Berenstein, E.G., & Ortiz, Z. (2005). Megestrol acetate for the treatment of anorexia-cachexia syndrome. Cochrane Database of Systematic Reviews, 2, CD004310. 

To evaluate the efficacy and safety of megestrol acetate (MA) in palliating anorexia-cachexia syndrome in patients with cancer, AIDS, or other underlying pathologies

Studies that met the following eligibility criteria were reviewed.

• Double-blind, single-blind, or unblended randomized controlled trials (RCTs)
• RCTs that assessed the use of MA compared to a placebo or other drug treatments in patients diagnosed with anorexia-cachexia related to cancer, AIDS, or other underlying pathologies
• Crossover studies that reported the results of the first phase of the study

Data extraction was conducted by two independent authors. Methodological quality was assessed using the Oxford scale (Jadad, 1996). Scores for methodological quality were generally high. Studies in which more that 50% of patients were lost to follow-up were excluded from the analysis.

• Thirty trials, which included a total of 4,123 participants, met the eligibility criteria.
• Mean participant age was 58 years in the treatment groups and 57 years in the control groups.
• The proportion of males to females in the treatment groups was 1,140/502 and 1,733/731 in the control groups. 
• The doses of MA administered ranged from 100 mg to 1,600 mg per day.
• Twenty-one trials compared different doses of MA with a placebo; four compared different doses of MA with other drugs; three compared different doses of MA; and two compared MA with other drugs and a placebo.

Results for MA versus placebo: In patients with cancer, a statistically significant improvement in appetite was observed in the patients treated with MA. Weight gain also was observed in this group.

Results for MA versus other drugs: MA did not show benefits in terms of appetite improvement in comparison to other drugs. Significant differences in quality of life were not reported.

Results for different dose levels of MA: Using 400–800 mg as a cutoff and comparing high to low doses, significant differences in appetite outcomes could not be appreciated.

MA improves appetite and weight gain in patients with cancer. Due to study heterogeneity, no overall conclusion can be drawn about its impact on quality of life; a more systematic approach was suggested for the measurement of quality of life in the trials. The clinical effects of MA do not appear to be dose-related, and the mechanism by which MA increases weight gain is unknown. 

MA cannot be recommended for use in patients with AIDS or anorexia-cachexia related to other pathologies. Edema, included in the adverse event profile of MA, is the only significant difference between the treatment and a placebo.