. We rated the quality of the evidence as very low for all outcomes owing to very serious risk of bias (associated with poor reporting, attrition, and limitations in study design) and imprecision.We performed a meta-analysis of two trials with 59 participants. When metformin was compared with megestrol acetate in women with endometrial hyperplasia, we found insufficient evidence to determine whether there were differences between groups for the following outcomes: regression of endometrial hyperplasia histology towards normal histology (odds ratio (OR) 3.34, 95% confidence interval (CI) 0.97 to 11.57, two RCTs, n = 59, very low-quality evidence), hysterectomy rates (OR 0.91, 95% CI 0.05 to 15.52, two RCTs, n = 59, very low-quality evidence), and rates of abnormal uterine bleeding (OR 0.91, 95% CI 0.05 to 15.52, two RCTs, n = 44 , very low-quality evidence). We found no data for recurrence of endometrial hyperplasia or health-related quality of life. Both studies (n = 59) provided data on progression of endometrial hyperplasia to endometrial cancer as well as one (n = 16) reporting some adverse effects in the metformin arm, notably nausea, thrombosis, lactic acidosis, abnormal liver and renal function among others.Another trial including 16 participants compared metformin plus megestrol acetate versus megestrol acetate alone in women with endometrial hyperplasia. We found insufficient evidence to determine whether there were differences between groups for the following outcomes: regression of endometrial hyperplasia histology towards normal histology (OR 9.00, 95% CI 0.94 to 86.52, one RCT, n = 16, very low-quality evidence), recurrence of endometrial hyperplasia among women who achieve regression (OR not estimable, no events recorded, one RCT, n = 8, very low-quality evidence), progression of endometrial hyperplasia to endometrial cancer (OR not estimable, no events recorded, one RCT, n = 13, very low-quality evidence), or hysterectomy rates (OR 0.29, 95% CI 0.01 to 8.37, one RCT, n = 16, very low-quality evidence). Investigators provided no data on abnormal uterine bleeding or health-related quality of life. In terms of adverse effects, three of eight participants (37.5%) in the metformin plus megestrol acetate study arm reported nausea. AUTHORS' CONCLUSIONS: At present, evidence is insufficient to support or refute the use of metformin alone or in combination with standard therapy - specifically, megestrol acetate - versus megestrol acetate alone, for treatment of endometrial hyperplasia. Robustly designed and adequately powered randomised controlled trials yielding long-term outcome data are needed to address this clinical question.


Assuntos
Hiperplasia Endometrial/tratamento farmacológico , Metformina/uso terapêutico , Lesões Pré-Cancerosas/tratamento farmacológico , Adulto , Idoso , Antineoplásicos Hormonais/efeitos adversos , Antineoplásicos Hormonais/uso terapêutico , Progressão da Doença , Hiperplasia Endometrial/cirurgia , Feminino , Humanos , Histerectomia/estatística & dados numéricos , Acetato de Megestrol/efeitos adversos , Acetato de Megestrol/uso terapêutico , Metformina/efeitos adversos , Pessoa de Meia-Idade , Lesões Pré-Cancerosas/cirurgia , Ensaios Clínicos Controlados Aleatórios como Assunto , Recidiva , Hemorragia Uterina/etiologia , Neoplasias Uterinas/etiologia , Neoplasias Uterinas/prevenção & controle
10.
Adv Ther ; 34(5): 1211-1220, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-28353144

RESUMO

INTRODUCTION: The present study was conducted as a pilot to compare the therapeutic effects and the potential side effects of oral Megestrol acetate and Letrozole in the treatment of simple hyperplasia in perimenopausal women. METHODS: The participants of this randomized clinical trial consisted of two groups of 25 women aged 44-50 presenting with abnormal uterine bleeding diagnosed with simple endometrial hyperplasia without cytologic atypia confirmed by transvaginal ultrasonography and biopsy. The first group received 40-mg doses of Megestrol acetate for 2 weeks per month for a total period of 2 months. The second group received 2.5-mg daily doses of Letrozole for a total period of 2 months. The differences in terms of quantitative measurements were analyzed using the independent two-sample t test and the paired t test. To compare the two groups in terms of the distribution of the categorical variables, Pearson's Chi square and Fisher's Exact tests were used at the significance level of 0.05 by Stata-9.2. RESULTS: Although the intervention led to significant improvements in both groups (P < .001), there was no difference between the groups in terms of accomplishing resolution (P = .74) [seven (28%) patients in the Letrozole group and five (20%) in the Megestrol group], while two patients in the Letrozole group and nine in the Megestrol group suffered from side effects, suggesting significantly lower side effects in the Letrozole group (P = .02). CONCLUSION: Letrozole and Megestrol acetate seem to have similar effects on the treatment of simple endometrial hyperplasia, the only difference being that Letrozole presents fewer side effects than Megestrol acetate in patients with this condition. FUNDING: Abnormal Uterine Bleeding Research Center of Semnan University of Medical Sciences, Semnan, Iran. TRIAL REGISTRATION: IRCT2015031011504N5.


Assuntos
Hiperplasia Endometrial/tratamento farmacológico , Acetato de Megestrol/uso terapêutico , Nitrilos/uso terapêutico , Triazóis/uso terapêutico , Administração Oral , Adulto , Feminino , Humanos , Letrozol , Pessoa de Meia-Idade , Projetos Piloto
11.
Cancer ; 123(9): 1545-1554, 2017 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-28026855

RESUMO

BACKGROUND: The incidence of endometrial cancer among young women is increasing. Some patients with low-grade endometrial cancer receive hormone therapy (HT) before surgery to preserve fertility. It is unclear whether this adversely affects survival. METHODS: Patients with localized, low-grade endometrial cancer who were aged <45 years were selected from the Surveillance, Epidemiology, and End Results database between 1993 and 2012. Propensity score matching was used to select comparable groups receiving HT or primary surgery. Cancer-specific and overall survival were measured using Kaplan-Meier methods. Hazard ratios and 95% confidence intervals (95% CIs) were estimated using Cox models adjusted for age, period of diagnosis, marital status, race, tumor grade, morphology, and previous radiotherapy. RESULTS: A total of 6339 women were included in the current study cohort, 161 of whom initially received HT and 6178 of whom received primary surgery. After 15 years of follow-up, all-cause mortality did not differ between the groups (HT group: 14.1% [95% CI, 6.7%-28.4%] and propensity score-matched primary surgery group: 9.3% [95% CI, 4.1%-20.5%]). Cancer-specific mortality appeared higher in patients treated with HT compared with those treated with primary surgery (9.2% [95% CI, 3.4%-24.0%] vs 2.1% [95% CI, 1.5%-2.8%]). However, this difference was driven by 3 late deaths in the HT group. Sensitivity analyses using a broader definition of cancer-specific mortality provided no statistical evidence of a survival difference between the treatment groups. The hazard ratio for the overall risk of death was 1.45 (95% CI, 0.44-4.74). CONCLUSIONS: Based on this population-based cohort, young patients with low-grade endometrial cancer appear to have excellent survival, regardless of the primary therapy chosen (HT vs primary surgery). The current selection of patients for HT to preserve fertility, which is managed carefully by experienced clinicians, does not appear to significantly worsen clinical outcomes. Cancer 2017;123:1545-1554. © 2017 American Cancer Society.


Assuntos
Antineoplásicos Hormonais/uso terapêutico , Carcinoma Endometrioide/tratamento farmacológico , Neoplasias do Endométrio/tratamento farmacológico , Preservação da Fertilidade/métodos , Histerectomia , Adulto , Carcinoma Endometrioide/mortalidade , Causas de Morte , Estudos de Coortes , Neoplasias do Endométrio/mortalidade , Feminino , Humanos , Estimativa de Kaplan-Meier , Medroxiprogesterona/uso terapêutico , Acetato de Medroxiprogesterona/uso terapêutico , Acetato de Megestrol/uso terapêutico , Gradação de Tumores , Pontuação de Propensão , Modelos de Riscos Proporcionais , Programa de SEER , Fatores de Tempo , Estados Unidos
12.
Int J Gynecol Cancer ; 27(2): 258-266, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27870712

RESUMO

OBJECTIVE: Advanced/metastatic or recurrent endometrial cancer has a poor prognosis. Malignant endometrial tissue has high steroid sulphatase (STS) activity. The aim of this study was to evaluate STS as a therapeutic target in patients with endometrial cancer. METHODS: This was a phase 2, multicenter, international, open-label, randomized (1:1), 2-arm study of the STS inhibitor oral irosustat 40 mg/d versus oral megestrol acetate 160 mg/d in women with advanced/metastatic or recurrent estrogen receptor-positive endometrial cancer. The primary end point was the proportion of patients without progression or death 6 months after start of treatment. Secondary end points included progression-free survival, time to progression, overall survival, and safety. RESULTS: Seventy-one patients were treated (36 with irosustat, 35 with megestrol acetate). The study was prematurely stopped after futility analysis. Overall, 36.1% and 54.1% of patients receiving irosustat or megestrol acetate had not progressed or died at 6 months, respectively. There were no statistically significant differences between irosustat and megestrol acetate in response and overall survival rates. Irosustat patients had a median progression-free survival of 16 weeks (90% confidence interval, 9.0-31.4) versus 40 weeks (90% confidence interval, 16.3-64.0) in megestrol acetate patients. Treatment-related adverse events occurred in 20 (55.6%) and 13 (37.1%) patients receiving irosustat or megestrol, respectively. Most adverse events in both groups were grade 1 or 2. CONCLUSIONS: Although irosustat monotherapy did not attain a level of activity sufficient for further development in patients with advanced/recurrent endometrial cancer, this study confirms the activity of hormonal treatment (megestrol acetate) for this indication.


Assuntos
Antineoplásicos Hormonais/uso terapêutico , Neoplasias do Endométrio/tratamento farmacológico , Acetato de Megestrol/uso terapêutico , Ácidos Sulfônicos/uso terapêutico , Idoso , Antineoplásicos Hormonais/efeitos adversos , Intervalo Livre de Doença , Neoplasias do Endométrio/metabolismo , Neoplasias do Endométrio/patologia , Feminino , Humanos , Acetato de Megestrol/efeitos adversos , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/metabolismo , Recidiva Local de Neoplasia/patologia , Receptores Estrogênicos/metabolismo , Ácidos Sulfônicos/efeitos adversos
13.
Basic Clin Pharmacol Toxicol ; 120(3): 270-277, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27639080

RESUMO

Megestrol acetate, an appetite stimulant with low bioavailability, shows increased bioavailability when taken together with food. However, the pharmacokinetic characteristics of megestrol acetate and its relation with food are not well understood. This study aimed to investigate the food effect on the pharmacokinetics (PK) of the recently developed nano-crystallized megestrol acetate (NCMA), using a model-based approach. Data were obtained from an NCMA PK study consisting of a single dose in fasting (39 individuals) and fed conditions (40 individuals). Plasma concentrations were measured up to 120 hr after dosing. With the incorporation of body-weight via allometry, NONMEM 7.3 was used to develop a PK model, which was then used to simulate an optimal fasting dose yielding an area under concentration (AUC) and maximum concentration (Cmax ) of NCMA close to those obtained with the fed dose. NCMA concentrations were best characterized by a two-compartment model with first-order absorption linked to a recycling compartment to account for the multiple concentration peaks observed. Food increased bioavailability 2.2 times and decreased the absorption rate constant 0.58 times. Recycling event times were estimated to be 3.56, 7.99 and 24.0 hr. The optimal fast dose was 2.0 times higher than the fed dose, and the resulting difference in drug exposure between the fasting and fed dose was 7.5%. This work suggests that the PK model developed can be applied to an optimal dosage regimen design for NCMA treatment.


Assuntos
Estimulantes do Apetite/administração & dosagem , Estimulantes do Apetite/farmacocinética , Interações Alimento-Droga , Acetato de Megestrol/administração & dosagem , Acetato de Megestrol/farmacocinética , Modelos Biológicos , Administração Oral , Adulto , Estimulantes do Apetite/uso terapêutico , Disponibilidade Biológica , Caquexia/tratamento farmacológico , Estudos Cross-Over , Sistemas de Liberação de Medicamentos/métodos , Cálculos da Dosagem de Medicamento , Ingestão de Alimentos , Jejum , Voluntários Saudáveis , Humanos , Masculino , Acetato de Megestrol/uso terapêutico , Nanopartículas , República da Coreia , Adulto Jovem
14.
Taiwan J Obstet Gynecol ; 55(3): 309-13, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27343306

RESUMO

OBJECTIVE: The aim of this study was to investigate the clinical and laboratory features of patients with the incidental diagnosis of endometrial adenocarcinoma (EC) during infertility work-up, with special attention given to treatment approaches, recurrence rate, and fertility outcome. MATERIAL AND METHODS: The medical records of 577 patients who were diagnosed with EC and treated between 2007 and 2013 were included in the study. Out of 577 EC patients, 5.1% (n = 30) were ≤ 40 years of age. However, 10 patients had a history of infertility and had been diagnosed during evaluation for infertility. Patients' clinical and laboratory data were reviewed retrospectively. RESULTS: The mean age at diagnosis was 34.3 ± 4.5 years and the mean duration of infertility was 5.1 ± 4.7 years. Immediate staging surgery was performed on three patients. The others were treated with oral megestrol acetate and/or a levonorgestrel-containing intrauterine device (IUD) for 6 months. The mean duration of postoperative or postdiagnostic follow-up was 44.7 ± 25.9 months. The disease persistence and recurrence rates were 11.1% and 22.2%, respectively. Two patients achieved pregnancy naturally or by assisted reproductive technology (ART) trial. CONCLUSION: The investigation of patients during infertility work-up provides an opportunity to evaluate the endometrium and its malignancies in young women, when the disease is in its early stage and symptom free. The standard surgical treatment for early-stage EC is total hysterectomy with bilateral salpingo-oophorectomy. However, conservative management of early stage EC with progestational drugs, especially in young patients who wish to preserve their fertility, is acceptable with the possibility of future pregnancies.


Assuntos
Adenocarcinoma/patologia , Adenocarcinoma/terapia , Neoplasias do Endométrio/patologia , Neoplasias do Endométrio/terapia , Infertilidade Feminina/complicações , Recidiva Local de Neoplasia/patologia , Adenocarcinoma/complicações , Adulto , Antineoplásicos Hormonais/uso terapêutico , Neoplasias do Endométrio/complicações , Feminino , Preservação da Fertilidade , Humanos , Achados Incidentais , Dispositivos Intrauterinos Medicados , Levanogestrel/administração & dosagem , Acetato de Megestrol/uso terapêutico , Gradação de Tumores , Estadiamento de Neoplasias , Gravidez , Taxa de Gravidez , Estudos Retrospectivos , Turquia
15.
Clin Breast Cancer ; 16(3): 188-95, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-26971303

RESUMO

BACKGROUND: We conducted a review of randomized trials to compare the overall survival (OS) with fulvestrant 500 mg versus alternative treatment for estrogen receptor-positive advanced breast cancer following endocrine therapy failure. MATERIALS AND METHODS: Hazard ratios (HRs) were obtained by modeling OS data with the Weibull distribution. A fixed-effect Bayesian network meta-analysis was conducted. The evidence network included anastrozole 1 mg, letrozole 2.5 mg, fulvestrant 250 mg, exemestane 25 mg, megestrol acetate 40 mg, and everolimus 10 mg plus exemestane 25 mg as comparators. Post-antiestrogen and post-aromatase inhibitor subgroup networks were analyzed. RESULTS: In the overall analysis, the HRs suggested improved OS for fulvestrant 500 mg versus fulvestrant 250 mg and megestrol acetate 40 mg, and numerically favorable differences with fulvestrant 500 mg versus other comparators. In the antiestrogen subgroup, the HRs suggested improved OS for fulvestrant 500 mg versus fulvestrant 250 mg and megestrol acetate 40 mg; numerical differences in the HRs were seen versus anastrozole 1 mg and letrozole 2.5 mg. In the aromatase inhibitor subgroup, the HRs for OS numerically favored fulvestrant 500 mg versus fulvestrant 250 mg and exemestane 25 mg. CONCLUSION: Acknowledging the limitations of the present network meta-analysis, these findings suggest that fulvestrant 500 mg might provide improved OS versus fulvestrant 250 mg and megestrol acetate 40 mg for treatment of estrogen receptor-positive ABC following endocrine therapy failure. Although OS efficacy versus everolimus 10 mg plus exemestane 25 mg (for overall evidence network), anastrozole 1 mg, exemestane 25 mg, and letrozole 2.5 mg is numerically favorable, additional studies are required to draw formal conclusions.


Assuntos
Antineoplásicos Hormonais/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Estradiol/análogos & derivados , Anastrozol , Androstadienos/uso terapêutico , Antineoplásicos/uso terapêutico , Inibidores da Aromatase/uso terapêutico , Neoplasias da Mama/mortalidade , Intervalo Livre de Doença , Relação Dose-Resposta a Droga , Estradiol/administração & dosagem , Estradiol/uso terapêutico , Everolimo/uso terapêutico , Feminino , Fulvestranto , Humanos , Letrozol , Acetato de Megestrol/uso terapêutico , Meta-Análise em Rede , Nitrilos/uso terapêutico , Pós-Menopausa , Receptores Estrogênicos/biossíntese , Resultado do Tratamento , Triazóis/uso terapêutico
16.
Vet Ophthalmol ; 19 Suppl 1: 86-90, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26938779

RESUMO

OBJECTIVE: To evaluate a compounded ophthalmic formulation of 0.5% megestrol acetate to treat eosinophilic keratitis in cats. STUDY DESIGN: Prospective study. ANIMALS STUDIED: Seventeen client owned cats with eosinophilic keratitis in one or both eyes. METHODS: Eosinophilic keratitis was confirmed by cytology. At each visit, fluorescein staining and photography were performed. Cats were initially treated q 8-12 h with 0.5% megestrol acetate in an aqueous base. Serum glucose was measured at the first or second reexamination. RESULTS: Fifteen of 17 (88%) cats had a positive response to treatment, with 6 of 17 (35%) having complete resolution at the first reexamination (2-4 weeks). Two of 17 (12%) cats did not respond to treatment. Most cats required a treatment frequency of once daily to once weekly to maintain remission of disease. No ocular irritation or systemic side effects were noted in any cat. CONCLUSIONS AND CLINICAL RELEVANCE: The use of an ophthalmic formulation of 0.5% megestrol acetate is a viable option for treating feline eosinophilic keratitis.


Assuntos
Doenças do Gato/tratamento farmacológico , Ceratite/veterinária , Acetato de Megestrol/uso terapêutico , Soluções Oftálmicas/uso terapêutico , Progestinas/uso terapêutico , Administração Oftálmica , Animais , Doenças do Gato/patologia , Gatos , Eosinófilos , Feminino , Ceratite/tratamento farmacológico , Ceratite/patologia , Masculino , Acetato de Megestrol/administração & dosagem , Acetato de Megestrol/efeitos adversos , Soluções Oftálmicas/efeitos adversos , Progestinas/efeitos adversos , Estudos Prospectivos
17.
J Ren Nutr ; 26(3): 168-76, 2016 05.
Artigo em Inglês | MEDLINE | ID: mdl-26776251

RESUMO

OBJECTIVE: To assess the efficacy and safety of oral megestrol acetate (MA) in the management of protein-energy wasting in patients with chronic kidney disease (CKD). DESIGN: A systematic review of English published literature from 1970 until April 1, 2014. SUBJECTS: All adult patients with CKD including both dialysis and non-dialysis-dependent. INTERVENTION: Oral MA. MAIN OUTCOME MEASURE: Efficacy outcomes included changes in body weight, serum albumin, and appetite. Safety outcomes examined included adverse events (AEs) and deaths. RESULTS: A total of 9 studies met the inclusion criteria. No data on MA in non-dialysis CKD patients were available. Statistically significant increases in body weight (range 1.5-5 kg) were reported in 6 trials. Statistically significant increases in albumin (range of 0.22 g/dL-0.52 g/dL) were observed in 5 trials. Improved appetite was observed in 7 trials. All trials were limited by small sample sizes (range 9-32 subjects), short duration (range 8-24 weeks), a high degree of bias, and absence of clinical outcomes such as quality of life or hospitalizations. Forty-seven AEs were reported and included overhydration/excessive fluid gain, diarrhea, hyperglycemia, excessive weight gain, suppressed cortisol levels, thrombophlebitis, nausea/vomiting, confusion/hallucinations, vaginal bleeding, headache/dizziness, and elevated lactate dehydrogenase. There were 26 discontinuations due to death. CONCLUSION: The current evidence for treatment with MA in patients receiving dialysis is sparse with few high-quality trials. The safety of using MA beyond 24 weeks is unknown, and use of MA is associated with significant AEs. At this time, oral MA should be used with significant caution, and only when other treatment options are unavailable.


Assuntos
Estimulantes do Apetite , Acetato de Megestrol/efeitos adversos , Acetato de Megestrol/uso terapêutico , Insuficiência Renal Crônica/complicações , Síndrome de Emaciação/tratamento farmacológico , Apetite , Peso Corporal , Humanos , Estado Nutricional , Qualidade de Vida , Diálise Renal , Insuficiência Renal Crônica/fisiopatologia , Albumina Sérica/análise , Resultado do Tratamento , Síndrome de Emaciação/etiologia , Ganho de Peso
18.
J Ren Care ; 42(1): 53-9, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26537025

RESUMO

BACKGROUND: Various populations are affected by chronic kidney disease (CKD), and a low dose appetite stimulant megestrol acetate (MA) is sometimes recommended in patients with CKD to ameliorate protein-energy wasting (PEW). Patients with CKD are at greater risk of developing PEW since the progression of their disease can cause decreased nutrient intake, catabolic effects, systemic inflammation and metabolic changes. Providers can detect PEW in CKD by identifying low serum levels ≤3.8 g/dl of albumin, <30 mg/dl of transthyretin, or <100 mg/dl of cholesterol. Other characteristics include BMI <22 kg/m(2) (for ≤65 years), unintentional weight loss of ≥5% in three months or ≥10% in six months, body fat percentage <10%, with muscle wasting of a reduction of ≥5% in three months or ≥10% in six months of muscle mass. METHOD: A review of research was completed and data collected from small population-based retrospective studies to determine the effect of MA. RESULTS: Clinical trials demonstrated the effectiveness of MA by showing increases in BMI up to 9%, albumin levels up to 1.1 g/dl, with reported protein and energy intake increases from 27% to 42%. There are potential adverse effects of using MA in CKD. CONCLUSION: After reviewing the available literature, the benefits of using MA should be evaluated against the potential side effects. For further examination of MA's potential benefits, long-term, prospective, large clinical trials should be carried out.


Assuntos
Estimulantes do Apetite/uso terapêutico , Acetato de Megestrol/uso terapêutico , Desnutrição Proteico-Calórica/tratamento farmacológico , Insuficiência Renal Crônica/complicações , Síndrome de Emaciação/tratamento farmacológico , Estimulantes do Apetite/efeitos adversos , Humanos , Acetato de Megestrol/efeitos adversos , Desnutrição Proteico-Calórica/etiologia , Insuficiência Renal Crônica/tratamento farmacológico , Síndrome de Emaciação/etiologia
19.
Diabetes Res Clin Pract ; 110(3): 285-90, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26515910

RESUMO

AIMS: We aimed to examine whether morphine treatment is associated with type 2 diabetes mellitus (T2DM) in female breast cancer patients. METHODS: We conducted a retrospective cohort analysis of the Longitudinal Health Insurance Database for Catastrophic Illness Patients in Taiwan. A total of 31,112 women with breast cancer without T2DM history during the period 2000-2005 were identified, divided into morphine and non-morphine users (8071 and 23,041 patients, respectively), and the hazard ratios of newly diagnosed T2DM during the period 2005-2010 were calculated. We used a Cox proportional hazard model with time-dependent exposure covariates to estimate the risk of T2DM. The dosage of morphine was counted as defined daily dose and its effect was assessed by multivariable Cox proportional hazard regression controlling age, Charlson comorbidity index, outpatient department visits, antipsychotics, and breast cancer drugs. RESULTS: Morphine users were 1.24 times more likely to suffer from T2DM than non-morphine users (95% CI=1.04-1.49). Risk increased slightly with the morphine dosage, in patients aged 35-49 years, and with tamoxifen, aromatase inhibitors, and antipsychotics treatment. CONCLUSIONS: The incidence of T2DM is associated with morphine treatment in female breast cancer patients. A higher risk was observed in patients aged 35-49 years using higher dose of morphine, and may be increased by tamoxifen and aromatase inhibitors.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Diabetes Mellitus Tipo 2/epidemiologia , Morfina/efeitos adversos , Adulto , Idoso , Inibidores da Aromatase/uso terapêutico , Feminino , Humanos , Incidência , Acetato de Megestrol/uso terapêutico , Pessoa de Meia-Idade , Morfina/uso terapêutico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Taiwan/epidemiologia , Tamoxifeno/uso terapêutico , Adulto Jovem
20.
Eur J Obstet Gynecol Reprod Biol ; 195: 61-6, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26476800

RESUMO

OBJECTIVE: Low-grade endometrial stromal sarcoma (LG-ESS) is a rare malignancy, often occurring before menopause. There is no consensus regarding its optimal management. Total hysterectomy and bilateral salpingo-oophorectomy precludes future fertility and may thus be undesirable by women wishing to maintain their reproductive potential. However, experience of fertility-sparing management in LG-ESS is very limited. In this paper, the disease outcome is presented in six young women with LG-ESS conservatively treated by combined hysteroscopic resection and hormonal therapy. STUDY DESIGN: From October 2009 to February 2013, at the Gynecologic Oncology Department of the National Cancer Institute of Naples, six women, with early-stage LG-ESS aged 18-40 years who desired childbearing and/or retaining their fertility, were enrolled into a pilot study of fertility-sparing management. Diagnosis of LG-ESS was made on specimens from hysteroscopic resection performed on a presumed benign lesion. All patients were planned to be treated with adjuvant megestrol acetate for two years. Hormonal therapy was started within 6 weeks from the hysteroscopic resection, with orally megestrol acetate at 40mg daily, increasing gradually according to patient's tolerance to the recommended total dose of 160mg daily. RESULTS: All patients were submitted to hysteroscopic resection in a one-step procedure. Five patients started megestrol acetate within 6 weeks from the hysteroscopic resection (one patient did not start hormonal therapy because of early pregnancy after the hysteroscopic resection). Hormonal therapy was well tolerated; one patient stopped megestrol acetate after 12 months because of self-supporting strong desire to conceive; the other four patients regularly completed the hormonal therapy. To date, all patients show no evidence of disease. CONCLUSIONS: Although fertility-sparing management is not the current standard of care for young women with early-stage LG-ESS, our preliminary data are promising. Larger series with a longer follow-up are needed to further assess safety and efficacy of combined hysteroscopic resection and hormonal therapy.


Assuntos
Antineoplásicos Hormonais/uso terapêutico , Neoplasias do Endométrio/terapia , Preservação da Fertilidade , Histeroscopia , Acetato de Megestrol/uso terapêutico , Taxa de Gravidez , Sarcoma/terapia , Útero/cirurgia , Adolescente , Adulto , Quimioterapia Adjuvante , Estudos de Coortes , Gerenciamento Clínico , Neoplasias do Endométrio/patologia , Feminino , Humanos , Gradação de Tumores , Estadiamento de Neoplasias , Tratamentos com Preservação do Órgão , Projetos Piloto , Gravidez , Sarcoma/patologia , Adulto Jovem
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