PURPOSE:Therapies for breast cancer may induce hot flashes that can affect quality of life. We undertook a double-blind, placebo-controlled trial with the primary objective of comparing the average daily hot flash scores in the twelfth week among patients treated with venlafaxine, clonidine, and placebo. Additional analyses of the hot flash score over the full 12 weeks of treatment were performed.PATIENTS AND METHODS:In all, 102 patients with a history of breast cancer were randomly assigned (2:2:1) to venlafaxine 75 mg, clonidine 0.1 mg, or placebo daily for 12 weeks. Questionnaires at baseline and during treatment assessed daily hot flash scores, sexual function, sleep quality, anxiety, and depression.RESULTS:After 12 weeks, a total of 80 patients were evaluable for the primary end point. During week 12, hot flash scores were significantly lower in the clonidine group versus placebo (P = .03); for venlafaxine versus placebo, the difference was borderline not significant (P = .07). However, hot flash scores were equal in the clonidine and venlafaxine groups. Over the course of 12 weeks, the differences between both treatments and placebo were significant (P <.001 for venlafaxine v placebo; P = .045 for clonidine v placebo). Frequencies of treatment-related adverse effects of nausea (P = .02), constipation (P = .04), and severe appetite loss were higher in the venlafaxine group.CONCLUSION:Venlafaxine and clonidine are effective treatments in the management of hot flashes in patients with breast cancer. Venlafaxine resulted in a more immediate reduction of hot flash scores when compared with clonidine; however, hot flash scores at week 12 were lower in the clonidine group than in the venlafaxine group.

Abstract Background: Therapies for breast cancer may result in symptoms as hot flashes, genitourinary atrophy and psychological distress. Hot flashes are common symptoms that can interfere with quality of life. We undertook a double-blind, placebo controlled trial to assess the efficacy of venlafaxine and clonidine during 12 weeks of treatment. Methods: 102 patients with a history of breast cancer with at least two hot flashes per day were randomly assigned (2:2:1) to venlafaxine 75 mg/d, clonidine 0.1 mg/d or placebo. Daily hot flash scores were recorded at baseline and during treatment. Questionnaires at baseline and during week 4 and 12 assessed sexual function (SAQ), sleep quality (GSQ), anxiety and depression (HADS). The primary endpoint was differences in the average daily hot flash score in the twelfth week between venlafaxine, clonidine and placebo. Secondary objectives were to determine the effect of both drugs on sexual function, sleep quality, anxiety, depression and treatment side effects. Analyses were by intention to treat. Results: 80 patients had evaluable data over the whole study period of 12 weeks. At week 12, treatment was associated with a decrease in the occurrence of hot flashes by 45% versus placebo (p=0.03). There was no significant difference between venlafaxine and clonidine treatment however, over the course of 12 weeks hot flash scores were reduced by 41% in the venlafaxine group and by 26% in the clonidine group (Figure 1). The differences between both treatments and placebo over the 12 week period were significant (p=0.0004 venlafaxine versus placebo, p=0.045 clonidine versus placebo, p=0.002 both treatments versus placebo). Sexual function and sleep quality were not significantly different between the two treatment groups. Adjusting for baseline scores, the week 12 anxiety scores were higher in the clonidine group than in the venlafaxine group (p=0.04) and the depression scores were higher in the venlafaxine group than in the clonidine group (p=0.03). Frequencies of treatment-related side effects, nausea (p=0.02) and constipation (p=0.04) were significantly higher in the venlafaxine group. Only appetite loss (p=0.003) occurred more frequently in the venlafaxine group as severe side effect. Premature discontinuation for adverse events occurred in 2 (5%) patients in the venlafaxine group and 6 (15%) patients in the clonidine group (p=0.26). 41 patients (40%) continued the study treatment after the end of the study. Figure 1. Hot flash score over 12 weeks (blue=placebo, red=clonidine, green=venlafaxine; Discussion: Venlafaxine and clonidine are effective treatments in the management of hot flashes. Venlafaxine treatment resulted in a swifter reduction in the hot flash score in comparison to clonidine. Venlafaxine is more effective than clonidine over the 12 week period of treatment, but at the cost of more side effects. These findings suggest that venlafaxine is to be preferred above clonidine. In case of intolerance clonidine is a realistic treatment alternative. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr PD08-04.