Prospective randomised trial of two dose levels of megestrol acetate in the management of anorexia-cachexia syndrome in patients with metastatic cancer. Megestrol acetate stimulates weight gain and ventilation in underweight COPD patients. 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. Usage of megestrol acetate in the treatment of anorexia-cachexia syndrome in the elderly. Usefulness of megestrol acetate in cancer cachexia and anorexia. A placebo-controlled study. Megestrol acetate for anorexia in patients with far-advanced cancer: a double-blind controlled clinical trial. Megestrol acetate in advanced, progressive, hormone-insensitive cancer. Effects on the quality of life: a placebo-controlled, randomised, multicentre trial. Controlled trial of megestrol acetate for the treatment of cancer anorexia and cachexia. Megestrol acetate in patients with AIDS-related cachexia.
Two doses of megestrol acetate (MA) have been prospectively compared in a random fashion as treatment for cancer-related anorexia-cachexia syndrome (ACS) in 122 patients with progressive soft tissue sarcoma, colorectal, lung, head and neck and renal cancer resistant to systemic chemotherapy. After 30 days of MA, 55% of patients receiving MA at 160 mg day-1 reported an increase in appetite, 27% of patients no variation and 18% complained of a decrease in appetite. Patients treated with MA at 320 mg day-1 reported an increase in appetite in 68% of cases, a stabilisation in 20% of cases and a decrease in 12%. Although an increase in appetite was more frequently observed in patients receiving MA at 320 mg day-1, however this difference was not statistically significant (P = 0.305). After 30 days of MA, 31% of patients treated with MA at 160 mg day-1 showed an increase in body weight, 25% a stabilisation and 44% a decrease. In the group of patients treated with MA at 320 mg day-1, 45% reported an increase in body weight, 16% no change and 23% weight loss. Although there was a trend favouring the higher dose of MA, overall analysis however failed to detect any statistically significant difference between the two treatment arms (P = 0.242). Twenty-seven patients pretreated with 160 mg day-1 and 23 patients treated with 320 mg day-1 received further therapy with MA at the dose of 320 and 480 mg day-1 respectively. In the group of 22 patients treated with 320 mg day-1 four (18%) reported an increase in body weight, eight (36%) an improvement in appetite, but none had an increase in performance status. Among the 20 evaluable patients treated with 480 mg day-1, two (10%) had an increase in body weight, four (20%) an improvement in appetite, but none reported an increase in performance status. No difference in median survival was detected between the two arms. Toxicity was mild and predictable. In conclusion, the data achieved in the present study confirm the clinical safety and effectiveness of oral MA in the management of ACS in patients with advanced cancer resistant to systemic chemotherapy. Moreover, data concerning the dose escalation of MA dosage in unresponsive patients suggest that a step by step increase in MA dosage could be the best way of administering MA for the management of ACS and that the increase of MA dosage over 480 mg day-1 will probably be useless in the vast majority of cases. Data on body weight suggest that after 2 weeks' therapy MA could be stopped or its dosage tailored to patients' needs since the majority of patients respond after only 15 days of MA. To assess the effect of megestrol acetate (MA), a progestational appetite stimulant commonly used in patients with AIDS and cancer, on body weight and composition, respiratory muscle strength, arterial blood gas levels, and subjective perceptions in COPD patients.
                Prospective, double-blind, randomized, placebo-controlled trial conducted on an outpatient basis at 18 sites.
                Underweight (< 95% ideal body weight) COPD patients > or = 40 years old.
                Either MA, 800 mg/d oral suspension, or placebo at a 1:1 ratio for 8 weeks.
                Of 145 randomized patients (63% men), 128 patients completed the trial. Body weight increased by 3.2 kg in the MA group and 0.7 kg in the placebo group (p < 0.001). Anthropometric and dual-energy radiograph absorptiometry assessments confirmed that weight gain was mainly fat. Spirometry and maximal voluntary ventilation showed no significant changes from baseline in either group, and the difference in the change in maximum inspiratory pressure between groups was not significant. The 6-min walk distances did not differ statistically between groups at week 2 and week 4, but were greater in the placebo group at week 8 (p = 0.012). Consistent with the known ability of MA to stimulate ventilation, PaCO(2) decreased (4.6 mm Hg, p < 0.001) and PaO(2) increased (2.8 mm Hg, p < 0.04) in the MA group. Questionnaires revealed that body image and appetite improved in the MA group but not the placebo group. Adverse event frequency and type were similar in both groups, but cortisol and testosterone (in men) levels decreased substantially in the MA group.
                We conclude that MA safely increased appetite and body weight, stimulated ventilation, and improved body image in underweight COPD patients, but did not improve respiratory muscle function or exercise tolerance. 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.
                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.
                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.
                This EPA supplement, either alone or in combination with MA, does not improve weight or appetite better than MA alone. The aim of this review is to assess the efficacy and safety of megestrol acetate (MA) in geriatric cachexia. The paper presented here reviews a previously published study of MA use in 69 patients in a randomized double blind placebo-controlled trial. This paper will also address the underlying pathogenesis of cachexia (specifically, the role of cytokines) along with the use of MA, its mechanism of action and its side effects.
                To compare the effects of MA oral suspension (O.S.), 800 mg/day, versus placebo on weight in geriatric nursing home patients with weight loss or low body weight.
                Twelve weeks, randomized, double-blind, placebo-controlled trial with a 13-week follow-up period.
                Northport VAMC Nursing home patients with weight loss of * 5% of usual body weight over the past 3 months, or body weight 20% below their ideal body weight.
                Patients were randomly assigned to receive placebo or MA 800 mg/d for 12 weeks and were then followed for 13 weeks off treatment and mortality 4 years post treatment.
                Primary outcome- weight and appetite change. Secondary outcome-sense of well being, enjoyment of life, change in depression scale, laboratory nutrition parameters, energy intake counts, body composition, and adverse events.
                At 12 weeks there were no significant differences in weight gain between treatment groups, while MA-treated patients reported significantly greater improvement in appetite, enjoyment of life, and well being. At week 25 (3 months after treatment), 61.9% of MA-treated patients had gained * 1.82 kg (4 lbs) compared to 21.7% of placebo patients. There was no difference in survival between MA and placebo groups. Considering possible confounders, higher initial IL-6, initial TNFR-p75 levels, and final neutrophil percentage were associated with elevated mortality, whereas higher initial pre-albumin, initial albumin, final pre-albumin, final albumin and final weight gain were associated with decreased death. To assess the effect of megestrol acetate (MA) on the appetite and weight of cancer patients with nonhormone-dependent tumors, a double-blind, placebo-controlled trial was designed. One hundred fifty patients were included: 76 were given MA (240 mg/day orally) for at least 2 months, and 74 were given placebo (P). Body weight, subjective sense of appetite (SSA) evaluated by an analogic linear visual scale scored from 1 to 10, and performance status (PS) were measured before therapy and monthly thereafter. No differences in body weight before and after treatment could be found in any group. However, 32% of the patients in the MA group (95% confidence interval: 20.1-44.6%) gained 2 or more kilograms (P less than 0.001). This group also showed an improvement in SSA (P less than 0.01): an increase greater than or equal to 2 points appeared in 57.5% of patients (95% confidence interval 44.6-69.4%). There was no significant difference in PS for the treatment groups before or after therapy. The percentage of reported adverse events did not differ significantly from one treatment group to the next. We conclude that therapy with MA at a dose of 240 mg/day improved SSA and was associated with moderate weight gain in patients with hormone-insensitive malignancies. The aim of this study was to evaluate a low-dose regimen of megestrol acetate (MA; 320 mg/day) on appetite in advanced cancer patients. Out-patients with far-advanced non-hormone responsive tumours and loss of appetite were randomised in a phase III trial, with two consecutive phases: a 14-day double-blind placebo controlled phase (phase A) and a 76-day open phase (phase B). During phase A, patients were treated with MA, two 160 mg tablets/day, or placebo. In phase B, the MA dose was titrated to clinical response in both groups. Appetite, food intake, body weight, performance status, mood and quality of life were evaluated with standardised measures; patients' global judgement about treatment efficacy was also requested. Of 42 patients entering the study, 33 (17 MA and 16 placebo) were evaluable for efficacy. The appetite score improved significantly with MA after 7 days (P = 0.0023), and this effect was still significant at 14 days (P = 0.0064). Patients judged the treatment with MA effective in 88.2% of cases (14th day), whilst placebo was considered effective by 25% (P = 0.0003). None of the other measures showed significant changes during treatment. The remarkable effect on appetite evident after 7 days, without serious side-effects, shows that MA can produce significant subjective effects at a low-dose even in patients with far-advanced disease. A randomised double-blind placebo-controlled multicentre trial was performed to investigate the effects of megestrol acetate (MA) on the quality of life (QoL), appetite, weight and survival of patients with advanced, incurable, hormone-insensitive cancer. QoL was assessed at the start of treatment and at 4, 8 and 12 weeks, using the EORTC-QLQ-C30 instrument. 255 patients were randomised to 320 mg of MA daily or placebo for 12 weeks. 244 patients were assessable at baseline, 190 at 4 weeks (placebo 94; MA 96), 150 at 8 weeks (placebo 69; MA 81) and 112 at 12 weeks (placebo 55; MA 57). A beneficial effect of MA on appetite loss was observed at week 4 (P < 0.0001) and possibly at week 8 (P = 0.058). Further weight loss during treatment was significant only in the placebo group. In the first 8 weeks, changes in mean global QoL were small and similar in both groups. By 12 weeks the decrease in mean global QoL was more pronounced in the MA group (P = 0.028), which was related to a deterioration in physical function, while psychosocial function was not affected. Survival was not affected by MA, and side-effects were mild. The results show that MA has a beneficial effect on appetite and that it may retard weight loss with no adverse impact on survival and with mild toxicity. However, MA does not appear to improve global QoL as measured by the EORTC QLQ-C30. Preliminary information has suggested that megestrol acetate leads to appetite stimulation and nonfluid weight gain in patients with breast cancer, other cancers, and AIDS. Pursuant to this, we developed a randomized, double-blind, placebo-controlled trial of megestrol acetate in patients with cancer-associated anorexia and cachexia. We randomly assigned 133 eligible patients to receive 800 mg of megestrol acetate per day or a placebo. Patients assigned to megestrol acetate more frequently reported improved appetite (P = .003) and food intake (P = .009) when compared with patients receiving the placebo. A weight gain of 15 lb or more over baseline was seen in 11 of 67 (16%) patients receiving megestrol acetate compared with one of 66 (2%) given the placebo (P = .003). Patients receiving megestrol acetate reported significantly less nausea (13% vs. 38%; P = .001) and emesis (8% vs. 25%, P = .009). No clinically or statistically significant toxic reactions were ascribed to megestrol acetate, with the exception of mild edema. This study convincingly demonstrated that megestrol acetate can stimulate appetite and food intake in patients with anorexia and cachexia associated with cancer, leading to significant weight gain in a proportion of such patients. To compare the effects of oral suspensions of megestrol acetate, 800 mg/d, and placebo on body weight in patients with acquired immunodeficiency syndrome (AIDS)-related weight loss.
                Randomized, double-blind, placebo-controlled trial.
                Outpatient community and university patient care setting.
                Consecutive patients with AIDS who had substantial weight loss and anorexia were enrolled. Of 271 patients, 270 and 195 were evaluable for safety and efficacy, respectively.
                Patients were randomly assigned to receive placebo or megestrol acetate (100 mg, 400 mg, or 800 mg) daily for 12 weeks.
                The primary efficacy criterion was weight gain. Patients were evaluated at 4-week intervals for changes in weight and body composition, caloric intake, sense of well-being, toxic effects, and appetite.
                For evaluable patients receiving 800 mg of megestrol acetate per day, 64.2% gained 2.27 kg (5 pounds) or more compared with 21.4% of patients receiving placebo (P < 0.001). An intent-to-treat analysis showed significant differences (P = 0.002) between those receiving placebo and those receiving 800 mg of megestrol acetate for the number of patients who gained 2.27 kg (5 pounds) or more (8 of 32 [25%] compared with 38 of 61 [62.3%], respectively). Compared with patients receiving placebo at the time of maximum weight change, evaluable patients receiving megestrol acetate, 800 mg/d, reported improvement in overall well-being and had an increase in mean weight gain (-0.725 compared with 3.54 kg [-1.6 compared with +7.8 pounds]; P < 0.001), lean body mass (-0.772 compared with +1.14 kg [-1.7 compared with +2.5 pounds]; P < 0.001), appetite grade (P < 0.001), and caloric intake (-107 compared with +645.6 calories/d; P = 0.001).
                In patients with AIDS-related weight loss, megestrol acetate can stimulate appetite, food intake, and statistically significant weight gain that is associated with a patient-reported improvement in an overall sense of well-being.
This review shows that MA improves appetite and is associated with slight weight gain in cancer, AIDS and in patients with other underlying pathology. Despite the fact that these patients are receiving palliative care they should be informed of the risks involved in taking MA.