VENLAFAXINE FOR HOT FLASHES FOLLOWING BREAST CANCER

潮热是乳腺癌妇女报告的最严重和第四大流行的更年期症状。 潮热影响了超过65%的这一人群，59%的人认为症状严重，44%的人报告他们对症状感到非常痛苦。 尽管与此症状相关的高患病率，严重程度和痛苦，但管理乳腺癌女性潮热的科学依据有限。 这项随机、双盲、安慰剂对照的交叉试验考察了缓释盐酸文拉法辛（37.5 mg po qd）对乳腺癌治疗后女性潮热的有效性和毒性。 文拉法辛是一种苯乙胺衍生物，可有效抑制神经元5-羟色胺和去甲肾上腺素的再摄取，并微弱抑制多巴胺的再摄取。 该项目的第二个目的是检查潮热对心理，行为和身体结果的影响。这项研究是基于威克姆症状管理模式，其中描述了症状，症状管理策略和症状管理结果之间的相互关系。 参与者（n = 80）完成手术、放疗和/或化疗后至少一个月，并且已经服用他莫昔芬（如果处方）至少6周，将完成为期2周的基线潮热评估，并随机分配至交叉试验的一个组。 在第一个6周组结束时，受试者将交叉至另一个研究组，再持续6周。 待评估的结局包括干预的有效性（潮热频率、严重程度、痛苦和程度）、干预的毒性（主观偏好、副作用）、心理结局（情绪障碍）、行为结局（生活质量、日常活动干扰）和身体结局（疲劳和睡眠障碍）。 将使用主观、前瞻性日记方法每天测量潮热，并使用胸骨皮肤电导的客观最新24小时生理监测每周测量潮热。 其他成果将每周衡量一次。 每周使用药物泡罩包装卡评估干预/安慰剂依从性。 结局评估的时间基于生理监测器械的局限性和治疗效果的预期时间。汇总统计（即，平均值、斜率、最大响应、范围、比例、可实现的差异）将用于有效地将设计简化为2 × 2交叉，并相应地分析数据（即，t检验、线性回归、GEE、混合模型）。研究结果将为乳腺癌治疗后女性潮热管理的科学基础做出重大贡献。

Hot flashes are the most severe and fourth most prevalent menopausal symptom reported by women with breast cancer. Hot flashes affect over 65 percent of this population, with 59 percent rating the symptom as severe and 44 percent reporting they are extremely distressed by the symptom. Despite the high prevalence, severity and distress associated with this symptom, the scientific basis for managing hot flashes in women with breast cancer is limited. This randomized, double-blind, placebo-controlled crossover trial examines the effectiveness and toxicity of sustained release venlafaxine hydrochloride (37.5 mg po qd) on hot flashes in women following treatment for breast cancer. Venlafaxine is a phenylethylamine derivative that potently inhibits the reuptake of neuronal serotonin and norepinephrine and weakly inhibits the reuptake of dopamine. A secondary aim of this project is to examine the impact of hot flashes on psychological, behavioral, and physical outcomes. This study is based on the Wickham Symptom Management Model which depicts interrelationships between symptoms, symptom management strategies, and symptom management outcomes. Participants (n = 80) who are at least one month post-completion of surgery, radiation, and/or chemotherapy and who have been on tamoxifen (if prescribed) for at least 6 weeks will complete a 2-week baseline hot flash assessment and be randomized to one arm of the crossover trial. At the end of the first 6-week arm, participants will crossover to the opposite study arm for an additional 6 weeks. Outcomes to be assessed include effectiveness of the intervention (hot flash frequency, severity, distress and magnitude), toxicity of the intervention (subjective preference, side effects), psychological outcomes (mood disturbance), behavioral outcomes (quality of life, interference with daily activities) and physical outcomes (fatigue and sleep disturbance). Hot flashes will be measured daily, using a subjective, prospective diary methodology, and weekly, using objective state-of-the art 24-hour physiological monitoring of sternal skin conductance. Other outcomes will be measured weekly. Compliance with the intervention/placebo will be assessed weekly using medication blister pack cards. Timing of outcome assessments is based on limitations of the physiological monitoring device and expected timing of treatment effects. Summary statistics (i.e., mean, slope, maximum response, range, proportion, achievable difference) will be used to effectively reduce the design to a 2 X 2 crossover and data will be analyzed accordingly (i.e., t-tests, linear regression, GEE, mixed model). Study findings will significantly contribute to the scientific basis of hot flash management in women following treatment for breast cancer.