SAN FRANCISCOThe marijuana derivative dronabinol (Marinol)
was significantly less effective than standard 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.
Many anorectic cancer patients are not helped by megestrol, a
synthetic 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
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
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."