Buzdar A, Douma J, Davidson N, Elledge R, Morgan M, Smith R, Porter L, Nabholtz J, Xiang X, Brady C
University of Texas M.D. Anderson Cancer Center and Baylor College of Medicine, Houston, TX, USA.
J Clin Oncol. 2001 Jul 15;19(14):3357-66. doi: 10.1200/JCO.2001.19.14.3357.
To compare two doses of letrozole (0.5 mg and 2.5 mg every day) and megestrol acetate (40 mg qid) as endocrine therapy in postmenopausal women with advanced breast cancer previously treated with antiestrogens.
This double-blind, randomized, multicenter, multinational study enrolled 602 patients, all of whom were included in the primary analysis in the protocol. Patients had advanced or metastatic breast cancer with evidence of disease progression while receiving continuous adjuvant antiestrogen therapy, had experienced relapse within 12 months of stopping adjuvant antiestrogen therapy given for at least 6 months, or had experienced disease progression while receiving antiestrogen therapy for advanced disease. Tumors were required to be estrogen receptor- and/or progesterone receptor-positive or of unknown status. Confirmed objective response rate was the primary efficacy variable. Karnofsky Performance Status and European Organization for Research and Treatment of Cancer quality-of-life assessments were collected for 1 year.
There were no statistically significant differences among the three treatment groups for overall objective tumor response. Patients treated with letrozole 0.5 mg had improvements in disease progression (P =.044) and a decreased risk of treatment failure (P =.018), compared with patients treated with megestrol acetate. Letrozole 0.5 mg showed a trend (P =.053) for survival benefit when compared with megestrol acetate. Megestrol acetate was more likely to produce weight gain, dyspnea, and vaginal bleeding, and the letrozole groups were more likely to experience headache, hair thinning, and diarrhea.
Given a favorable tolerability profile, once-daily dosing, and evidence of clinically relevant benefit, letrozole is equivalent to megestrol acetate and should be considered for use as an alternative treatment of advanced breast cancer in postmenopausal women after treatment failure with antiestrogens.
比较两种剂量的来曲唑（每日0.5毫克和2.5毫克）与醋酸甲地孕酮（每日4次，每次40毫克）作为内分泌治疗药物，用于先前接受过抗雌激素治疗的绝经后晚期乳腺癌妇女。
这项双盲、随机、多中心、跨国研究纳入了602例患者，所有患者均按方案纳入主要分析。患者患有晚期或转移性乳腺癌，在接受持续辅助抗雌激素治疗时有疾病进展的证据，在停止至少6个月的辅助抗雌激素治疗后12个月内复发，或在接受晚期疾病抗雌激素治疗时有疾病进展。肿瘤需为雌激素受体和/或孕激素受体阳性或状态未知。确认的客观缓解率是主要疗效变量。收集卡氏功能状态评分和欧洲癌症研究与治疗组织的生活质量评估数据，为期1年。
三个治疗组在总体客观肿瘤反应方面无统计学显著差异。与接受醋酸甲地孕酮治疗的患者相比，接受0.5毫克来曲唑治疗的患者疾病进展有所改善（P = 0.044），治疗失败风险降低（P = 0.018）。与醋酸甲地孕酮相比，0.5毫克来曲唑显示出生存获益的趋势（P = 0.053）。醋酸甲地孕酮更易导致体重增加、呼吸困难和阴道出血，而来曲唑组更易出现头痛、头发稀疏和腹泻。
鉴于来曲唑具有良好的耐受性、每日一次给药以及临床相关获益的证据，它与醋酸甲地孕酮等效，在抗雌激素治疗失败后，应考虑将其作为绝经后晚期乳腺癌的替代治疗药物。
