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The effects of megestrol acetate on nutrition, inflammation and quality of life in elderly haemodialysis patients.
Zheng, Z, Chen, J, He, D, Xu, Y, Chen, L, Zhang, T
International urology and nephrology. 2019;(9):1631-1638
Abstract
PURPOSE Malnutrition, inflammation and poor quality of life are prevalent among elderly haemodialysis patients. Megestrol acetate (MA) is a synthetic progestin that is widely used to increase appetite and weight in various clinical settings. MA has been indicated to be effective in improving quality of life in patients with cancers. The aim of the present study was to evaluate the efficacy and safety of MA in treating malnourished elderly haemodialysis patients. METHODS A randomized controlled study involving 46 hypoalbuminemia haemodialysis patients aged 70 years or older was conducted. The patients in MA-treated group (n = 23) took 160 mg of MA daily, while those in control group (n = 23) were enrolled without any intervention. Anthropometric parameters and laboratory results, including height, dry weight, body mass index, and modified subjective global assessment score as well as serum albumin, triglyceride, total cholesterol, hsCRP, IL-1b and IL-6 concentrations were measured in all patients before and after the intervention. Health-related quality of life was also evaluated using the KDQOL-SF 1.3. RESULTS In the MA-treated group, a total of 18 patients finished the therapy over a 3-month period. Appetite was reported as improved by 15 patients, and a statistically significant increase was observed in dry weight (53.36 ± 6.15 vs. 54.24 ± 6.32, P < 0.01) and serum albumin concentration (29.05 ± 3.91 vs. 37.67 ± 4.88, P < 0.01) in the MA-treated group compared to those of the control group. The quality of life in both the physical domain (46.73 ± 18.17 vs. 63.37 ± 22.35, P < 0.01) and the mental domain (50.28 ± 20.36 vs. 68.02 ± 25.48, P < 0.01) was also improved in the same group. There was no significant change in the inflammatory marker concentrations after the intervention. No serious or unexpected adverse events were observed except that one patient who withdrew due to excessive fluid gain between haemodialysis sessions. CONCLUSION Our data suggest that MA can be effective in improving nutritional status and quality of life by increasing appetite in elderly haemodialysis patients with acceptable side effects; however, MA might not ameliorate inflammation.
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A randomized, double-blind, placebo-controlled clinical trial of megestrol acetate as an appetite stimulant in children with weight loss due to cancer and/or cancer therapy.
Cuvelier, GD, Baker, TJ, Peddie, EF, Casey, LM, Lambert, PJ, Distefano, DS, Wardle, MG, Mychajlunow, BA, Romanick, MA, Dix, DB, et al
Pediatric blood & cancer. 2014;(4):672-9
Abstract
BACKGROUND Megestrol acetate (MA) is an appetite stimulant with efficacy in promoting weight gain in adults with cancer-associated anorexia-cachexia. Studies documenting MA efficacy in children, however, are limited. We present the first randomized, double-blind, placebo-controlled clinical trial of MA versus placebo in children with cancer and weight loss. METHODS Subjects <18 years of age with weight loss (minimum 5% from highest previous weight; or %ideal body weight <90%) due to cancer and/or cancer therapy were randomized to either MA (7.5 mg/kg/day) or placebo for a planned study duration of 90 days. Primary outcome was the difference between groups in mean percent weight change from beginning to end of the study period. Secondary outcomes included effects on anthropometrics, body composition, need for tube feeding or parenteral nutrition, and toxicities. RESULTS Twenty-six patients were randomly assigned (13 MA, 13 placebo). The MA group experienced a mean weight gain of +19.7% compared to a mean weight loss of -1.2% in the placebo group, for a difference of +20.9% (95%CI: +11.3% to +30.5%, P = 0.003) in favor of MA over placebo. MA subjects experienced significant increases in weight for age z-scores, body mass index z-scores, and mid upper arm circumference compared to placebo. DXA scanning suggested disproportionate increases in fat accrual. Adrenal suppression was the main toxicity of MA. CONCLUSION In children with high-risk malignancies, MA resulted in significant increases in mean percent weight change compared to placebo. Further studies of MA should be pursued to better delineate the effect on nutritional status.
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Comparison of three different treatment modalities in the management of cancer cachexia.
Kanat, O, Cubukcu, E, Avci, N, Budak, F, Ercan, I, Canhoroz, M, Olmez, F
Tumori. 2013;(2):229-33
Abstract
AIMS AND BACKGROUND The optimal treatment of cancer cachexia remains unknown. In this study, we compared the efficacy of three different treatment modalities in the management of cancer cachexia. METHODS Sixty-two assessable cachectic cancer patients were randomized to one of the following three arms: 1) megesterol acetate (MA) plus meloxicam (n = 23); 2) MA plus meloxicam plus oral eicosapentaenoic acid (EPA)-enriched nutritional supplement (n = 21); or 3) meloxicam plus oral EPA-enriched nutritional supplement (n = 18). Treatment duration was 3 months. RESULTS The treatment arms were well balanced at baseline. The primary efficacy (body weight and lean body mass) and secondary efficacy (body mass index, quality of life, and serum levels of IL-6 and TNF-α) parameters improved after treatment in all three arms. There were no statistically significant differences between treatment groups in the mean percentage changes in all efficacy parameters from baseline to end of study. CONCLUSIONS MA plus meloxicam or EPA supplement plus meloxicam may be effective treatment options in the management of cancer cachexia. The combined use of these agents does not provide further advantages.
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Randomized phase III clinical trial of a combined treatment with carnitine + celecoxib ± megestrol acetate for patients with cancer-related anorexia/cachexia syndrome.
Madeddu, C, Dessì, M, Panzone, F, Serpe, R, Antoni, G, Cau, MC, Montaldo, L, Mela, Q, Mura, M, Astara, G, et al
Clinical nutrition (Edinburgh, Scotland). 2012;(2):176-82
Abstract
BACKGROUND & AIMS A phase III, randomized non-inferiority study was carried out to compare a two-drug combination (including nutraceuticals, i.e. antioxidants) with carnitine + celecoxib ± megestrol acetate for the treatment of cancer-related anorexia/cachexia syndrome (CACS): the primary endpoints were increase of lean body mass (LBM) and improvement of total daily physical activity. Secondary endpoint was: increase of physical performance tested by grip strength and 6-min walk test. METHODS Sixty eligible patients were randomly assigned to: arm 1, L-carnitine 4 g/day + Celecoxib 300 mg/day or arm 2, L-carnitine 4 g/day + celecoxib 300 mg/day + megestrol acetate 320 mg/day, all orally. All patients received as basic treatment polyphenols 300 mg/day, lipoic acid 300 mg/day, carbocysteine 2.7 g/day, Vitamin E, A, C. Treatment duration was 4 months. Planned sample size was 60 patients. RESULTS The results did not show a significant difference between tre atment arms in both primary and secondary endpoints. Analysis of changes from baseline showed that LBM (by dual-energy X-ray absorptiometry and by L3 computed tomography) increased significantly in both arms as well as physical performance assessed by 6MWT. Toxicity was quite negligible and comparable between arms. CONCLUSIONS The results of the present study showed a non-inferiority of arm 1 (two-drug combination) vs arm 2 (two-drug combination + megestrol acetate). Therefore, this simple, feasible, effective, safe, low cost with favorable cost-benefit profile, two-drug approach could be suggested in the clinical practice to implement CACS treatment.
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Influence of megestrol acetate on nutrition, inflammation and quality of life in dialysis patients.
Gołębiewska, JE, Lichodziejewska-Niemierko, M, Aleksandrowicz-Wrona, E, Majkowicz, M, Lysiak-Szydłowska, W, Rutkowski, B
International urology and nephrology. 2012;(4):1211-22
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Abstract
AIM: Malnutrition is a common clinical problem in dialysis patients. The objective of this study was to evaluate the efficacy and safety of megestrol acetate in malnourished dialysis patients. Thirty-two hypoalbuminemic dialysis patients took 160 mg of megestrol acetate daily for up to 6 months. METHODS We measured height, dry weight, BMI, modified Subjective Global Assessment (SGA) score, and serum albumin, triglycerides, total cholesterol, hsCRP, IL-1β and IL-6 concentrations. We used validated questionnaires to evaluate selected dimensions of the quality of life. RESULTS Only 12 patients completed the study. All patients reported improved appetite, and there were concurrent statistically significant increases in weight, BMI, SGA and albumin concentration (P < 0.05). For the 12 patients who completed 6 months of treatment the increase in these parameters was from 63.26 ± 13.04 to 65.58 ± 12.53 kg, from 23.5 ± 3.8 to 24.66 ± 4.23 kg/m(2), from 5.16 ± 0.94 to 6.16 ± 0.72 points, and from 36.45 ± 1.82 to 40.33 ± 2.71 g/l, respectively. However, there were no significant changes in the levels of inflammatory markers and in quality of life. Side effects included overhydration, excessive weight gain and hyperglycaemia. CONCLUSION Megestrol acetate may be effective in reversing poor appetite in carefully selected maintenance dialysis patients, but it might not reduce inflammation or improve the quality of life. Because of the potential side effects, close monitoring is essential.
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Report of a pilot, double-blind, placebo-controlled study of megestrol acetate in elderly dialysis patients with cachexia.
Yeh, SS, Marandi, M, Thode, HC, Levine, DM, Parker, T, Dixon, T, Schuster, MW
Journal of renal nutrition : the official journal of the Council on Renal Nutrition of the National Kidney Foundation. 2010;(1):52-62
Abstract
OBJECTIVE We examined the effects of megestrol acetate versus placebo and progressive resistance physical exercise on weight, lean muscle mass, quality of life, ability to exercise, proinflammatory cytokines, and anti-inflammatory cytokines, and their correlations with one another. DESIGN We organized a prospective 20-week, randomized, double-blind, placebo-controlled pilot trial of hemodialysis patients. SETTING This study took place at the Outpatient Unit of the Northport Veteran Affairs Medical Center. SUBJECTS We studied nine male hemodialysis patients who had two or more of the following: albumin level <4.0 g/dL, total cholesterol <150 mg/dL, protein catabolic rate <0.8 g/kg/day, and predialysis serum urea nitrogen <60 mg/dL. Their ages were 50 to 83 years. Two were diabetic, and seven were nondiabetic. INTERVENTIONS Interventions included megestrol acetate (MA) or placebo 800 mg oral daily for 20 weeks, along with weight resistance physical therapy with weights twice a week before dialysis. Patients were followed prospectively for an additional 4 weeks. MAIN OUTCOME MEASUREMENTS Weight, body composition, activities of daily living, ability to exercise, and plasma cytokine levels were measured. RESULTS At 24 weeks, the MA group had a statistically significant weight gain (11.1-pound increase vs. 1.5-pound decrease for the placebo group, P = .018), body fat gain (6.2-pound increase vs. a 0.4-pound decrease for the placebo group, P = .044) and fat-free mass gain (5-pound increase vs. a 1.2-pound decrease in the placebo group). The MA group also had a greater tendency toward increased appetite and sense of well-being. The MA group showed a greater improvement in ability to exercise (mean change in rate of perceived exertion (RPE), 4.7) vs. the placebo group (mean change in RPE vs. 0.5, P = .02). Elevated cytokine levels were evident at baseline in both groups. In all patients, increases in weight, fat-free mass, sense of well-being, appetite, and ability to exercise were negatively correlated with tumor necrosis factor receptor subunit p75 (P < .05). There was a trend toward all of these parameters to be negatively correlated with tumor necrosis factor receptor subunit p55, although only sense of well-being was statistically significant (P < .05). CONCLUSION In a pilot trial in dialysis patients, MA showed significant benefits in improving weight and ability to exercise. Cytokine changes were correlated with weight gains and increases in fat-free mass.
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Effect of megestrol acetate on serum albumin level in malnourished dialysis patients.
Monfared, A, Heidarzadeh, A, Ghaffari, M, Akbarpour, M
Journal of renal nutrition : the official journal of the Council on Renal Nutrition of the National Kidney Foundation. 2009;(2):167-71
Abstract
OBJECTIVE Malnutrition is a common problem in dialysis patients, and may affect up to one third of patients. It is associated with high mortality and morbidity. Although a number of studies were performed to determine effective treatment, there is no proven medication for this condition. This study aimed to evaluate the effect of megestrol acetate (MA) on serum albumin levels in malnourished dialysis patients. DESIGN This was a randomized, controlled clinical trial. SETTING The setting, a dialysis center at Razi Hospital, Rasht, Iran, provides services to dialysis patients. PATIENTS Twenty-two malnourished dialysis patients with persistent hypoalbuminemia (albumin, <3.5 g/dL for 2 months) participated, and were randomly assigned to either an experimental group or a control group. INTERVENTION The experimental group was treated with MA, 40 mg twice daily, over 2 months, and was compared with the control group. The collected data were analyzed using SPSS (version 10; Chicago, IL). RESULTS After 2 months, the mean (+/-SD) serum albumin level in the experimental group rose from 3.31 +/- 0.31 g/dL to 4.41 +/- 0.31 g/dL, but in the control group, it declined, from 3.35 +/- 0.21 to 3.02 +/- 0.48 g/dL. The difference between the two groups was significant (P = .002). CONCLUSION At a dose of 40 mg twice a day, MA safely increased serum albumin in malnourished dialysis patients.
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Effects of muscle strength training and megestrol acetate on strength, muscle mass, and function in frail older people.
Sullivan, DH, Roberson, PK, Smith, ES, Price, JA, Bopp, MM
Journal of the American Geriatrics Society. 2007;(1):20-8
Abstract
OBJECTIVES To determine the independent and combined effects of progressive resistance muscle strength training (PRMST) and megestrol acetate (MA) on strength, muscle mass, and function in older recuperative care patients. DESIGN Double-blind, randomized, controlled intervention using a two-by-two factorial design and conducted between 1999 and 2001. SETTING University-affiliated Department of Veterans Affairs hospital. PARTICIPANTS Twenty-nine patients (mean age 79.4 +/- 7.4, 90% white) aged 65 and older and had recent functional decline. INTERVENTIONS After randomization to one of four treatment groups (low-resistance exercises plus 800 mg per day of MA or a placebo or high-intensity PRMST plus 800 mg/d of MA or placebo), subjects received training and the drug or placebo for 12 weeks. MEASUREMENTS Change in muscle strength, mid-thigh muscle area, and aggregate functional performance score as assessed using analysis of covariance. RESULTS Five subjects withdrew from the study before its completion. Based on intent-to-treat analyses, subjects who received high-intensity PRMST and placebo experienced the greatest strength gains. The addition of MA was associated with worse outcomes than with high-intensity exercise training alone, especially with regard to the leg exercises. Post hoc analysis demonstrated that subjects who received high-intensity PRMST and placebo experienced significantly greater percentage increases in leg strength than subjects in either of the MA treatment groups (P<.05 for each comparison). There was also a significant negative effect of MA on physical function. In general, subjects who received MA experienced a deterioration in aggregate physical function scores, whereas the remaining subjects improved (-0.80+/-0.40 vs 0.48+/-0.41, P=.04). There was not a significant interaction between exercise and MA for any outcome. CONCLUSION High-intensity PRMST is a safe and well-tolerated exercise regimen for frail elderly patients. The addition of MA appears to blunt the beneficial effects of PRMST, resulting in less muscle strength and functional performance gains.
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The effects of megestrol acetate suspension for elderly patients with reduced appetite after hospitalization: a phase II randomized clinical trial.
Reuben, DB, Hirsch, SH, Zhou, K, Greendale, GA
Journal of the American Geriatrics Society. 2005;(6):970-5
Abstract
OBJECTIVES To provide preliminary evidence on the effectiveness and optimal dosage of megestrol acetate for older persons with impaired appetite after hospitalization. DESIGN Randomized clinical trial. SETTING Acute care hospital. PARTICIPANTS Forty-seven older persons (mean age 83) who were recently discharged from an acute care hospital and had fair or poor appetite. INTERVENTION Participants were randomized to placebo or megestrol acetate suspension 200 mg, 400 mg, or 800 mg daily for 9 weeks. MEASUREMENTS Appetite, health-related quality of life, and adverse effects were measured at baseline and 20, 42, and 63 days. Serum nutritional markers were measured at baseline and 20 and 63 days. RESULTS During the course of the study, there were no significant differences between treatment groups on any of the appetite questions, although participants in the 400-mg and 800-mg groups demonstrated significant improvement from baseline on some questions. At 20 days, prealbumin increased in a dose-response relationship across the four groups (by 0.4, 5.1, 7.5, and 9.0 mg/dL, respectively). Participants in the 400-mg and 800-mg groups demonstrated greater improvement in prealbumin levels at 20 days than those receiving placebo (P=.009 and P=.004, respectively) and those in the 400-mg group also demonstrated improvement at 63 days (P=.02). At 20 days, no participant taking placebo had a morning serum cortisol level less than 8 ng/mL (the lower limit of normal). In contrast, 33%, 70%, and 78% of those taking 200 mg, 400 mg and 800 mg, respectively, had values below this level; by 63 days, these percentages were 11%, 30%, 56%, and 37%, respectively. No patient reported clinical symptoms of adrenal insufficiency. Diarrhea developed in three subjects, and thromboembolism occurred in two receiving active treatment. CONCLUSION Megestrol acetate at doses of 400 mg and 800 mg increases prealbumin in recently hospitalized older persons. Cortisol suppression is common at higher doses and may be persistent. In this small study, the drug did not confer benefit on other nutritional or clinical outcomes.
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Risk factors relating blood markers of inflammation and nutritional status to survival in cachectic geriatric patients in a randomized clinical trial.
Yeh, SS, Hafner, A, Chang, CK, Levine, DM, Parker, TS, Schuster, MW
Journal of the American Geriatrics Society. 2004;(10):1708-12
Abstract
OBJECTIVES To evaluate the effect of proinflammatory cytokines, their receptors, and nutritional indicators (at baseline and after 12 weeks of megestrol acetate (MA) treatment) upon long-term survival in geriatric cachectic patients without active acute infections, inflammation, or cancer. DESIGN Randomized clinical trial with placebo or MA treatment for 12 weeks and then follow-up for more than 4 years. SETTING Veterans Affairs nursing home in Northport, New York. PARTICIPANTS Nursing home patients with weight loss of 5% of usual body weight over the previous 3 months or body weight 20% below ideal body weight. INTERVENTION Random assignment of placebo or MA oral suspension 800 mg/d to the eligible patients for 12 weeks. MEASUREMENTS White blood cell counts, prealbumin, plasma cytokine levels (or their receptors), including tumor necrosis factor receptor (TNFR), soluble subunits (TNFR-p55 and TNFR-p75), interleukin (IL)-6, soluble IL-2 receptor, and C-reactive protein at baseline and 12 weeks after treatment. RESULTS There was no difference in survival between the MA and placebo groups. Considering possible confounders, initial IL-6, initial TNFR-p75 levels, and final neutrophil percentage were associated with elevated mortality, whereas higher initial prealbumin, initial albumin, final prealbumin, final albumin, and final weight gain were associated with decreased death. CONCLUSION In geriatric weight-loss patients with cachexia, certain cytokines and nutritional indicators were effective in predicting long-term mortality, regardless of treatment with MA. Interventions to modify levels of these cytokines or their receptors and improvement in nutritional status by weight gain might be helpful in ameliorating undetected chronic inflammation and thus might prolong the survival of these nursing home residents.