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There is inconsistent evidence relating to the effects of megestrol acetate (MA) supplementation on cancer patients suffering from anorexia-cachexia syndrome. This review aimed to examine the dose-response effect of MA supplementation in patients with cancer-associated anorexia/cachexia. Relevant keywords were searched in PubMed, Scopus and ISI Web of Science from inception to June 2023 for randomized controlled trials (RCTs) examining the effect of MA on pathologies in patients with cancer-associated cachexia. Our primary outcomes were changes in body weight and appetite. However, fatigue and quality of life were secondary outcomes. The mean difference (MD) and 95% confidence interval (95% CI) were estimated using the random-effects method. Thirteen trials comprising 1229 participants (mean age 60 years) were identified. The results of our highest versus lowest analysis revealed that MA supplementation was not associated with any increase in body weight (MD: 0.64 kg, 95% CI [-0.11, 1.38], P = 0.093, I 2  = 69.1%; GRADE = very low certainty). Twelve trials, including 14 effect sizes derived from 1369 patients (intervention = 689, control = 680), provided data on the effect of MA on body weight. Subgroup analyses showed a significant increase in body weight following short-term intervention (≤8 weeks) and a combination of radiation/chemotherapy as concurrent treatment. A linear dose-response meta-analysis indicated that each 200 mg/day increment in MA consumption had a significant increase in weight gain (MD: 0.44; 95% CI [0.13, 0.74], P = 0.005; I 2  = 97.1%); however, the magnitude of the effect was small. MA administration significantly affected the quality of life based on pooled effect sizes (MD: 1.15, 95% CI [0.76, 1.54], P < 0.001, I 2  = 0%; n = 2 RCTs including 176 patients; GRADE = very low certainty). However, no significant effect of MA supplementation was observed on appetite (MD: 0.29, 95% CI [-0.05, 0.64], P = 0.096, I 2  = 18.3%; n = 3 RCTs including 163 patients; GRADE = very low certainty) and fatigue (MD: 0.14, 95% CI [-0.09, 0.36], P = 0.236, I 2  = 0%; n = 2 RCTs including 300 patients; GRADE = very low certainty). With very low certainty of the evidence, MA supplementation may not lead to a significantly increased weight gain and other outcomes., (© 2024 The Author(s). Journal of Cachexia, Sarcopenia and Muscle published by Wiley Periodicals LLC.)

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.

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., (© 2018 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of the Society on Sarcopenia, Cachexia and Wasting Disorders.)

Purpose: To determine whether dronabinol administered alone or with megestrol acetate was more, less, or equal in efficacy to single-agent megestrol acetate for palliating cancer-associated anorexia., Patients and Methods: Four hundred sixty-nine assessable advanced cancer patients were randomized to (1) oral megestrol acetate 800 mg/d liquid suspension plus placebo, (2) oral dronabinol 2.5 mg twice a day plus placebo, or (3) both agents. Eligible patients acknowledged that loss of appetite or weight was a problem and reported the loss of 5 pounds or more during 2 months and/or a daily intake of less than 20 calories/kg of body weight., Results: Groups were comparable at baseline in age, sex, tumor type, weight loss, and performance status. A greater percentage of megestrol acetate-treated patients reported appetite improvement and weight gain compared with dronabinol-treated patients: 75% versus 49% (P =.0001) for appetite and 11% versus 3% (P =.02) for > or = 10% baseline weight gain. Combination treatment resulted in no significant differences in appetite or weight compared with megestrol acetate alone. The Functional Assessment of Anorexia/Cachexia Therapy questionnaire, which emphasizes anorexia-related questions, demonstrated an improvement in quality of life (QOL) among megestrol acetate-treated and combination-treated patients. The single-item Uniscale, a global QOL instrument, found comparable scores. Toxicity was also comparable, with the exception of an increased incidence of impotence among men who received megestrol acetate., Conclusion: In the doses and schedules we studied, megestrol acetate provided superior anorexia palliation among advanced cancer patients compared with dronabinol alone. Combination therapy did not appear to confer additional benefit.

The characteristic clinical picture of anorexia, tissue wasting, loss of body weight accompanied by a decrease in muscle mass and adipose tissue, and poor performance status that often precedes death has been named the cancer-related anorexia/cachexia syndrome (CACS). Chronic administration of pro-inflammatory cytokines, including interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor (TNF) either alone or in combination, is capable of reproducing the different features of CACS. High serum levels of these cytokines have been found in cancer patients, which seem to correlate with progression of the tumor. This paper describes a series of experimental and clinical studies demonstrating that: (1) high serum levels of some cytokines, including IL-1, IL-6, and TNF, are present in advanced-stage cancer patients, particularly those with CACS; (2) megestrol acetate (MA) has a beneficial therapeutic effect on CACS symptoms, such as appetite, body weight, and quality-of-life; (3) MA downregulates the synthesis and release of cytokines and relieves the symptoms of CACS; (4) cytokines play a key role in the onset of CACS; (5) medroxyprogesterone acetate (MPA) reduces the in vitro production of cytokines and serotonin (5-hydroxytryptamine, 5-HT) by peripheral blood mononuclear cells (PBMC) of cancer patients; and (6) MA and MPA reduce the cisplatin-induced 5-HT release in vitro from PBMC of cancer patients. Based on these results, a clinical study incorporating MA/MPA in combination with chemotherapy or chemoimmunotherapy may be warranted.