# 100 Megestrol Acetate for Cancer Anorexia/Cachexia

FAST FACTS AND CONCEPTS #100

Author(s): Mike Salacz MD

Background
Cachexia occurs in up to 80% of cancer patients. Abnormal weight loss (more than 5-10% of pre-morbid weight) results in significant physical and psychological morbidity and is an independent risk factor for early mortality. Attempts to treat anorexia with enteral (e.g. tube feeding) or parenteral feedings (e.g. total parenteral nutrition – see Fast Fact #190) have demonstrated limited efficacy, at the price of increased morbidity. This Fast Fact discusses megestrol acetate, a synthetic progestin, which has been extensively studied as an appetite stimulant.

Outcome Data
Clinical trials have demonstrated that megestrol is:

  • Equally efficacious to dexamethasone as an appetite stimulant.
  • Superior to dronabinol (see Fast Fact #93) in appetite stimulation and non-fluid weight gain.
  • Effective, when used concurrently with radiation therapy in lung or head and neck cancer to reduce treatment associated weight loss.
  • Associated with fewer side effects than corticosteroids.

However, despite these apparent benefits, available data suggest that weight gain is largely adipose tissue (not lean muscle) and only one study has demonstrated a quality of life benefit. No study has shown a survival advantage. Overall only 20-30% of advanced cancer patients will have a significant response (weight gain > 5%), with a median time to response of 6-8 weeks.

Dosing
The optimal timing to initiate treatment with megestrol (prophylactic or therapeutic) and the optimal duration of therapy are unknown. Megestrol is dosed orally, once daily. There is an increasing dose/response curve from 160 to 800 mg/day; doses above 800mg/day have no additional benefit. Different strategies include beginning at 400mg per day and titrating for effect to 800 mg/day. Alternatively, dosing can begin at 800 mg/day. Generally, megestrol is dosed in the elixir form both for patient convenience and cost (see below). Megestrol is 60-80% excreted in urine; no guidelines are available for dosing in renal impairment.

Costs (AWP = average wholesale price)

  • Tablet: 20 mg (AWP = $69/100 pills); 40 tablets = 800 mg = $27.60/day. 40 mg (AWP = $117/100 pills); 20 tablets = 800 mg = $23.50/day
  • Elixir: 40 mg/ml (AWP = $144/480ml) = 20ml = 800 mg = $6/day

Side Effects
Side effects are mild, but can include thromboembolic events (use with caution in patients with history thromboembolism), adrenal suppression with insufficiency upon abrupt discontinuation, hypertension, hyperglycemia, breakthrough uterine bleeding and skin photosensitivity.

References

  1. Inui A. Cancer anorexia-cachexia syndrome: current issues in research and management. CA Cancer J Clin. 2002; 52:72-91.
  2. Jatoi A. On appetite and its loss. J Clin Oncol. 2003; 21(9, Suppl):S79-S81.
  3. Jatoi A. Dronabinol versus megestrol acetate versus combination therapy for cancer-associated anorexia: a North Central Cancer Treatment Group study. J Clin Oncol, 2002; 20:567-73.
  4. McQuellon RP. Supportive use of megestrol acetate with head/neck and lung cancer patients receiving radiation therapy. Int J Radiat Oncol Biol Phys. 2002; 52:1180-5.
  5. Tisdale MJ. Biology of Cachexia. J Natl Cancer Inst. 1997; 89:1763-73.

Fast Facts and Concepts are edited by Drew A Rosielle MD, Palliative Care Center, Medical College of Wisconsin. For more information write to: drosiell@mcw.edu. More information, as well as the complete set of Fast Facts, are available at EPERC: www.eperc.mcw.edu.

Version History: This Fast Fact was originally edited by David E Weissman MD and published in October 2003. Re-copy-edited in April 2009.

Copyright/Referencing Information: Users are free to download and distribute Fast Facts for educational purposes only. Salacz M. Megestrol Acetate for Cancer Anorexia/Cachexia. Fast Facts and Concepts. October 2003; 100. Available at: http://www.eperc.mcw.edu/fastfact/ff_100.htm.

Disclaimer: Fast Facts and Concepts provide educational information. This information is not medical advice. Health care providers should exercise their own independent clinical judgment. Some Fast Facts cite the use of a product in a dosage, for an indication, or in a manner other than that recommended in the product labeling. Accordingly, the official prescribing information should be consulted before any such product is used.

ACGME Competencies: Medical Knowledge, Patient Care, Practice-Based Learning and Improvement

Keyword(s): Non-Pain Symptoms and Syndromes