Lesniak, W., Bala, M., Jaeschke, R., & Krzakowski, M. (2008). Effects of megestrol acetate in patients with cancer anorexia-cachexia syndrome—A systematic review and meta-analysis. Polskie Archiwum Medycyny Wewnetrznej, 118, 636–644.

To assess the clinical effects of megestrol acetate (MA) on anorexia-cachexia syndrome (ACS) via systematic review and meta-analysis

The MEDLINE, Embase, and Central databases were used to find research from 2002–2007. The previous systematic review by Lopez et al. (2004) was used to identify additional references. Reference lists of the studies included were also reviewed.

The search keywords used were neoplasm, cancer, cachexia, anorexia, and megestrol acetate.

Inclusion criteria were:

• Randomization
• Studies of advanced-stage cancer (other than hormone-dependent cancer and ACS)
• An MA intervention compared to a placebo or other drugs
• Clinical studies of ACS or MA
• Study of outcomes such as survival, weight change, and performance status
• Study of quality-of-life parameters such as appetite, nausea, pain, fatigue, depression, well-being, or mood.

There were no language restrictions for the studies included. The review also included conference abstracts. No flowchart or additional description of initial study volume or eliminations was provided. The validity of eligible studies was assessed to ensure intent-to-treat analysis and completeness of follow-up.

Findings were presented for studies in 21 different categories. These categories were defined according to MA dose; outcomes evaluated; and whether MA was dispensed in varying doses, compared to a placebo, or compared to other drugs, with relative risk findings for effect size.

• The final number of included studies was 30. Five of these were abstracts.
• All studies included patients with advanced-stage cancer.
• In most studies, participants had a variety of cancers. In several studies, lung cancer was a criterion for inclusion; several more studies involved head and neck cancer.

Pooled analysis was completed and statistical significance of overall effects was calculated via the Z-test. Homogeneity of results between studies was analyzed with the chi-square test. Results were summarized by GRADE group categorization.

MA administration is associated with appetite improvement, increased probability of weight gain, and a higher probability of delay in deterioration of performance status. The conclusions regarding MA's influence on other symptoms, quality-of-life indices, and performance status were not clear.

There appears to be a dose-response relationship for achievement of weight gain. To obtain improved appetite, it appears that a low dose of MA (160 mg) is as effective as higher doses. At this low dose, there was a beneficial trend compared to the placebo, and a significant effect of a dose increase has not been demonstrated.

The effects of MA are not significantly different than those of glucocorticosteroids. In a previous review, lower-extremity edema in short-term follow-up and potential increased risk of embolic complications in long-term follow-up were identified as adverse effects of MA

Results suggest that MA has a beneficial effect on appetite.
 

• This review included only advanced cancer cases. The role of MA earlier in the course of disease was not addressed here.
• Studies reviewed were found to be of low quality. Due to this, additional randomized controlled trials with MA are suggested.
• It is suggested that further study of MA's role in ACS include determination of the relative value attributed by patients to individual symptoms affected by MA's use.