NEWS

Nonhormonal Agents Show Promise Against Hot Flashes

Nicole Gottlieb

Breast cancer survivors who experience debilitating hot flashes now have a new remedy: venlafaxine (Effexor), a drug used as an antidepressant. Charles Loprinzi, M.D., of the Mayo Clinic Cancer Center in Rochester, Minn., presented his results in May at the annual meeting of the American Society of Clinical Oncology, concluding that venlafaxine at 75 mg per day reduces hot flashes in breast cancer patients by approximately 60% from baseline. This 60% reduction is in a hot flash "score" that accounts for both the frequency and severity of hot flashes.



View larger version (131K):
[in this window]
[in a new window]
 
Dr. Charles Loprinzi

 
The 75 mg dose gave the best ratio of benefits to side effects, Loprinzi said; 150 mg—the dose typically used to treat depression—elevated side effects without increasing venlafaxine’s efficacy against hot flashes. At the 75 mg dose, a minority of patients experienced decreased appetite, nausea, and mouth dryness. Contrary to studies using other antidepressants against hot flashes, decreased libido was not a reported side effect.

"Hot flashes represent a major clinical problem for many postmenopausal women," said Loprinzi. "They are particularly problematic for patients with breast cancer for two reasons. First, the treatment of breast cancer can cause hot flashes and, second, estrogen is generally contraindicated and thus not oftentimes utilized in patients to treat these hot flashes."

Loprinzi’s finding adds further evidence for the benefit of nonhormonal therapies in the treatment of hot flashes. Other studies, with varying results, have examined the use of a blood pressure medication, vitamin E, soy products, and selective serotonin reuptake inhibitors (SSRIs), a relatively new class of antidepressant drugs. Venlafaxine itself blocks the reuptake of both norepinephrine and serotonin.

Although the pathophysiology of hot flashes remains unclear, the symptoms included in the term are well documented: a sensation of heat, sweating, flushing, dizziness, palpitations, irritability, anxiety, and/or panic. Some experts estimate that about 50% of breast cancer survivors list hot flashes as a prominent complaint.

Hormone replacement therapy such as estrogen helps to control hot flashes in menopausal women. But the concern that HRT—including the progestin therapy megestrol acetate—might increase the risk of developing a recurrence or a new breast cancer led researchers to search for other, nonhormonal means of reducing the frequency, severity, or duration of hot flashes.

Blood Pressure Medications

Studies examining the use of blood pressure medications in combating troublesome hot flashes date back to the early 1980s. In 1982, Larry R. Laufer, M.D., and his colleagues at the University of California, San Diego, concluded that the hypertension medication clonidine reduced the frequency of hot flashes in postmenopausal women by 46% from baseline.

Almost 20 years later, researchers continue to explore clonidine as a means to reduce hot flashes. Kishan Pandya, M.D., and his team of researchers at the University of Rochester Cancer Center Community Clinical Oncology Program Research Base, in Rochester, New York, also presented findings on the reduction of hot flashes at the ASCO meeting. Pandya et al. reported that after 8 weeks of treatment with oral clonidine at 0.1 mg per day, breast cancer patients experiencing tamoxifen-induced hot flashes had a mean decrease in hot flash frequency of 38%, compared with a decrease of 24% in the placebo group.



View larger version (113K):
[in this window]
[in a new window]
 
Dr. Kishan Pandya

 
"For menopausal symptoms, the effectiveness of clonidine has been established for the last 20 years," said Pandya. "But no one had actually looked at it for the treatment of tamoxifen-induced hot flashes. . . . We now have a drug that not only has some beneficial effects in control of hot flashes, but also has very few, if any, side effects as reported in our patient population."

Contrary to some physicians’ reports of adverse reactions such as dizziness or fainting, Pandya said that the only side effect in his study that was found to be statistically significantly different from placebo was difficulty sleeping. He also noted that some patients prefer to try clonidine for their hot flashes because of the possible stigmatization associated with taking an antidepressant.

SSRIs ‘Most Promising’

Studies of vitamin E and soy products, according to Loprinzi and other researchers, have shown them to be only marginally better than placebo. "It is the newer class of antidepressants, the SSRIs, that are the most promising non-estrogenic drugs to date for hot flashes," he said.

The SSRI class of drugs includes fluoxetine (Prozac) and paroxetine (Paxil), among others. Recent pilot tests of these antidepressant drugs to reduce hot flashes have shown positive results.

Vered Stearns, M.D., and her colleagues at the Georgetown University Medical Center, Washington, D.C., found in a pilot trial of 30 women that 20 mg daily of paroxetine led to a mean reduction in hot flash frequency of 67%. The mean reduction in hot flash severity was 75%. With a low occurrence of adverse effects, somnolence being the most common, 25 (83%) of the study participants chose to continue therapy after study termination. A placebo-controlled trial is under way.

"Many times before this trial," said Stearns, "we would spend the whole visit with many of our breast cancer survivors trying to figure out what to try next. But my colleagues and I have found that the women who take paroxetine and have reduction of hot flashes are very satisfied and really do not have a lot of side effects from the drug. So I think that on a scale of what’s available, it’s a very good option."

Loprinzi presented results of a study using fluoxetine at the 1999 annual San Antonio Breast Cancer Symposium. In his early analysis of a placebo-controlled trial, he found that Prozac showed an effect similar to that of venlafaxine in reducing hot flashes.

As the choice of therapies to combat troublesome hot flashes broadens, questions remain as to the optimal agent, dose, and duration of treatment, as well as the mechanisms of action. These questions also extend to men, who may experience hot flashes due to androgen ablation, a common treatment for prostate cancer. A small number of studies have found that sertraline (Zoloft), an SSRI, and venlafaxine may also relieve hot flashes in men.

"The field of hot flashes is one that’s really suddenly exploding," said Pandya. "There’s a lot of interest in finding newer and better agents for this very disturbing symptom."

Go


View this table:
[in this window]
[in a new window]
 
Therapies for Hot Flashes in Breast Cancer Survivors
 



             
Copyright © 2000 Oxford University Press (unless otherwise stated)
Oxford University Press Privacy Policy and Legal Statement