What is the recommended use and dosage of Megace (megestrol acetate)?

Megestrol Acetate (Megace): Recommended Use and Dosage

Megestrol acetate may be offered as a short-term trial for cancer-related anorexia and cachexia at doses of 400-800 mg/day, with higher doses associated with greater weight improvement, though it carries significant risks including increased mortality and thromboembolic events. 1, 2

Indications and FDA-Approved Uses

• FDA-approved indications include breast cancer (160 mg/day divided as 40 mg four times daily) and endometrial carcinoma (40-320 mg/day in divided doses) 3
• Not FDA-approved specifically for cancer cachexia, though commonly used off-label for this purpose 1
• May be considered for patients experiencing loss of appetite and/or body weight due to cancer 1

Dosing for Appetite Stimulation in Cancer Cachexia

• For cancer-related anorexia/cachexia, dosages typically range from 400-800 mg/day 2, 4
• Higher doses (480-800 mg/day) are associated with greater improvement in appetite and weight 1, 5
• Initial dosing of 160 mg/day may be reasonable in routine clinical practice, with dose escalation if needed 6
• The concentrated suspension formulation (625 mg/5mL) allows for more convenient once-daily dosing of a teaspoon (5mL) compared to larger volumes of standard formulations 7

Efficacy for Appetite Stimulation

• Patients receiving megestrol acetate are 2.57 times more likely to experience appetite improvement compared to placebo 1, 2
• Weight gain occurs in approximately 1 in 12 patients (8%), with significant weight gain (≥15 lbs) reported in up to 16% of patients 2, 8
• Improvements in quality of life measures have been documented (RR 1.91) 1
• Weight gain is primarily adipose tissue rather than skeletal muscle, potentially limiting clinical benefit 1, 9

Risks and Adverse Effects

• Significant increased risk of thromboembolic events (RR 1.84) 1, 9
• Increased mortality risk (RR 1.42) compared to placebo 1, 9
• Other adverse effects include edema (RR 1.36) 1
• Adrenal suppression may occur with prolonged use 9
• Mild edema is the most commonly reported side effect in clinical trials 8

Monitoring Recommendations

• Regular assessment for thromboembolic phenomena is essential 9
• Monitor weight changes to assess response 9
• Assess adrenal function in patients on long-term therapy 9
• Duration of therapy should be limited, with benefits weighed against risks 9

Alternative Options

• Dexamethasone (2-8 mg/day) may be considered as an alternative with faster onset of action, making it suitable for patients with shorter life expectancy 4
• Combination therapy with olanzapine and megestrol acetate has shown promise, with 85% of patients experiencing ≥5% weight gain over 8 weeks compared to 41% with megestrol acetate alone 1, 2
• Mirtazapine (7.5-30 mg at bedtime) can be effective for patients with concurrent depression and appetite loss 4

Clinical Decision Algorithm

1. First-line consideration: For patients with cancer-related anorexia/cachexia with expected survival >2-3 months, start megestrol acetate at 400 mg/day 2, 4
2. Dose adjustment: If insufficient response after 2-4 weeks, consider increasing to 800 mg/day 5
3. Duration assessment: Evaluate response after at least 2 months of continuous treatment 3
4. Alternative for shorter prognosis: For patients with very limited life expectancy (weeks), consider dexamethasone instead due to faster onset of action 4
5. Discontinuation: Stop therapy if no significant benefit occurs or when death appears imminent 1

Important Caveats

• The type of weight gain is primarily adipose tissue, not skeletal muscle, which may limit functional improvement 1, 9
• Regular reassessment is essential to evaluate benefit versus harm 4
• Lower starting doses should be used for elderly patients with close monitoring for side effects 4
• The optimal duration of therapy is not well-established, but benefits should be weighed against risks, particularly for longer-term use 2