What is megestrol acetate used for?

Uses of Megestrol Acetate

Megestrol acetate is primarily used for the palliative treatment of advanced breast or endometrial carcinoma and as an appetite stimulant for cancer-related anorexia and cachexia syndrome. 1, 2

FDA-Approved Indications

• Megestrol acetate is FDA-approved for the palliative treatment of advanced carcinoma of the breast or endometrium (recurrent, inoperable, or metastatic disease) 1
• It is also FDA-approved for the treatment of anorexia, cachexia, or unexplained weight loss in patients with AIDS 3

Off-Label Uses

• Megestrol acetate is widely used as an appetite stimulant in patients with cancer-associated anorexia-cachexia syndrome 2, 4
• It has demonstrated effectiveness in improving appetite and weight gain in cancer patients, with patients 2.57 times more likely to experience appetite improvement compared to placebo 5, 6
• It may be used in children with weight loss due to cancer and/or cancer therapy, though studies are more limited in this population 7

Mechanism of Action

• Megestrol acetate stimulates appetite through multiple mechanisms, including:
  • Downregulation of proinflammatory cytokines that contribute to cachexia 8
  • Influence on the hypothalamic appetite regulation center 8
  • Potential glucocorticoid-like effects at higher doses 8
• For its antineoplastic effects, megestrol acetate works by:
  • Inhibiting pituitary gonadotropin production, resulting in decreased estrogen secretion 1
  • Modifying the action of other steroid hormones 1
  • Exerting direct cytotoxic effects on tumor cells 1

Dosing Considerations

• The optimal dosing for appetite stimulation appears to be between 480-800 mg per day, with higher doses associated with greater weight improvement 4, 9
• For cancer patients, doses typically range from 320-840 mg daily 9
• In clinical trials, weight gain was observed in the majority of patients, with a median time to peak weight of approximately 14 weeks 10

Important Risks and Precautions

• Thromboembolic phenomena, including thrombophlebitis and pulmonary embolism, are significant risks (RR 1.84 compared to placebo) 2, 4
• Increased mortality risk has been documented (RR 1.42 compared to placebo) 4
• Weight gain from megestrol acetate is primarily adipose tissue rather than skeletal muscle, potentially limiting its clinical benefit 4, 8
• Adrenal suppression can occur with long-term therapy 4, 8
• Edema is more common in patients taking megestrol acetate (RR 1.36 compared to placebo) 2

Monitoring Recommendations

• Regular assessment for thromboembolic phenomena is essential due to the significantly increased risk 4, 8
• Weight should be monitored to assess response to therapy 8
• Adrenal function should be monitored in patients on long-term therapy 4, 8

Alternative Options

• Corticosteroids (e.g., dexamethasone) may be considered as an alternative for appetite stimulation in cancer patients, with similar appetite-stimulating effects but different toxicity profiles 2, 4
• Combination therapy approaches, such as megestrol acetate plus olanzapine, have shown improved outcomes in some studies, with patients in the combination arm more likely to experience weight gain of ≥5% (85% vs 41%) 2, 5