SAN FRANCISCOThe marijuana derivative dronabinol (Marinol) was significantly less effective than standard megestrol(Drug information on megestrol) acetate at improving appetite and inducing weight gain in patients with advanced cancer. The results of a North Central Cancer Treatment Group (NCCTG)/Mayo clinic study also showed that combining the two drugs was no better than giving megestrol alone.
"More than half of patients with advanced cancer suffer from loss of appetite," reported Mayo Clinic medical oncologist Aminah Jatoi, MD. "Dronabinol has been approved for treating anorexia and weight loss in AIDS patients, but in the doses we used in this study, it is less effective than treatment with megestrol acetate, and combination treatment provided nothing over and above what was seen with megestrol alone," Dr. Jatoi said.
Many anorectic cancer patients are not helped by megestrol, a synthetic progesterone(Drug information on progesterone) that sometimes causes uncomfortable side effects, especially in male patients. This study had looked to dronabinol as a potentially more effective alternative, but the results did not support that proposition.
This NCCTG study was the first randomized, double-blind trial to examine whether cannabinoids are comparable to established appetite stimulants in advanced anorectic cancer patients. Dr. Jatoi explained that the study was designed to determine whether dronabinol, administered alone or with megestrol acetate, was more, less, or equal in efficacy to single-agent megestrol acetate for palliating cancer-associated anorexia.
The phase III trial included 469 evaluable advanced cancer patients who were randomized to one of three arms:
• oral megestrol acetate 800 mg/day liquid suspension + tablet placebo (n = 159);
• oral dronabinol 2.5 mg BID + liquid placebo (n = 152); or
• both megestrol and dronabinol (n = 158).
Patients continued on treatment as long as they thought the treatment was helping them.
Members of the three different treatment groups were comparable at baseline in terms of age, gender, tumor type, weight loss, and performance status. Patients were eligible for the trial if they had loss of appetite or weight as a continuing problem and reported weight loss of 5 pounds over 2 months and/or a daily intake of < 20 calories/kg of body weight.
Megestrol acetate improved appetite in 73% of patients vs 47% of patients treated with dronabinol. This was associated with a 10% or greater weight gain in 13% of patients treated with megestrol acetate vs 5% treated with dronabinol (P = 0.009). Dr. Jatoi found that combination treatment resulted in no significant differences in appetite or weight compared to megestrol acetate alone.
The NCCTG investigators used the Functional Assessment of Cancer Therapy survey emphasizing anorexia-related questions, to examine the effect of each treatment on quality of life. They found that quality of life improved only in patients treated either with megestrol acetate alone or with both drugs, not in those treated with dronabinol alone. The single-item Uniscale, a more global quality of life assessment, found comparable scores between groups.
Toxicity was comparable between groups except that more men treated with megestrol acetate reported impotence.
"Based on these phase III data, we conclude that megestrol acetate is more effective than dronabinol at relieving anorexia in patients with advanced cancer," Dr. Jatoi concluded. "Combination therapy with both drugs confers no additional benefit over megestrol acetate alone."