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1.
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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2.
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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3.
Treatment of anorexia and malnutrition in peritoneal dialysis patients with megestrol acetate.
Costero, O, Bajo, MA, del Peso, G, Gil, F, Aguilera, A, Ros, S, Hevia, C, Selgas, R
Advances in peritoneal dialysis. Conference on Peritoneal Dialysis. 2004;:209-12
Abstract
Anorexia and malnutrition are common complications and powerful predictors of morbidity and mortality in peritoneal dialysis (PD) patients. Megestrol acetate (MA) is a progestogen that has been demonstrated to increase appetite and weight in patients with cancer or acquired immunodeficiency syndrome. To determine whether MA might benefit PD patients, we treated 32 patients with 160 mg MA daily. Treatment lasted a mean of 5.93 +/- 5.12 months (range: 1 - 23 months). In 68.8% of the patients, appetite improved. Weight gain was statistically significant starting in the third month (initial weight: 66.5 +/- 11.4 kg; weight at third month: 68 +/- 10.4 kg; p < 0.05). We observed a nonsignificant increase in serum albumin at the third treatment month (initial serum albumin: 3.44 +/- 0.27 g/L; serum albumin at third month: 3.54 +/- 0.27 g/L; p = 0.45). No side effects were observed. Our experience suggests that treatment with 160 mg MA daily in PD patients leads to an increase in appetite, serum albumin, and weight gain in most patients, with no negative side effects.
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4.
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.
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5.
An eicosapentaenoic acid supplement versus megestrol acetate versus both for patients with cancer-associated wasting: a North Central Cancer Treatment Group and National Cancer Institute of Canada collaborative effort.
Jatoi, A, Rowland, K, Loprinzi, CL, Sloan, JA, Dakhil, SR, MacDonald, N, Gagnon, B, Novotny, PJ, Mailliard, JA, Bushey, TI, et al
Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2004;(12):2469-76
Abstract
PURPOSE Studies suggest eicosapentaenoic acid (EPA), an omega-3 fatty acid, augments weight, appetite, and survival in cancer-associated wasting. This study determined whether an EPA supplement-administered alone or with megestrol acetate (MA)-was more effective than MA. PATIENTS AND METHODS Four hundred twenty-one assessable patients with cancer-associated wasting were randomly assigned to an EPA supplement 1.09 g administered bid plus placebo; MA liquid suspension 600 mg/d plus an isocaloric, isonitrogenous supplement administered twice a day; or both. Eligible patients reported a 5-lb, 2-month weight loss and/or intake of less than 20 calories/kg/d. RESULTS A smaller percentage taking the EPA supplement gained >or= 10% of baseline weight compared with those taking MA: 6% v 18%, respectively (P =.004). Combination therapy resulted in weight gain of >or= 10% in 11% of patients (P =.17 across all arms). The percentage of patients with appetite improvement (North Central Cancer Treatment Group Questionnaire) was not statistically different: 63%, 69%, and 66%, in EPA-, MA-, and combination-treated arms, respectively (P =.69). In contrast, 4-week Functional Assessment of Anorexia/Cachexia Therapy scores suggested MA-containing arms experienced superior appetite stimulation compared with the EPA arm, with scores of 40, 55, and 55 in EPA-, MA-, and combination-treated arms, respectively (P =.004). Survival was not significantly different among arms. Global quality of life was not significantly different among groups. With the exception of increased impotence in MA-treated patients, toxicity was comparable. CONCLUSION This EPA supplement, either alone or in combination with MA, does not improve weight or appetite better than MA alone.
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6.
Effects of megestrol acetate on circulating interleukin-15 and interleukin-18 concentrations in healthy elderly men.
Lambert, CP, Flynn, MG, Sullivan, DH, Evans, WJ
The journals of gerontology. Series A, Biological sciences and medical sciences. 2004;(8):855-8
Abstract
BACKGROUND Interleukin-15 (IL-15) and interleukin-18 (IL-18) are potential regulators of body composition in humans. The authors previously reported that megestrol acetate ingestion causes a large accumulation of adipose tissue and reduces muscle mass. Therefore, the purpose of this investigation was to evaluate the effects of megestrol acetate ingestion on circulating IL-15 and IL-18 concentrations in healthy elderly men. METHODS All participants received 800 mg of megestrol acetate per day during this 12-week study. Megestrol acetate was combined with testosterone injections (100 mg/week), placebo injections, resistance training, or resistance training and testosterone. Resting IL-15 and IL-18 concentrations were measured by enzyme-linked immunosorbent assay at week 0 (pre), week 6 (mid), and week 12 (post). RESULTS The time effect for IL-15 was significant (p = .0008), with the mid and post values being significantly greater than the pre value. The change in IL-15 concentration was not significantly related to the change in muscle mass (r = -.31; p > .05), nor was it related to the change in fat mass (r =.17; p > .05). Differences among groups or over time were not significant for IL-18, nor were correlations between pre body weight and pre IL-18 (r = -.03), pre fat mass and pre IL-18 (r = .14), or the change in fat mass and the change in IL-18 (r = -.07). CONCLUSIONS IL-15 was increased as a result of megestrol acetate ingestion; however, megestrol acetate did not affect circulating IL-18 concentrations, and the change in IL-18 did not correlate with any body composition variables.
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7.
Megestrol acetate-induced weight gain does not negatively affect blood lipids in elderly men: effects of resistance training and testosterone replacement.
Lambert, CP, Sullivan, DH, Evans, WJ
The journals of gerontology. Series A, Biological sciences and medical sciences. 2003;(7):644-7
Abstract
BACKGROUND Megestrol acetate (MA) has been used to stimulate weight gain in elderly populations, with the majority of the weight gain being adipose tissue. Because of the increased energy intake and adipose tissue accrual with MA, it may have a negative effect on circulating lipids. Thus, in this study we examined the effects of MA--alone and in combination with resistance training and/or testosterone replacement--on blood lipids. METHODS All subjects (n = 28) received MA and were randomly assigned to one of four groups: 1) placebo (P) injections, 2) resistance training and P (RT+P), 3) weekly injections of testosterone (T; 100 mg/week), or 4) RT and T (RT+T). RESULTS A significant time effect was observed for total cholesterol (p = 0.0006) and high density lipoprotein (HDL) cholesterol (p = .0003) with the mid and post time points being significantly lower than the pre time points for both variables. For the total cholesterol to HDL ratio, no significant differences between groups or over time (time effect: ) were observed. For triglycerides, there tended to be a time effect (p = .061), with the mid and post time points being lower than the pre time point; however, this effect was not statistically significant. CONCLUSIONS Because it appears from our data that MA does not cause adverse blood lipid changes, the decision to use it should be based on other factors.
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8.
Palliative treatment of cancer anorexia with oral suspension of megestrol acetate.
Tomíska, M, Tomisková, M, Salajka, F, Adam, Z, Vorlícek, J
Neoplasma. 2003;(3):227-33
Abstract
Megestrol acetate (MA) is a progestational agent, currently known as one of the most effective appetite stimulants in patients suffering from cancer anorexia/cachexia syndrome. Oral suspension of this drug may be particularly useful in patients with far advanced disease, where taking larger amount of pills may lead to the decrease of patient compliance. The influence of oral MA suspension on quality of life and nutritional status was evaluated in 22 patients with far advanced cancer suffering from anorexia and more than 5 per cent weight loss, all beyond the scope of anticancer treatment. Most patients had lung or gastrointestinal cancer. QLQ-C30 questionnaire, visual analogue scale (VAS) for appetite, anthropometry, maximal handgrip strength and laboratory data were obtained before treatment and then after 2, 4, and 8 weeks of therapy. Despite of a known high mortality in this prognostically unfavorable group of patients (36% within two months in this study), overall quality of life after the daily dose of 480-840 mg of MA was improved in 63, 56, and 55% of patients remaining on therapy after 2, 4, and 8 weeks, respectively. Appetite was the most successfully influenced parameter with an improvement in VAS in 95% of cases after 2 weeks of therapy (p=0.0001). The drug was well tolerated by the great majority of patients. Oral suspension of megestrol acetate maybean effective palliative treatment for many patients with far advanced cancer suffering from anorexia/cachexia syndrome.
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9.
Effects of testosterone replacement and/or resistance training on interleukin-6, tumor necrosis factor alpha, and leptin in elderly men ingesting megestrol acetate: a randomized controlled trial.
Lambert, CP, Sullivan, DH, Evans, WJ
The journals of gerontology. Series A, Biological sciences and medical sciences. 2003;(2):165-70
Abstract
BACKGROUND Megestrol acetate (MA) has been used to stimulate weight gain in elderly populations with the majority of the gain being adipose tissue. Significant inverse correlations have been reported between weight gain with MA and reductions in circulating the tumor necrosis factor (TNF) alpha receptors. In addition, MA has been shown to reduce circulating interleukin 6 (IL-6) concentrations. We attempted to increase gains in fat-free mass with MA using resistance training and/or testosterone replacement and examined the effects on circulating IL-6, TNF alpha, and leptin in elderly men. METHODS All subjects received MA and were randomly assigned to one of these four groups: placebo (P) injections; resistance training and P (RT+P); weekly injections of testosterone (T; 100 mg/wk); or RT and T (RT+T). Cytokines were measured by enzyme-linked immunosorbent assay Preinterventions, Midinterventions, and after 12 weeks of the interventions (Post). RESULTS IL-6 decreased ( p =.03) over time for the T and P groups when compared to the RT+T and RT+P groups. A time effect ( p =.013) was observed for TNF alpha with Mid and Post both being lower than Pre. A hormone by time interaction ( p =.03) was observed for plasma leptin with individuals not on T exhibiting higher concentrations Post than those individuals on T. A positive correlation was observed (r =.60; p <.05) between changes in fat mass and the change in leptin. CONCLUSION IL-6 was reduced by MA except when RT was undertaken; TNF alpha was reduced over time regardless of group; leptin was higher in individuals not on T than those on T; and the change in plasma leptin was correlated with the change in fat mass.
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10.
Effects of testosterone replacement and/or resistance exercise on the composition of megestrol acetate stimulated weight gain in elderly men: a randomized controlled trial.
Lambert, CP, Sullivan, DH, Freeling, SA, Lindquist, DM, Evans, WJ
The Journal of clinical endocrinology and metabolism. 2002;(5):2100-6
Abstract
Megestrol acetate (MA) (Bristol-Myers Squibb Co., Princeton, NJ) increases weight gain in AIDS and cancer patients and in age-related cachexia; however, the weight gain is predominately fat. We determined if adding resistance exercise and/or testosterone (T) replacement to MA administration would result in a more favorable body composition change than MA alone. Thirty older men (aged 67.0 +/- 5.8) completed this 12-wk study. All subjects received MA and were randomly assigned to one of the following groups: placebo (P) injections, resistance training (RT) and P (RT + P), weekly injections of T (100 mg/wk) or, RT and T (RT + T). The mean increase in body weight for all groups combined was 3.8 kg (P < 0.0001), but this increase was not different between groups. There was a significant interaction for the change in thigh muscle cross-sectional area (P = 0.0006). Thigh muscle cross-sectional area was significantly reduced from baseline by 5.20 [1.62] cm(2) (P = 0.05) in P which was not prevented in T [-4.44 (1.66) cm(2) from baseline; P = 0.04]. RT prevented this decline [+0.61 (1.41) cm(2) from baseline]. Muscle cross-sectional area increased 4.51 (1.69) cm(2) from baseline in RT + T (P = 0.002 vs. P and P = 0.002 vs. T). Despite significant weight gain, MA appears to have an antianabolic effect on muscle size even when combined with T replacement. Resistance exercise attenuated this reduction in muscle mass and when combined with T had an anabolic effect on muscle mass.