Venlafaxine, Clonidine Top Placebo for Breast Cancer Hot Flashes

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Small Numbers Mar Findings

The main weakness of this study was that "the patient numbers were too small to reliably identify suspected differences between the two active study arms," said Dr. Charles L. Loprinzi, Dr. Debra L. Barton, and Dr. Rui Qin.

The unbalanced randomization scheme and the unequal dropout rates, which likely were due to perceived toxicities, meant that only 35 patients were available for analysis in the venlafaxine group, 28 in the clonidine group, and 17 in the placebo group. To detect a 10% difference between the two active drugs, 156 subjects would have been needed per study arm, and to detect a 5% difference, 620 would have been needed. "With the currently reported sample size ... the power of detecting a 10% difference is only 29%," they noted.

For clinicians, they added, available data suggest multiple nonestrogenic options are available for treating hot flashes. "Our suggestion is that these nonhormonal options be tried in the order in which they are listed (an antidepressant, then an antiseizure medication, then clonidine), unless there are contraindications to particular drugs in individual patients," they wrote.

Dr. Loprinzi, Dr. Barton, and Dr. Qin are at the Mayo Clinic in Rochester, Minn. Dr. Loprinzi reported ties to Pfizer. These remarks were taken from their editorial accompanying Dr. Boekhout’s report (J. Clin. Oncol. 2011 Sept. 12 [doi:10.120o/JCO.2011.37.5865]).



Venlafaxine and clonidine both outperformed placebo in controlling hot flashes among women with breast cancer in a study published online Sept. 12 in the Journal of Clinical Oncology.

Effective treatments for hot flashes may improve these patients’ ability to continue their anticancer therapies, said Dr. Annelies H. Boekhout of The Netherlands Cancer Institute, Amsterdam, and her associates.

The SSNRI venlafaxine (Effexor) and the antihypertensive clonidine "both are often prescribed treatments and are recommended in clinical guidelines in the management of hot flashes. However, a three-arm trial comparing clonidine, venlafaxine, and placebo in patients with breast cancer has not been conducted" until now, they noted.

In their double-blind study at three Dutch hospitals, 102 women with breast cancer who experienced at least two hot flashes per day were stratified by age, duration of symptoms, concurrent endocrine therapy, and previous chemotherapy, and randomly assigned to receive 75 mg venlafaxine (41 patients), 0.1 mg clonidine (41 patients), or matching placebo (20 patients) daily for 12 weeks.

The women completed daily diaries recording the frequency and severity of hot flashes. They also reported every week on adverse events such as reduced appetite, nausea, sleepiness, dizziness, fatigue, dry mouth, and constipation. They recorded their sleep quality, anxiety, depression, and sexual function at 4 weeks and at the conclusion of treatment.

A total of 22 subjects (22%) either dropped out of the study or were lost to follow-up. Two patients (5%) in the venlafaxine group and six (15%) in the clonidine group cited adverse effects such as somnolence, dizziness, and dry mouth as their reason for discontinuing. Another 9% of patients discontinued because of noncompliance, which "had some effect on the observed differences between treatments in this study."

Among the 35 women assigned to venlafaxine who completed the trial, there was a 42% decline in hot flashes during weeks 1-4, compared with the placebo group. Over the entire study period, the reduction in hot flashes was 41% with venlafaxine, compared with placebo.

Among the 28 women assigned to clonidine who completed the trial, hot flashes declined by only 26% during weeks 1-4 but then declined another 22% during the remainder of the study, for an overall reduction of approximately 45%.

Thus, both active agents decreased the frequency and severity of hot flashes compared with placebo, with no discernible difference between the two by week 12. "A more rapid reduction of hot flashes suggests that venlafaxine is to be preferred over clonidine," Dr. Boekhout and her colleagues said (J. Clin. Oncol. 2011 Sept. 12 [doi:10.1200/JCO.2010.33.1298]).

They added that it is "advisable to treat patients to manage hot flashes with venlafaxine 37.5 mg daily in the first week and increase the venlafaxine dose to 75 mg if greater efficacy is desired."

A total of 14 patients (34%) in the clonidine group, 23 (56%) in the venlafaxine group, and 4 (20%) in the placebo group said they wished to continue the study treatment at the end of the trial.

Women taking clonidine reported more symptoms of anxiety and women taking venlafaxine reported more symptoms of depression. Sexual function and sleep quality did not differ between the two groups. However, the duration of this study may have been too short to adequately assess these adverse effects, the researchers noted.

No conflicts of interest were reported.

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