ORLANDO, FLA. — Venlafaxine controls hot flashes more effectively than clonidine, but not as well as a single dose of medroxyprogesterone acetate, according to randomized, controlled trials presented in posters at the annual meeting of the American Society of Clinical Oncology.
In a trial organized by the German Breast Group, venlafaxine (Effexor) reduced frequency of hot flashes by 62% and severity by 67% in breast cancer patients. Clonidine reduced frequency by 22% and severity by 48%, reported Sibylle Loibl, M.D.
In a North Central Cancer Treatment Group trial, venlafaxine reduced hot flash frequency by 52% and median hot flash scores by 57% in the first 185 patients evaluated. A single 400-mg dose of medroxyprogesterone (MPA, Depo-Provera) achieved an 85% drop in frequency and reduced scores by 88%, reported Charles L. Loprinzi, M.D.
MPA also had a better side effect profile than venlafaxine, but the North American trial did not address safety in women at risk for breast cancer.
“The bottom line is, it [MPA] clearly works better. I think it is a reasonable option to give,” Dr. Loprinzi, an oncologist at the Mayo Clinic, Rochester, Minn., said in an interview. “Whether is has a small effect on breast cancer risk of recurrence or developing or decrease is unknown.”
Dr. Loibl, a gynecologist in Neu-Isenburg, Germany, told this newspaper that the superiority of MPA was not surprising. “But we want to treat, especially breast cancer patients, without hormonal therapy,” she said, adding that she would consider it only if a woman has not gained relief after 4 weeks on venlafaxine.
The double-blind German trial randomized 80 breast cancer patients (median age 53) from April 2002 to October 2004, and was able to evaluate 69. All had at least two hot flashes per day at baseline. None used medication to treat hypertension or depression.
During the 5-week study, 34 patients took two 0.075-mg clonidine pills per day; 35 patients took venlafaxine in 37.5-mg pills, also twice a day. The primary end point was frequency of hot flashes at 5 weeks, but the researchers also reported that venlafaxine worked faster, reducing hot flashes significantly in the first week.
Side effects were comparable with both drugs and mostly occurred in the first week. Mouth dryness was the most common in both groups. Tiredness occurred in 25% of the clonidine group and 33% of patients on venlafaxine. About 25% of the venlafaxine patients experienced nausea, but Dr. Loibl said the incidence dropped nearly to zero after the first week.
Four patients stopped treatment early because of side effects, and seven disappeared from follow-up.
In the North American trial, almost two-thirds (63%) of the women had a history of breast cancer. The remaining 37% were afraid to take hormonal treatments because of breast cancer risk, according to Dr. Loprinzi.
All patients enrolled had at least 14 hot flashes a week. None were on antidepressants. Median age was in the mid-50s for all three arms of the 6-week study. The poster report on the study included data on a total of 195 patients.
One group of 94 patients started on a 37.5-mg daily dose of venlafaxine, which increased after 1 week to 75 mg. A second group of 94 patients received a single 400-mg dose of MPA.
A third group stopped accrual with seven patients because of enrollment difficulties. These patients received 500 mg of MPA every other week for 6 weeks. Their results were even better than the single-dose cohort, but their numbers were too small to compare meaningfully.
By the end of the trial, Dr. Loprinzi reported that 22 patients (24%) in the one-dose MPA arm were free of hot flashes compared with one patient (1%) on venlafaxine. In the MPA group, 90% reported residual hot flashes scores as 49% or less of baseline, compared with 63% of those on venlafaxine.
For the most part, MPA also was better tolerated, with patients reporting significantly less constipation, hot flash distress, abnormal sweating, and sleepiness, as well as significantly more satisfaction with hot flash control and trends toward less trouble with sleeping and orgasm.
“Based on efficacy, MPA wins. Based on acute toxicity, MPA wins. Based on cost, MPA is cheaper,” Dr. Loprinzi said, balancing the price of a single dose of MPA against daily treatment with venlafaxine.
Safety is the big unanswered question. The concern is whether MPA interferes with hormonal therapies such as tamoxifen and aromatase inhibitors, Dr. Loprinzi said.
“There is not a definitive answer,” he said. “You find circumstantial evidence on both sides of the fence.”