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Journal of Cachexia, Sarcopenia and... Oct 2023In cancer cachexia trials, measures of physical function are commonly used as endpoints. For drug trials to obtain regulatory approval, efficacy in physical function...
In cancer cachexia trials, measures of physical function are commonly used as endpoints. For drug trials to obtain regulatory approval, efficacy in physical function endpoints may be needed alongside other measures. However, it is not clear which physical function endpoints should be used. The aim of this systematic review was to assess the frequency and diversity of physical function endpoints in cancer cachexia trials. Following a comprehensive electronic literature search of MEDLINE, Embase and Cochrane (1990-2021), records were retrieved. Eligible trials met the following criteria: adults (≥18 years), controlled design, more than 40 participants, use of a cachexia intervention for more than 14 days and use of a physical function endpoint. Physical function measures were classified as an objective measure (hand grip strength [HGS], stair climb power [SCP], timed up and go [TUG] test, 6-min walking test [6MWT] and short physical performance battery [SPPB]), clinician assessment of function (Karnofsky Performance Status [KPS] or Eastern Cooperative Oncology Group-Performance Status [ECOG-PS]) or patient-reported outcomes (physical function subscale of the European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaires [EORTC QLQ-C30 or C15]). Data extraction was performed using Covidence and followed PRISMA guidance (PROSPERO registration: CRD42022276710). A total of 5975 potential studies were examined and 71 were eligible. Pharmacological interventions were assessed in 38 trials (54%). Of these, 11 (29%, n = 1184) examined megestrol and 5 (13%, n = 1928) examined anamorelin; nutritional interventions were assessed in 21 trials (30%); and exercise-based interventions were assessed in 6 trials (8%). The remaining six trials (8%) assessed multimodal interventions. Among the objective measures of physical function (assessed as primary or secondary endpoints), HGS was most commonly examined (33 trials, n = 5081) and demonstrated a statistically significant finding in 12 (36%) trials (n = 2091). The 6MWT was assessed in 12 trials (n = 1074) and was statistically significant in 4 (33%) trials (n = 403), whereas SCP, TUG and SPPB were each assessed in 3 trials. KPS was more commonly assessed than the newer ECOG-PS (16 vs. 9 trials), and patient-reported EORTC QLQ-C30 physical function was reported in 25 trials. HGS is the most commonly used physical function endpoint in cancer cachexia clinical trials. However, heterogeneity in study design, populations, intervention and endpoint selection make it difficult to comment on the optimal endpoint and how to measure this. We offer several recommendations/considerations to improve the design of future clinical trials in cancer cachexia.
Topics: Humans; Cachexia; Hand Strength; Neoplasms; Quality of Life; Research Design
PubMed: 37671529
DOI: 10.1002/jcsm.13321 -
Journal of Obstetrics and Gynaecology :... Jul 2022Endometrial cancer is the most common malignancy of the female genital tract. Approximately 25% of cases occur in premenopausal women, and up to 5% of cases occur in... (Review)
Review
Endometrial cancer is the most common malignancy of the female genital tract. Approximately 25% of cases occur in premenopausal women, and up to 5% of cases occur in women who are younger than 40 years old. The survival rate in these cases is 99%; therefore, uterine-sparing management could be considered under strict criteria selection and the strong desire of the woman to preserve uterus and fertility. Diagnosis should be performed after a hysteroscopic biopsy instead of dilatation and curettage. The highest remission rate was achieved after combining a hysteroscopic resection with hormonal therapy compared to single hormonal treatment. The most common regiments are the following progestins: megestrol acetate (MA) and medroxyprogesterone acetate (MPA) taken orally with a daily dosage of 160 mg-320 mg for MA and 250 mg-600 mg for MP. Evaluations at three and six months could be performed by office endometrial biopsy and/or hysteroscopic directed biopsy especially in the presence of levonorgestrel intrauterine system, and in cases of remission, either a pregnancy attempt or maintenance therapy should be considered. After childbearing, hysterectomy with bilateral salpingo-oophorectomy is recommended, whereas ovarian preservation could be considered depending on the patient's age and whether they fulfil the strict criteria selection.
Topics: Adult; Antineoplastic Agents, Hormonal; Endometrial Hyperplasia; Endometrial Neoplasms; Female; Fertility Preservation; Humans; Hysteroscopy; Levonorgestrel; Pregnancy; Uterus
PubMed: 34989284
DOI: 10.1080/01443615.2021.2006164 -
Gynecological Endocrinology : the... Dec 2023To investigate safety and effectiveness of NOMAC-E2 and levonorgestrel-containing COCs (COC) in users over 40. (Observational Study)
Observational Study
OBJECTIVE
To investigate safety and effectiveness of NOMAC-E2 and levonorgestrel-containing COCs (COC) in users over 40.
METHODS
In this large, observational study, new users of NOMAC-E2 and COC were recruited in Europe, Australia, and Latin America and followed-up questionnaires. Incidence of venous thromboembolism (VTE) was expressed as incidence rate (IR; events/10 women-years [WY]). Unintended pregnancy was expressed by the Pearl Index (PI; contraceptive failures/100 WY). Mood and weight changes were defined as mean changes in mood score and percentage of body weight.
RESULTS
Overall, 7,762 NOMAC-E2 and 6,059 COC users over 40 were followed-up. NOMAC-E2 showed no increased VTE risk compared to COC; confirmed events: 5 NOMAC-E2 (IR 5.9; 95% CI, 1.9-13.7) vs 4 COC (IR 5.9; 95% CI, 1.6-15.1). Unintended pregnancy did not differ substantially between cohorts; confirmed events: 4 NOMAC-E2 (PI 0.05; 95% CI, 0.01-0.13) vs 5 COC (PI 0.08; 95% CI, 0.03-0.18). No differential effect on mood and weight was observed between cohorts.
CONCLUSIONS
NOMAC-E2 can be considered a valid alternative to COC in perimenopausal women.
Topics: Pregnancy; Female; Humans; Contraceptives, Oral, Combined; Ethinyl Estradiol; Estradiol; Venous Thromboembolism; Megestrol; Norpregnadienes
PubMed: 36690019
DOI: 10.1080/09513590.2023.2166032 -
Cancers Jul 2023This study compared mirtazapine with megestrol in the management of cancer-related anorexia-cachexia syndrome in patients with advanced cancer. A randomized,...
Mirtazapine versus Megestrol in the Treatment of Anorexia-Cachexia Syndrome in Patients with Advanced Cancer: A Randomized, Double-Blind, Controlled Phase II Clinical Trial.
This study compared mirtazapine with megestrol in the management of cancer-related anorexia-cachexia syndrome in patients with advanced cancer. A randomized, double-blind, controlled clinical trial involving patients with advanced cancer and anorexia-cachexia syndrome was performed. Participants received mirtazapine 30 mg/day or megestrol 320 mg/day for eight weeks. The primary endpoint was the effect of mirtazapine on weight gain and the secondary endpoints were its effect on appetite, muscle strength, physical performance, body composition, adverse events, and medication adherence. Linear regression model with mixed effects was applied and a significance level of 5% was adopted. Fifty-two patients were randomized. Mean age was 65.8 ± 8.4 years. There was weight gain in 52% of the participants in the megestrol group and in 38% in the mirtazapine group after four weeks ( = 0.040). Appetite improved in 92% of the participants in the megestrol group and in 56% in the mirtazapine group after eight weeks ( = 0.007). In the sub-analysis by sex, women showed improvement in appetite ( < 0.001) and weight gain ( < 0.005) in the mirtazapine group, which was not observed in men. Mirtazapine appears to be inferior to megestrol in weight and appetite improvement. However, there may be a difference in the therapeutic response between sexes.
PubMed: 37509249
DOI: 10.3390/cancers15143588 -
Minerva Medica Feb 2021Primary surgery is effective in low-risk endometrial cancer (EC). However, in young women, this approach compromises fertility. Therefore, fertility-sparing management... (Review)
Review
INTRODUCTION
Primary surgery is effective in low-risk endometrial cancer (EC). However, in young women, this approach compromises fertility. Therefore, fertility-sparing management in the case of atypical endometrial hyperplasia, or grade 1 EC limited to the endometrium can be considered.
EVIDENCE ACQUISITION
We performed a literature review to identify studies involving women with EC or atypical hyperplasia who underwent fertility-sparing management. We conducted multiple bibliographic databases research from their inception to May 2020.
EVIDENCE SYNTHESIS
Oral therapy with medroxyprogesterone acetate and megestrol acetate is recommended based on extensive experience, although without consensus on dosages and treatment length. The pooled complete response rate, recurrence rate, and pregnancy rate of EC were 76.3%, 30.7% and 52.1%, respectively. Endometrial hyperplasia was associated with better outcomes. LNG-IUSs appears an alternative treatment, particularly in patients who do not tolerate oral therapy. In a randomized controlled trial, megestrol acetate plus metformin guaranteed an earlier complete response rate than megestrol acetate alone for endometrial hyperplasia. Hysteroscopic resection followed by progestogens is associated with a higher complete response rate, live birth rate, and lower recurrence rate than oral progestogens alone. Pooled complete response, recurrence, and live birth rates were 98.1%, 4.8% and 52.6%.
CONCLUSIONS
Fertility preservation appears feasible in young patients with grade 1 EC limited to the endometrium or atypical endometrial hyperplasia. Progestins are the mainstay of such management. The addition of Metformin and hysteroscopic resection seems to provide some improvements. However, fertility preservation is not the standard approach for staging and treatment, potentially worsening oncologic outcomes.
Topics: Administration, Oral; Drug Carriers; Endometrial Hyperplasia; Endometrial Neoplasms; Female; Fertility Preservation; Humans; Hysteroscopy; Levonorgestrel; Metformin; Progestins
PubMed: 33205638
DOI: 10.23736/S0026-4806.20.07072-X -
Nephrology Nursing Journal : Journal of... 2021Nutritional and metabolic abnormalities, or protein energy wasting, is a common complication of chronic kidney disease, leading to significant morbidity and mortality.... (Review)
Review
Nutritional and metabolic abnormalities, or protein energy wasting, is a common complication of chronic kidney disease, leading to significant morbidity and mortality. The cause of these abnormalities is multifactorial, and therefore, difficult to treat. The International Society of Renal Nutrition and Metabolism suggests appetite stimulants, including megestrol, dronabinol, mirtazapine, and cyproheptadine, as adjunctive treatment options in addition to parenteral or oral nutritional supplementation. This article reviews the evidence for use of these drugs as appetite stimulants and discusses their use in patients with chronic kidney disease.
Topics: Appetite Stimulants; Humans; Nutritional Status; Renal Dialysis; Renal Insufficiency, Chronic
PubMed: 34286938
DOI: No ID Found -
Cancers Oct 2023Granular cell tumors (GCT) represent 0.5% of all soft tissue sarcomas (STS), and when metastatic, they exhibit aggressive behavior and determine limited survival.... (Review)
Review
Granular cell tumors (GCT) represent 0.5% of all soft tissue sarcomas (STS), and when metastatic, they exhibit aggressive behavior and determine limited survival. Metastatic GCTs are relatively chemo-resistant; however, there is growing evidence of the benefit of using pazopanib and other targeted therapies in this histology. This is a review of the role of pazopanib and other targeted therapies in the treatment of GCTs, along with some insights on pathology and molecular biology described in GCTs. From 256 articles found in our search, 10 case-report articles met the inclusion criteria. Pazopanib was the most employed systemic therapy. The median reported time on therapy with pazopanib was seven months. Eight out of ten patients (80%) experienced disease control with pazopanib, while four out of ten (40%) patients achieved an objective RECIST response. Molecular studies suggested that antitumoral effects of pazopanib in GCT might be due to a loss-of-function of genes which consequently enhance signaling through several molecular pathways, such as SFKs, STAT5a/b, and PDGFR-β. Other reported targeted therapies for malignant GCTs included pazopanib in combination with crizotinib, which showed disease control for four months in one patient, and a PI3K inhibitor which achieved disease control for nine months in another patient. Dasatinib and megestrol were ineffective in two other different patients. Pazopanib has been demonstrated to be active in advanced GCTs and may be considered as a preferable treatment option.
PubMed: 37958362
DOI: 10.3390/cancers15215187 -
Medicina Clinica Mar 2022
Topics: Adolescent; Adrenal Insufficiency; Child; Humans; Hydrocortisone; Megestrol; Megestrol Acetate
PubMed: 34074479
DOI: 10.1016/j.medcli.2021.04.019 -
The American Journal of Geriatric... Jun 2020To analyze the risk of megestrol, a glucocorticoid and progesterone receptor agonist used to enhance appetite, on the development of a new psychiatric diagnosis. (Comparative Study)
Comparative Study
OBJECTIVE
To analyze the risk of megestrol, a glucocorticoid and progesterone receptor agonist used to enhance appetite, on the development of a new psychiatric diagnosis.
DESIGN AND PARTICIPANTS
Deidentified data of megestrol (n = 706) and propensity score-matched comparison (age, gender, and body mass index) patients (n = 2,118) from January 1, 2001 to June 30, 2018 were obtained from the UT Southwestern patient database. Data were analyzed using a series of conditional binary logistic regressions controlling for comorbidities, pre-existing psychiatric disorders, and number of patient encounters.
SETTING
A large academic medical center database of megestrol-treated patients and matched comparison patients was used.
MEASUREMENTS AND RESULTS
The regression model showed that megestrol was significantly associated with developing a new psychiatric diagnosis (B = 1.28, Wald χ = 83.12, odds ratio [OR] = 3.60, p <0.001). In subgroup analyses, development of cognitive (B = 2.42, Wald χ = 16.09, OR = 11.30, p <0.001), mood (B = 1.31, Wald χ = 40.38, OR = 3.70, p <0.001), and anxiety (B = 1.72, Wald χ = 45.28, OR = 5.60, p <0.001) disorders were also associated with megestrol use.
CONCLUSIONS
Patients taking megestrol were significantly more likely to develop a new psychiatric diagnosis than comparison patients. Highest risks were associated with the development of cognitive diagnoses. The findings suggest that megestrol, like other glucocorticoid agonists, is associated with an increased risk of developing a psychiatric disorder. This risk should be considered when determining the risk-to-benefit ratio of megestrol use in patients.
Topics: Aged; Anxiety Disorders; Comorbidity; Databases, Factual; Female; Glucocorticoids; Humans; Logistic Models; Male; Megestrol; Middle Aged; Psychoses, Substance-Induced; Risk Factors; Texas
PubMed: 32037291
DOI: 10.1016/j.jagp.2020.01.003 -
BMC Women's Health May 2022To evaluate the effects of a combined oral contraceptive containing 1.5 mg 17b-estradiol (E2) and 2.5 mg nomegestrol acetate (NOMAC) or 2 mg/daily dienogest (DNG)... (Randomized Controlled Trial)
Randomized Controlled Trial
Randomized study on the effectiveness of nomegestrol acetate plus 17β-estradiol oral contraceptive versus dienogest oral pill in women with suspected endometriosis‑associated chronic pelvic pain.
BACKGROUND
To evaluate the effects of a combined oral contraceptive containing 1.5 mg 17b-estradiol (E2) and 2.5 mg nomegestrol acetate (NOMAC) or 2 mg/daily dienogest (DNG) oral progestin on endometriosis-associated chronic pelvic pain (CPP) and on the quality of life (QoL) and sexual function, by a randomized study design.
METHODS
The E2/NOMAC group and DNG group included 99 and 98 women, respectively. The levels of CPP were measured by the visual analogic scale (VAS). The QoL scores were investigated by the Short Form-36 questionnaire (SF-36). Finally, sexual function was studied using the Female Sexual Function Index (FSFI), while sexual distress was studied by the Female Sexual Distress Scale (FSDS). The study had 3, 6 and 12-month follow-ups.
RESULTS
The intra-group analysis showed an improvement of the VAS score from baseline to the 12-month follow-up in the women of both groups (p < 0.001). The inter-group comparison showed a similar improvement of CPP (p = 0.06). Women on DNG had better SF-36 somatic (p < 0.01) and FSFI scores (p < 0.006) than women on E2/NOMAC at the 6- and 12-month follow-ups.
CONCLUSIONS
The results support the efficacy of both hormonal treatments, even if DNG was more effective than E2/NOMAC in a limited intergroup comparison.
Topics: Chronic Pain; Contraceptives, Oral, Combined; Endometriosis; Estradiol; Female; Humans; Male; Megestrol; Nandrolone; Norpregnadienes; Pelvic Pain; Quality of Life
PubMed: 35538479
DOI: 10.1186/s12905-022-01737-7