MEGESTROL ACETATE FOR GERIATRIC ANOREXIA/CACHEXIA

Abstract

To the Editor: In a Phase II randomized, controlled trial reported on in this Journal,1 the authors concluded that megestrol acetate suspension at doses of 200 mg, 400 mg, and 800 mg daily for 9 weeks had little effect on appetite, increased transthyretin (prealbumin) at the highest doses, and suppressed cortisol, with no effect on quality of life (although the study was not powered sufficiently to show an effect on this outcome). However, the major effect of megestrol acetate is an increase in body weight,2 and it was puzzling that the authors did not assess this outcome in this group of patients at 20, 42, and 63 days. Moreover, it is well established that megestrol acetate suspension is poorly absorbed in the absence of adequate food intake.3 In this sick group with fair or poor appetite, it is likely that drug absorption, and thus bioavailability, was not sufficient to show effects on the appetite outcomes. Recently, a new megestrol acetate preparation using NanoCrystal dispersion (NCD) technology (30 mg/mL) was shown to produce significantly greater absorption (121% greater area under the concentration time curve and 1,135% greater maximal plasma concentration) when taken in the fasting state than old megestrol acetate (40 mg/mL). A 90-mg/mL dose of the NCD formulation showed similar kinetics to the standard 40-mg/mL dose of the old formulation when taken with food.4 Moreover, the author's assessment of appetite may not be adequate and might be better assessed using validated assessment tools such as the Simplified Nutritional Appetite Questionnaire, which predicts weight loss and anorexia over a 6-month period with 84% specificity and sensitivity.5 The increase in serum prealbumin is important and has been shown by others to improve during megestrol acetate therapy in malnourished geriatric patients.6 One study reported increased prealbumin levels, increased food intake from 21% to 51% (P<.05) of a served meal, and increased BMI from 20.73 kg/m2 to 21.71 kg/m2 (P<.05) in geriatric patients after megestrol acetate.6 Suppression of serum cortisol levels is a well-recognized effect of megestrol acetate, which has adrenocorticoid properties similar to those of prednisone. From 1984 to 1996, Food and Drug Administration adverse drug experience reports identified five cases of Cushing's syndrome, 12 cases of new-onset hyperglycemia, 12 cases of exacerbation of preexisting diabetes mellitus, and 16 cases of adrenal insufficiency associated with megestrol acetate.7 As stated by the authors, this suppression did not result in any adrenal insufficiency–related adverse events, which appears to be the case in the majority of patients treated with megestrol acetate. This should not prevent the appropriate use of this drug.8 In conclusion, early-phase trials of megestrol acetate should incorporate assessment of body weight changes and transthyretin (prealbumin). The new NCD formulation should enhance the efficacy of treatment in anorexic geriatric patients through improved absorption of the drug in the fasting state. Financial Disclosure: The authors have no current financial support for research, consultantships, or speakers forums and no company holdings. Author Contributions: Matthew Haren, Moon Jong Kim, and Rafi Kevorkian all took part in the preparation of this manuscript. Sponsor's Role: Not applicable.