North Central Cancer Treatment Group researchers based at Mayo Clinic in Rochester, Minn., have discovered that low doses of a drug used to prevent epileptic seizures and to treat nerve pain caused by shingles substantially reduces hot flashes in patients who are undergoing anti-hormonal treatment, or androgen-deprivation therapy, for prostate cancer.
In presenting results of a 223-patient, placebo-controlled Phase III clinical trial at the 2007 annual meeting of the American Society of Clinical Oncology (http://www.asco.org/portal/site/ASCO), Mayo Clinic investigators report that the drug gabapentin reduced the frequency and the intensity of hot flashes by up to 46 percent in men receiving androgen deprivation therapy. The men who received gabapentin reported fewer side effects than those receiving a placebo tablet, the researchers say.
Many men undergoing androgen deprivation therapy suffer debilitating hot flashes, but until now the only therapeutic agents proven to provide relief are androgen-originating hormones, some of which can actually fuel their cancer. So any symptom relief these men get comes with worry about new cancer growth.
"To my knowledge, this is the first nonhormonal treatment of hot flashes in men, where results from a placebo-controlled trial are positive enough to support that a nonhormonal medication can be used to help some of our patients," says the study's lead investigator, Mayo Clinic oncologist Charles Loprinzi, M.D.
He adds that hot flashes in patients receiving androgen-deprivation therapy can be quite severe. Overall, between 60 percent and 80 percent of these patients suffer from hot flashes, Dr. Loprinzi says, and in this clinical trial, about 40 percent of participants had hot flashes for longer than nine months and a similar percentage reported having at least 10 hot flashes a day.
Because gabapentin works on the central nervous system, its function may be similar to some antidepressants that are prescribed to reduce hot flashes in women entering menopause, he says. "But we don't understand exactly how any of these drugs work to reduce hot flashes," says Dr. Loprinzi.
Gabapentin (trade name Neurontin) was approved by the Food and Drug Administration to treat epileptic seizures in 1994, and pain from shingles in 2002.
The ability of gabapentin to reduce hot flashes was first detected when it was being used for other reasons. Since then, several clinical trials testing gabapentin in women found that a dose of about 900 milligrams a day decreased hot flashes by about half -- the same dose and a similar degree of effectiveness discovered in Dr. Loprinzi's clinical trial.
Men participating in this study had a mean age of 70, and suffered with hot flashes occurring at least 14 times a week. They were randomized into four groups. Over 28 days, one group was given placebo pills, another received a 300 mg/d (milligrams a day) tablet of gabapentin, a third group received an escalating dose of gabapentin that reached 600 mg/d, and the fourth group's dose reached 900 mg/d. The study was blinded: physicians and patients did not know which pills contained the active agent.