Lopez, A.P., i Figuls, M.R., Cuchi, G.U., Berenstein, E.G., Pasies, B.A., Alegre, M.B., & Herdman, M. (2004). Systematic review of megestrol acetate in the treatment of anorexia-cachexia syndrome. Journal of Pain and Symptom Management, 27, 360–369.

To assess the efficacy and safety of megestrol acetate in improving appetite, weight gain, and health-related quality of life in patients with anorexia-cachexia syndrome who had advanced cancer, AIDS, or other underlying pathologies. Other aims were to evaluate the efficacy of different doses and the safety of megestrol acetate.

The following databases were searched: Cochrane Collaboration, Cochrane Controlled Trials Register, MEDLINE, and Embase. A hand search of reference lists was completed. The keywords used were randomized controlled clinical trial, double-blind, single-blind, megestrol acetate, terminally ill, terminal care, and wasting syndrome. Variants of megestrol acetate were also keywords. There was no language restriction. Data were extracted by two reviewers who used the Jadad scale to assess quality. A third reviewer participated if needed.

Of the 296 studies identified, 26 published between 1980 and 2002 met the inclusion criteria. Of these, 19 compared megestrol acetate to a placebo, 6 compared megestrol acetate to other drugs, and 6 studied the effectiveness of different dose levels. The quality of the studies was rated on the Jadad scale: 10 were high-quality, 7 were medium-quality, and 9 were low-quality.

• A total of 3,887 patients had cancer or AIDS and had a clinical diagnosis of anorexia-cachexia syndrome or indicative symptoms (e.g., loss of appetite, decrease in muscle mass).
• Of these patients, 86% (3,368) had cancer, 11% (427) had AIDS, and 2% (81) had other diagnoses.
• Of the patients with cancer, 40% had lung cancer, 23% had gastrointestinal cancer, 7% had head and neck cancer, 2% had pancreatic cancer, 2% had gynecologic cancer, and 26% had other cancers.
• Mean age in the megestrol acetate group was 57 years. Thirty-one percent were women.
• Mean age in the placebo group was 59 years. Thirty-two percent were women.
• There was no difference in sociodemographic characteristics between the megestrol acetate and placebo groups. 
• Megestrol acetate doses ranged from 160 to 1,600 mg/day. The most frequently used dose was 480 mg/day.
• Ten of the 26 studies administered a dose of 800 mg/day.

A meta-analysis of the studies assessing appetite had homogeneous results, showing statistically significant improvement with megestrol acetate over the placebo (RR = 2.33, 95% CI 1.52–3.59)

For weight gain, results were homogeneous and in favor of megestrol acetate, but not statistically significant (RR = 1.88, 95% CI 1.43–2.47).

For quality of life, there was significant heterogeneity because of the variety of instruments used. When the results using only the Karnofsky Performance Status Scale were analyzed, heterogeneity was not observed, and the results were positive in favor of megestrol acetate (RR = 1.64, 95% CI 1.06–2.55). Subgroup analysis in patients with cancer showed positive results in favor of megestrol acetate over placebo on appetite (RR = 2.33, 95% CI 1.52–3.59), weight gain (RR = 2.16, 95% CI 1.45–3.21), and quality of life (RR = 1.81, 95% CI 1.13–2.89).

In comparing megestrol acetate to other drugs, it showed benefit in terms of weight gain. No difference was noted between megestrol acetate and other drugs in terms of quality of life. For appetite, megestrol acetate was superior to dronabinol, but showed no advantage to other drugs studied.

In comparing the efficacy of different megestrol acetate doses, the only statistically significant result was observed in patients with cancer, for whom higher doses were associated with greater weight gain (RR = 1.65, 95% CI 1.00–2.73). There were no statistically significant differences between treatment and placebo groups in terms of adverse events, excepting edema, which was greater in the megestrol acetate group (RR = 1.67, 95% CI 1.22–2.28).

When compared with a placebo, there were significant improvements in appetite and weight gain in patients with cancer who were treated with megestrol acetate. This meta-analysis confirms the results of earlier systematic reviews that demonstrated megestrol acetate's advantages over placebo in terms of weight gain and improved appetite. This review did not define the optimal dose of megestrol acete.

Given the adverse events profile, megestrol acetate is a safe treatment option.