de Jong P C, Blijham G H
Department of Internal Medicine, St. Antonius Hospital, Nieuwegein, The Netherlands.
Neth J Med. 1999 Aug;55(2):50-8. doi: 10.1016/s0300-2977(99)00030-3.
Inhibition of the enzyme aromatase, the rate limiting step in estrogen production, is an effective endocrine treatment of advanced postmenopausal breast cancer. Recently, several new aromatase inhibitors have been developed to improve efficacy and reduce toxicity compared to the prototype aromatase inhibitor aminoglutethimide. Aromatase inhibitors can be divided into two types. The first are the non-steroidal inhibitors that have a mechanism of action similar to aminoglutethimide. The second are the steroidal inhibitors that function as a false substrate for aromatase. Of the non-steroidal aromatase inhibitors, two drugs, anastrozole and letrozole, have recently been registered for the second line endocrine treatment of advanced postmenopausal breast cancer after failure on tamoxifen. The phase III studies of these drugs indicate at least equal efficacy compared to current second line treatment with aminoglutethimide or megestrol acetate. Their toxicity profile, however, is much more favourable. This makes them the drugs of choice for the second line endocrine treatment of advanced breast cancer in postmenopausal patients, who failed during adjuvant or first line treatment with tamoxifen. Of the steroidal aromatase inhibitors, the orally active drug exemestane is still in phase III clinical study; the registration is expected in 1999.
抑制芳香化酶（雌激素生成中的限速酶）是绝经后晚期乳腺癌有效的内分泌治疗方法。最近，已研发出几种新型芳香化酶抑制剂，与原型芳香化酶抑制剂氨鲁米特相比，疗效有所提高且毒性降低。芳香化酶抑制剂可分为两类。第一类是非甾体类抑制剂，其作用机制与氨鲁米特相似。第二类是甾体类抑制剂，作为芳香化酶的假底物发挥作用。在非甾体类芳香化酶抑制剂中，阿那曲唑和来曲唑这两种药物最近已获批用于他莫昔芬治疗失败后的绝经后晚期乳腺癌二线内分泌治疗。这些药物的III期研究表明，与目前用氨鲁米特或醋酸甲地孕酮进行的二线治疗相比，疗效至少相当。然而，它们的毒性特征要好得多。这使得它们成为绝经后患者辅助治疗或一线他莫昔芬治疗失败后的晚期乳腺癌二线内分泌治疗的首选药物。在甾体类芳香化酶抑制剂中，口服活性药物依西美坦仍处于III期临床研究阶段；预计1999年获批。
