Megestrol Acetate for Appetite Loss and Weight Gain
Megestrol acetate (Megace) at a dose of 160-480 mg/day is recommended for patients with cancer-related appetite loss and weight gain, with one in four patients experiencing appetite improvement and one in twelve experiencing weight gain, though clinicians must be aware of associated risks including thromboembolic events and increased mortality. 1
Dosing and Indications
- For cancer-related anorexia/cachexia: 160-480 mg/day 1
- FDA-approved dosing for cancer treatment: 160 mg/day (40 mg four times daily) for breast cancer; 40-320 mg/day in divided doses for endometrial carcinoma 2
- At least 2 months of continuous treatment is considered adequate to determine efficacy 2
- Higher doses are associated with greater weight improvement than lower doses 3
Efficacy
Megestrol acetate has demonstrated effectiveness for appetite stimulation and weight gain:
- Meta-analyses show that patients treated with megestrol acetate are more likely than those receiving placebo to experience:
- One study found that 16% of patients on megestrol acetate gained ≥15 pounds compared to only 2% on placebo 5
Risk-Benefit Assessment
Benefits
- Appetite improvement in 1 of 4 patients 4
- Weight gain in 1 of 12 patients 4
- Reduced nausea and vomiting in some patients 5
- Improved quality of life measures 4
Risks
- Thromboembolic events in 1 of 6 patients (RR 1.84) 4, 1
- Mortality risk in 1 of 23 patients (RR 1.42) 4, 1
- Edema (RR 1.36) 1
Contraindications and Precautions
Absolute contraindications:
- Hypersensitivity to megestrol acetate
- Concurrent use of dofetilide (significant drug interaction) 1
Use with caution in patients with:
- History of deep vein thrombosis or pulmonary embolism
- Known thrombophilia
- Active malignancy 1
Patient Monitoring
- Regular assessment for thromboembolic events
- Weight and edema assessment
- Blood glucose monitoring
- Cardiovascular assessment 1
Alternative Options
If megestrol acetate is contraindicated or poorly tolerated, consider:
- Corticosteroids (e.g., dexamethasone): Similar appetite improvement to megestrol acetate but with different toxicity profile 4
- Olanzapine: May provide appetite stimulation and additional nausea control 1
- Mirtazapine: Particularly beneficial for patients with concurrent depression 1
Combination Approaches
- A combination regimen including megestrol acetate, medroxyprogesterone, eicosapentaenoic acid, L-carnitine supplementation, and thalidomide has shown superior outcomes compared to single agents 4
- Another study found improved lean body mass, appetite, and quality of life with megestrol acetate plus L-carnitine, celecoxib, and antioxidants compared to megestrol acetate alone 4
Common Pitfalls
- Failing to screen for thromboembolic risk factors before initiating therapy
- Not monitoring for adverse effects, particularly thromboembolic events
- Continuing ineffective treatment beyond 4 weeks without reassessment 1
- Overlooking potential drug interactions 1
Megestrol acetate remains one of the most extensively studied appetite stimulants with the strongest evidence for cancer patients, though clinicians must carefully weigh benefits against risks, particularly the increased risk of thromboembolic events and mortality.