Nelson, K.A., Walsh, D., & Hussein, M. (2002). A phase II study of low-dose megestrol acetate using twice-daily dosing for anorexia in nonhormonally dependent cancer. American Journal of Hospice and Palliative Care, 19, 206–210.

To evaluate the efficacy of a low dose of megestrol acetate (MA) in debilitated patients with cancer experiencing cachexia

Participants received 80 mg of MA twice daily after meals. After a two-week treatment period, participants were evaluated for efficacy, side effects, and satisfaction.

Consecutive patients (convenience sample)

Patients with advanced cancer and any degree of weight loss were eligible for the study. Of the 20 patients who were evaluable,

• 12 were female and 8 were male.
• The median age was 68.
• The most common malignancy was lung cancer.
• The median ECOG performance status was 2.

Excluded from the study were patients with

• A life expectancy of less than four weeks
• An ECOG performance status of less than 3
• Breast or prostate cancer who were currently receiving hormonal or cytotoxic therapy
• The presence of pleural effusion or ascites
• Uncontrolled hypertension, diabetes mellitus, or congestive heart failure 
• A history of deep-vein thrombosis (DVT) or in treatment for DVT.

This single-site study took place in a large midwestern city at a large academic medical center with a cancer center.

The study was a phase II trial with a nonrandomized design and a descriptive, observational setup.

Outcomes included appetite, satisfaction, and side effects. Appetite and satisfaction were evaluated using a questionnaire that included one question for appetite (0 = absent, 4 = better than normal) and one yes/no question on satisfaction (Are you satisfied with the way the medication affected your appetite?). This empirical indicator appears to have been developed by the research team, although this is not clearly explicated. Side effects were measured using a “Side Effect Profile” (a list of MA side effects developed from a number of previous studies using varying doses of MA).

Fifteen out of 20 patients were deemed “responders.” Most responders had an appetite change of one degree in the categorical question, and 16 answered that they were “satisfied” with the way the medication affected their appetite. There were no significant differences in results based on gender, age, or performance status. The third outcome, side effects, was not specifically reported according to the Side Effect Profile. Researchers reported that five patients developed symptoms not present before the study; in three patients, these were considered drug-related.

The researchers concluded that a low dose of MA given twice daily was an effective appetite stimulant in patients with advanced cancer.

• The study lacked a constitutive definition of anorexia, appetite, satisfaction, and side effects. 
• Participants were considered evaluable for side effects after two doses and for efficacy after four doses. This time period (1 to 2 days) does not allow time for the drug to take effect.
• Eligibility criteria lack specificity.
• The validity and reliability of the instrument used to measure appetite and satisfaction are absent.
• Researchers indicated that appetite improvement by one degree on the categorical scale was a response, but how or why one degree constituted a response was not specified.
• The recruitment sites were listed, but these settings were not described.
• The statistical discussion was weak, with no explanation of sample-size calculation, power, or effect size.
• There was limited discussion of the statistical methods used to assess outcomes.
• Cost implications were not discussed.