Wakeling A E
Bioscience I, ICI Pharmaceuticals, Macclesfield, Cheshire, United Kingdom.
Breast Cancer Res Treat. 1993;25(1):1-9. doi: 10.1007/BF00662395.
The rationale for seeking to identify new pure antiestrogens was based on the recognition that existing antiestrogens, exemplified by tamoxifen, all possess partial agonist (estrogenic) activity. Conceptually, pure antiestrogens should be more effective than tamoxifen in ablating the mitogenic action of estrogens on breast tumor growth. The discovery and properties of the pure antiestrogens ICI 164,384 and ICI 182,780 are described and contrasted with those of tamoxifen. Key characteristics of these compounds which may be of particular relevance to their therapeutic application in the treatment of breast cancer are described. These include experimental data which predict efficacy in patients whose disease recurs during tamoxifen treatment, and the potential for pure antiestrogens to demonstrate greater efficacy than tamoxifen in first-line treatment of advanced breast cancer. The data imply that gains in efficacy could emerge as more rapid, more complete, or longer-lasting tumor remissions. Clinical trials with ICI 182,780 will reveal whether one or more of these predictions is correct.
寻求鉴定新型纯抗雌激素药物的基本原理是基于这样一种认识，即现有的抗雌激素药物（以他莫昔芬为代表）都具有部分激动剂（雌激素样）活性。从概念上讲，纯抗雌激素药物在消除雌激素对乳腺肿瘤生长的促有丝分裂作用方面应比他莫昔芬更有效。本文描述了纯抗雌激素药物ICI 164,384和ICI 182,780的发现及特性，并与他莫昔芬进行了对比。还描述了这些化合物的关键特性，这些特性可能与其在乳腺癌治疗中的治疗应用特别相关。其中包括预测在他莫昔芬治疗期间疾病复发患者疗效的实验数据，以及纯抗雌激素药物在晚期乳腺癌一线治疗中显示出比他莫昔芬更高疗效的可能性。这些数据表明，疗效的提高可能表现为更快速、更完全或更持久的肿瘤缓解。使用ICI 182,780的临床试验将揭示这些预测中的一个或多个是否正确。
