Goss P E, Gwyn K M
Department of Hematology/Oncology, Toronto Hospital--General Division, Canada.
J Clin Oncol. 1994 Nov;12(11):2460-70. doi: 10.1200/JCO.1994.12.11.2460.
One way to deprive hormone-dependent breast cancer of estrogen is to prevent its synthesis. This is achievable by inhibiting the aromatase cytochrome P-450 (P-450arom) enzyme complex responsible for the ultimate step in estrogen production. A new generation of specific and selective aromatase inhibitors is currently under investigation. The purpose of this review is to outline the preclinical test systems for screening these inhibitors, to summarize the preclinical and clinical data published to date, and to discuss the future application of these inhibitors in the management of breast cancer.
Disadvantages to the use of earlier inhibitors are described. In vitro and in vivo experiments that reflect the potency and selectivity of new inhibitors are highlighted. From preliminary clinical trials, these inhibitors appear to have excellent pharmacokinetic profiles and produce few side effects when administered orally. Activity against postmenopausal metastatic breast cancer has been demonstrated for the agents reviewed. They are all now in phase III testing to determine their relative efficacy in this setting. Their application in combination with both hormone therapy and chemotherapy, in premenopausal metastatic disease, and in the adjuvant setting in both premenopausal and postmenopausal women remains to be defined.
剥夺激素依赖性乳腺癌雌激素的一种方法是阻止其合成。这可以通过抑制负责雌激素生成最终步骤的芳香化酶细胞色素P - 450（P - 450arom）酶复合物来实现。新一代特异性和选择性芳香化酶抑制剂目前正在研究中。本综述的目的是概述用于筛选这些抑制剂的临床前测试系统，总结迄今为止已发表的临床前和临床数据，并讨论这些抑制剂在乳腺癌治疗中的未来应用。
描述了使用早期抑制剂的缺点。重点介绍了反映新抑制剂效力和选择性的体外和体内实验。从初步临床试验来看，这些抑制剂似乎具有出色的药代动力学特征，口服给药时副作用很少。已证明所审查的药物对绝经后转移性乳腺癌有活性。它们目前都处于III期试验阶段，以确定它们在这种情况下的相对疗效。它们在绝经前转移性疾病以及绝经前和绝经后妇女的辅助治疗中与激素疗法和化疗联合应用的情况仍有待确定。
