Primary Indication for Megestrol Acetate (Megace)
The primary FDA-approved indication for megestrol acetate is the palliative treatment of advanced carcinoma of the breast or endometrium (i.e., recurrent, inoperable, or metastatic disease). 1
FDA-Approved Indication
- Megestrol acetate is officially indicated for the palliative treatment of advanced breast or endometrial carcinoma 1
- It should not be used in place of currently accepted procedures such as surgery, radiation, or chemotherapy 1
Common Off-Label Use in Cancer-Related Anorexia/Cachexia
- Despite not being FDA-approved for this indication, megestrol acetate is widely used as an appetite stimulant in cancer-related anorexia and cachexia 2, 3
- The American Society of Clinical Oncology (ASCO) guidelines recognize megestrol acetate as a treatment option for cancer cachexia, though they note there are currently no FDA-approved medications specifically for cancer cachexia 2
- Patients receiving megestrol acetate are 2.57 times more likely to experience appetite improvement and 1.55 times more likely to gain weight compared to those receiving placebo 2, 4
Mechanism of Action for Appetite Stimulation
- Megestrol acetate stimulates appetite through multiple mechanisms, including:
- Downregulation of proinflammatory cytokines that contribute to cachexia
- Influence on the hypothalamic appetite regulation center
- Potential glucocorticoid-like effects at higher doses 5
Dosing for Appetite Stimulation
- The optimal dosing for appetite stimulation appears to be between 480-800 mg per day 3
- Higher doses are associated with greater weight improvement, though they may also increase the risk of adverse effects 2, 6
Important Risks and Precautions
- Thromboembolic phenomena (including thrombophlebitis and pulmonary embolism) occur at 1.84 times the rate of placebo 2, 3
- Increased mortality risk has been documented, with a relative risk of 1.42 compared to placebo 3
- Weight gain from megestrol acetate is primarily adipose tissue rather than skeletal muscle, potentially limiting its clinical benefit 3, 5
- Regular monitoring for thromboembolic events and adrenal function is recommended, especially with long-term therapy 3
Alternative Options for Appetite Stimulation
- Corticosteroids (e.g., dexamethasone) may be considered as an alternative to megestrol acetate, with similar appetite-stimulating effects but different toxicity profiles 2, 4
- The choice between megestrol acetate and corticosteroids should consider expected survival and comorbidities 3
While megestrol acetate is commonly used for cancer-related anorexia and cachexia, clinicians should be aware that this represents an off-label use, as the only FDA-approved indication is for palliative treatment of advanced breast or endometrial carcinoma.