LaVasseur, Beth

PURPOSE: In the course of conducting a series of prospective clinical trials devoted to defining new treatment opportunities for hot flashes in cancer survivors, considerable experience has been acquired with related methodologic issues. This article has been written in response to many queries regarding this methodology. PATIENTS AND METHODS: A series of seven different clinical trials that involved 968 patients was used for this work. Reliable and valid definitions of hot flash intensity were developed from patient-reported descriptions. Concomitant validity and reliability assessment of patient-completed diaries was undertaken to compare hot flash data with toxicity and quality-of-life (QOL) end points and to examine consistency across patient groups using variability analysis and correlation procedures. Parametric data from this meta-analysis was used to examine relative power considerations for the design of phase II and phase III clinical trials. RESULTS: Daily diaries used in these studies exhibited consistency and reliability and had few missing data. Hot flash frequency and hot flash score (frequency multiplied by average severity) variables produced almost identical end point results. For phase III placebo-controlled studies, 50 patients per treatment arm seem appropriate to provide sufficient power specifications to detect a clinically meaningful change in hot flash activity. For phase II trials, 25 patients per trial seem to provide reasonable estimates of eventual hot flash efficacy to screen potential agents for more definitive testing. CONCLUSION: Given the data gained from these experiences, we can plan and carry out more efficient trials to identify efficacious agents for the reduction of hot flash activity.

PURPOSE: Hot flashes represent a significant clinical problem for some breast cancer survivors. Safe, effective treatment is needed for this prominent clinical problem. Although it has been shown that estrogen or progesterone replacement therapy can alleviate this problem, there are continued safety concerns regarding the use of hormonal therapies in these women. Based on anecdotal information, we hypothesized that soy-derived phytoestrogens, weak estrogen-like substances in the soybean that demonstrate estrogen agonist and/or antagonist effects when they bind to estrogen receptors, could alleviate hot flashes. This current trial was designed to investigate this hypothesis.PATIENTS AND METHODS: This double-blind clinical trial involved breast cancer survivors with substantial hot flashes. After randomization, patients underwent a 1-week baseline period with no therapy. This was followed by 4 weeks of either soy tablets or placebo. The patients then crossed over to the opposite arm in a double-blind manner for the last 4 weeks. Patients completed a daily questionnaire documenting hot flash frequency, intensity, and perceived side effects.RESULTS: Of the 177 women who were randomized and started the study substance, 155 (88%) provided useable data over the first 5 weeks; 149 provided usable data over the entire 9 weeks. There was no suggestion that the soy product was more effective in reducing hot flashes than the placebo. At study completion, patients preferred the soy product 33% of the time, the placebo 37% of the time, and neither substance 31% of the time. No toxicity was observed.CONCLUSION: The soy product did not alleviate hot flashes in breast cancer survivors.

Purpose Up to 75% of women experience hot flashes, which can negatively impact quality of life. As hot flash physiology is not definitively understood, it cannot be assumed that effective agents represent class effects. Therefore, there is a continued need for rigorous evaluation to identify effective nonhormonal options for hot flash relief. Methods A randomized, double-blind trial evaluated citalopram at target doses of 10, 20, or 30 mg/d versus placebo for 6 weeks. Postmenopausal women with at least 14 bothersome hot flashes per week recorded hot flashes for 7 days before starting treatment and were then titrated to their target doses. The primary end point was the change from baseline to 6 weeks in hot flash score. Results Two hundred fifty-four women were randomly assigned onto this study. Data for hot flash scores and frequencies showed significant improvement in hot flashes with citalopram over placebo, with no significant differences among doses. Reductions in mean hot flash scores were 2.0 (23%), 7.0 (49%), 7.7 (50%), and 10.7 (55%) for placebo and 10, 20, and 30 mg of citalopram, respectively (P ≤ .002). Improvement in secondary outcomes, such as the Hot Flash Related Daily Interference Scale, was statistically superior in the 20-mg arm. Citalopram was well-tolerated, with no significant negative adverse effects. Conclusion Citalopram is an effective, well-tolerated agent in managing hot flashes. There does not appear to be a significant dose response above 10 mg/d, but broader helpful effects of the agent appear to be more evident at 20 mg/d.

Purpose Hot flashes can cause significant morbidity in postmenopausal women undergoing or finished with breast cancer treatment. Black cohosh has been used to treat hot flashes, but definitive clinical data about efficacy have been equivocal. Methods A double-blind, randomized, cross-over clinical trial with two 4-week periods, was used to study the efficacy of black cohosh (1 capsule, Cimicifuga racemosa 20 mg BID) for the treatment of hot flashes in women. Participants kept a daily hot flash diary during a baseline week and then during two 4-week crossover treatment periods. Hot flash scores were measured by assigning points (1 to 4 for mild to very severe) to each hot flash based on severity and then adding the points for a given time period. Results Between October 31, 2003, to March 4, 2004, 132 patients were randomly assigned. Toxicity was minimal and not different by treatment group. Patients receiving black cohosh reported a mean decrease in hot flash score of 20% (comparing the fourth treatment week to the baseline week) compared with a 27% decrease for patients on placebo (P = .53). Mean hot flash frequency was reduced 17% on black cohosh and 26% on placebo (P = .36). Patient treatment preferences were measured after completion of both treatment periods by ascertaining which treatment period, if any, the patient preferred. Thirty-four percent of patients preferred the black cohosh treatment, 38% preferred the placebo, and 28% did not prefer either treatment. Conclusion This trial failed to provide any evidence that black cohosh reduced hot flashes more than the placebo.