Fast Fact and Concept #100: Megestrol Acetate for Cancer Anorexia Cachexia

Title: Fast Fact and Concept #100: Megestrol Acetate for Cancer Anorexia Cachexia

Author(s): Salacz, Mike

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., TPN) have demonstrated limited efficacy, at the price of increased morbidity. Megestrol acetate, a synthetic progestin, has been extensively studied as an appetite stimulant.

Clinical trials have demonstrated that megestrol is:

equally efficacious to dexamethasone as an appetite stimulant
superior to dronabinol (see FF #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 suggests 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 response duration of 6-8 weeks.

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 800mg/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 = $6.00/day

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:
Inui, A., Cancer Anorexia-Cachexia Syndrome: Current issues in research and management, CA Cancer J Clin 2002;52:72-91.
Jatoi, A., On appetite and its loss, Classic Papers, Supplement to JCO, Vol 21, No 9 (May 1), 2003: pp 79s-81s.
Jatoi, A., Dronabinol versus Megestrol Acetate versus Combination Therapy for Cancer-Associated Anorexia: A North Central Cancer Treatment Group Study, J Clin Oncol, Vol 20, No 2, (January 15), 2002: pp 567-573.
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.
Tisdale, M.J., Biology of Cachexia, Journal of the National Cancer Institute, Vol 89, No 23, December 3, 1997.

Copyright/Referencing Information: Users are free to download and distribute Fast Facts for educational purposes only. Citation for referencing. Salacz M. Fast Facts and Concepts #100 Megestrol acetate for cancer anorexia/cachexia. October 2003. End-of-Life Physician Education Resource Center www.eperc.mcw.edu.

Disclaimer: Fast Facts provide educational information, this information is not medical advice. Health care providers should exercise their own independent clinical judgment. Some Fast Fact information cites the use of a product in 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.

Creation Date: 10/2003

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