Early ReportVenlafaxine in management of hot flashes in survivors of breast cancer: a randomised controlled trial
Introduction
Hot flashes are a substantial problem in menopausal women. Oestrogen therapy is the mainstay of treatment for this symptom and generally controls hot flashes well.
Hot flashes may be more troublesome in women who have survived breast cancer1, 2 than in other women for several reasons. First, many women treated for breast cancer when premenopausal undergo premature menopause from chemotherapy. Second, many survivors of breast cancer are given tamoxifen, the most prevalent side-effect of which is hot flashes. Third, women with a history of breast cancer have generally been denied oestrogen therapy, at least in North America, because of concerns about potentiating recurrence of breast cancer.
Many agents have been investigated as potential means for alleviating hot flashes in survivors of breast cancer. The best-described non-oestrogenic treatments for hot flashes are progestagens. For example, low doses of megestrol acetate result in a reduction of about 80% in hot flashes, compared with a decrease of about 20% with placebo.3 At present, there are no convincing data that megestrol acetate has any substantial positive or negative effect on breast-cancer morbidity or mortality. Therefore, this therapy can reasonably be used after a thorough discussion of potential risks and benefits with the patient. Nonetheless, some patients and physicians are concerned about the use of any hormone in survivors of breast cancer. Thus, non-hormonal means to alleviate hot flashes in these patients are needed. Various non-hormonal therapies, including vitamin E, clonidine, Bellergal (phenobarbital, ergotamine, and levorotatory alkaloids of belladonna), and methyldopa, have been examined4, 5, 6, 7 but have limited efficacy or adverse side-effects.
On the basis of positive anecdotal experience, we undertook a pilot study of the antidepressant venlafaxine in cancer patients with hot flashes. The results supported the anecdotal experience.8, 9
We undertook this study to assess more definitively the efficacy and toxicity of various doses of venlafaxine for the treatment of hot flashes in survivors of breast cancer. The hypothesis was that venlafaxine would be effective in alleviating hot-flash activity. Planned subgroup analyses included an investigation into whether there was a dose-response relation, with control for potential confounding (mood change and quality of life).
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Patients
Patients eligible for this trial were women who had a history of breast cancer or who were concerned about taking oestrogen for fear of breast cancer. Inclusion criteria were: troublesome hot flashes, occurring at least 14 times per week; flashes severe enough for the patient to desire therapeutic intervention, and present for at least a month before study entry; age older than 18 years; life expectancy at least 6 months; and performance status of 0–1 on the Eastern Cooperative Oncology Group
Results
229 patients joined this study between Feb 22 and July 27, 1999 (figure 1). Seven patients withdrew before taking any study medication and one patient was found to be ineligible. Hot-flash data for the baseline week were available for 207 patients (94%) and evaluable data over the whole study period for 191 (86%). The 30 patients who did not provide usable hot-flash data had stopped the study medications, did not properly complete or return the diary forms, or both.
At study entry the four
Discussion
This trial suggests that venlafaxine can alleviate hot flashes and that the most appropriate dose for this indication is 75 mg daily, which was more effective than 37·5 mg daily but was as effective as, and less toxic than, the 150mg dose. Thus, we recommend that treatment should start with a daily dose of 37·5 mg and be increased if necessary to 75 mg, but not higher. Some patients had substantial decreases in hot-flash activity with 37·5 mg venlafaxine daily. For those patients, there may not
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