Buzdar A, Howell A, Cuzick J, Wale C, Distler W, Hoctin-Boes G, Houghton J, Locker G Y, Nabholtz J M
University of Texas, MD Anderson Cancer Center, Houston, TX, USA.
Lancet Oncol. 2006 Aug;7(8):633-43. doi: 10.1016/S1470-2045(06)70767-7.
The Arimidex (anastrozole), Tamoxifen, Alone or in Combination (ATAC) trial was designed to compare the efficacy and safety of anastrozole with tamoxifen as adjuvant treatment for postmenopausal women with early-stage breast cancer. After an extended follow-up beyond the 5 years of treatment, we aimed to assess the safety, tolerability, and risk-benefit indices of these compounds.
We analysed postmenopausal women (mean age 64 years [SD 9]) with localised breast cancer randomly assigned to anastrozole (n=3125) or tamoxifen (n=3116). Efficacy measures, including death and risk-benefit indices, were analysed by intention to treat. Safety analyses were based on treatment first received (n=3092 for anastrozole and n=3094 tamoxifen). We calculated a risk-benefit analysis using the two global indices for the Women's Health Initiative and for Disease-Free Survival and Serious Adverse Events. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN18233230.
At median follow-up of 68 months (range 1-93), treatment-related adverse events occurred significantly less often with anastrozole than with tamoxifen (1884 [61%] vs 2117 [68%]; p<0.0001), as did treatment-related serious adverse events (146 [5%] vs 277 [9%]; p<0.0001) and adverse events leading to withdrawal (344 [11%] vs 442 [14%]; p=0.0002). Patients given anastrozole had significantly fewer overall events for the Global Index of the Women's Health Initiative (744 [24%] vs 851 [27%]; hazard ratio 0.85 [95% CI 0.77-0.94], p=0.001) and the Global Index of Disease-Free Survival and Serious Adverse Events (1453 [46%] vs 1594 [51%]; 0.88 [0.82-0.94]; p=0.0004).
Anastrozole is tolerated better than tamoxifen by postmenopausal women with early-stage breast cancer, and results in fewer serious adverse events. Furthermore, it has a more favourable overall risk-benefit profile and lower recurrence rate than tamoxifen.
阿那曲唑、他莫昔芬单药或联合用药（ATAC）试验旨在比较阿那曲唑与他莫昔芬作为绝经后早期乳腺癌辅助治疗的疗效和安全性。在5年治疗期进行延长随访后，我们旨在评估这些药物的安全性、耐受性和风险效益指数。
我们分析了随机分配接受阿那曲唑（n = 3125）或他莫昔芬（n = 3116）治疗的绝经后局部乳腺癌妇女（平均年龄64岁[标准差9]）。通过意向性分析评估包括死亡和风险效益指数在内的疗效指标。安全性分析基于首次接受的治疗（阿那曲唑组n = 3092，他莫昔芬组n = 3094）。我们使用妇女健康倡议和无病生存及严重不良事件的两个综合指数进行了风险效益分析。本研究已注册为国际标准随机对照试验，编号ISRCTN18233230。
在中位随访68个月（范围1 - 93个月）时，阿那曲唑治疗相关不良事件的发生频率显著低于他莫昔芬（1884例[61%]对2117例[68%]；p < 0.0001），治疗相关严重不良事件（146例[5%]对277例[9%]；p < 0.0001）以及导致停药的不良事件（344例[11%]对442例[14%]；p = 0.0002）也是如此。接受阿那曲唑治疗的患者在妇女健康倡议综合指数（744例[24%]对851例[27%]；风险比0.85[95%置信区间0.77 - 0.94]，p = 0.001）和无病生存及严重不良事件综合指数（1453例[46%]对1594例[51%]；0.88[0.82 - 0.94]；p = 0.0004）方面的总体事件显著更少。
对于绝经后早期乳腺癌妇女，阿那曲唑的耐受性优于他莫昔芬，且严重不良事件更少。此外，与他莫昔芬相比，它具有更有利的总体风险效益概况和更低的复发率。
