Jatoi, A., Rowland, K., Loprinzi, C.L., Sloan, J.A., Dakhil, S.R., MacDonald, N., . . . Christensen, B. (2004). An eicosapentaenoic acid supplement versus megestrol acetate versus both for patients with cancer associated wasting: A North Central Cancer Treatment Group and National Cancer Institute of Canada collaborative effort. Journal of Clinical Oncology, 22, 2469–2476.

To evaluate the efficacy of ecosapentaenoic acid (EPA) supplement plus placebo versus megestrol acetate plus placebo supplement versus combination of both EPA supplement and megestrol

The EPA dose was 1.09 g BID in supplement plus liquid placebo. The megesterol acetate dose was 600 mg/day plus placebo supplement BID. The combination dose was EPA 1.09 g supplement BID plus megesterol acetate 600 mg/day. Patients were stratified and randomized to one of three treatment arms. Median number of days on study was relatively equal for all three arms at slightly more than three months. Megesterol acetate served as the control arm secondary to its proven efficacy.

• The study reported on 421 patients.
• Inclusion was based on age 18 years or older with incurable malignancy other than brain, breast, ovarian, prostate, or endometrial cancer; life expectancy of three months or more; Eastern Cooperative Oncology Group performance status of 2 or better; and self-reported two-month weight loss of five or more pounds and/or physician-estimated daily intake of less than 20 calories/kg/day.
• All patients had to perceive that weight loss was a problem, and the physicians had to view weight gain as a beneficial outcome.
• Exclusion criteria other than previously listed tumor types were use of tube feedings or parenteral nutrition; edema or ascites; use of adrenal steroids (other than short-term dexamethasone with chemotherapy), androgens, progestational agents, or other appetite stimulants within the past month; brain metastases; insulin-requiring diabetes; pregnancy; lactation; poorly controlled hypertension or congestive heart failure; history of thromboembolism; and obstruction in alimentary tract, malabsorption, or intractable vomiting.

The study was a collaborative effort of the North Central Cancer Treatment Group (NCCTG) and the National Cancer Institute of Canada, conducted at 26 primary treatment centers.

A double-blinded, randomized, three-armed trial design was used.

• Weight measured at MD’s office at baseline and monthly
• NCCTG questionnaire to measure appetite and weight loss at baseline, weekly, for four weeks, and then monthly 
• Functional Assessment of Anorexia/Cachexia Therapy (FAACT) administered at same intervals as above
• Single-item uniscale question to measure global quality of life administered at same intervals as above

The primary endpoint was weight gain of 10% or more (chosen because of previously proven efficacy of megesterol acetate). Among the three arms, 6% of patients achieved this in the EPA arm, 18% in the megesterol arm, and 11% in the combination arm. There was a p value of 0.01 showing greater efficacy with single-agent megesterol acetate. Appetite results using the NCCTG questionnaire were comparable for all three groups, showing varying degrees of favorable effects in all treatment arms. Appetite results using FAACT showed that the megesterol acetate and combination arms provided better appetite stimulation than EPA alone: 40 for EPA, 55 for megesterol acetate, and 55 for combination.

There was no significant difference for survival times or quality of life between the three arms. Recommendation of authors is not to use EPA alone or in combination.

Sample size was very good, and statistical analysis was very thorough.

• The study did not include a true placebo arm; therefore, the orexigenic effects of EPA cannot be determined but rather only suggested since there was an equivalent result on the NCCTG questionnaire when compared to megesterol acetate.
• No definition of anorexia was provided.