What is the role of Megace (megestrol acetate) as an appetite stimulant for weight gain?

Megestrol Acetate as an Appetite Stimulant for Weight Gain

Megestrol acetate is effective for appetite stimulation and weight gain in patients with cancer-related anorexia/cachexia, but carries significant risks including thromboembolic events (1 in 6 patients) and increased mortality (1 in 23 patients). 1, 2

Efficacy and Indications

• FDA-approved for treatment of anorexia, cachexia, or unexplained significant weight loss in patients with AIDS 3
• Commonly used off-label for cancer-related anorexia/cachexia 1, 2
• Effectiveness:
  • 1 in 4 patients experience increased appetite
  • 1 in 12 patients achieve weight gain 1
  • Weight gain primarily consists of fat mass rather than lean body mass 4

Dosing Recommendations

• Minimum effective dose: 160 mg/day 2, 5
• Optimal dose range: 480-800 mg/day 2
• No evidence that doses above 480 mg/day provide additional efficacy 2
• Dose-response relationship exists for appetite stimulation, but higher doses increase cost and side effects 5

Risk Profile

Megestrol acetate carries significant risks that must be carefully considered:

• Thromboembolic events: 1 in 6 patients (relative risk 1.84) 1, 2
• Mortality risk: 1 in 23 patients will die (relative risk 1.42) 1, 2
• Edema (relative risk 1.36) 2
• No significant improvement in quality of life compared to placebo 6, 7

Comparative Effectiveness

• Superior to dronabinol (cannabis derivatives) for weight gain (75% vs 49% of patients) and appetite improvement (11% vs 3%) in cancer patients 1
• More effective than placebo for weight gain (mean difference 2.25 kg) 6
• Combination therapy approaches may yield better outcomes:
  • Megestrol acetate + L-carnitine + celecoxib + antioxidants improves lean body mass, appetite, and quality of life compared to megestrol acetate alone 1, 2

Clinical Algorithm for Use

1. First, address reversible causes of anorexia (depression, pain, constipation, nausea/vomiting, oral candidiasis) 1, 2
2. Consider megestrol acetate when:
   • Patient has cancer or AIDS-related anorexia/cachexia
   • Life expectancy is months-to-weeks or weeks-to-days
   • Increased appetite is an important aspect of quality of life 1
3. Start at 160 mg/day, can increase to 480 mg/day if needed 2, 5
4. Monitor weekly for:
   • Weight changes
   • Thromboembolic complications
   • Fluid retention 2
5. Discontinue if ineffective after 4 weeks 2

Important Caveats

• Weight gain is primarily fat mass, not lean body mass 4
• Consider combining with exercise program when appropriate to maintain lean body mass 4
• Particularly effective in women with cancer-related cachexia 4
• May be beneficial in pediatric cancer patients with fewer side effects than in adults 8
• Should be used in conjunction with non-pharmacological approaches (small frequent meals, high-calorie foods, pleasant eating environment) 2