Harvey H A
Section of Hematology-Oncology, Hershey Medical Center, Penn State Geissinger Health Systems, Hershey, Pennsylvania, USA.
Oncology (Williston Park). 1998 Mar;12(3 Suppl 5):32-5.
The new generation of potent steroidal and nonsteroidal inhibitors of the enzyme aromatase act by decreasing estrogen production throughout the body in postmenopausal women. The most potent of these agents may also inhibit estrogen synthesis within metastatic breast cancer tissue. The newly developed, orally administered, nonsteroidal competitive inhibitors, such as anastrozole (Arimidex), letrozole (Femara), and vorozole (Rizivor), are a thousand times more potent inhibitors of aromatase than is aminoglutethimide. Furthermore, these agents are highly selective. In several large randomized trials, the new inhibitors produced similar response rates as megestrol acetate (160 mg/d) in postmenopausal women with hormone-dependent breast cancer, but showed a trend toward improved response duration and survival. They also produced less weight gain and fewer cardiovascular and thromboembolic side effects. In addition, letrozole proved superior to aminoglutethimide in another randomized trial. Both anastrozole (1.0 mg/d) and letrozole (2.5 mg/d) have now been approved as second-line treatment for hormone-dependent breast cancer in postmenopausal women in whom disease has progressed following tamoxifen treatment. Either drug should replace the routine use of megestrol acetate in this setting. Ongoing clinical studies are comparing anastrozole and letrozole to antiestrogens as first-line endocrine therapy for metastatic breast cancer. Other trials will study the possible roles of these compounds as adjuvant therapy and chemoprevention for breast cancer.
新一代强效甾体和非甾体芳香化酶抑制剂通过降低绝经后女性体内雌激素的生成来发挥作用。其中最有效的药物还可能抑制转移性乳腺癌组织内的雌激素合成。新开发的口服非甾体竞争性抑制剂，如阿那曲唑（瑞宁得）、来曲唑（弗隆）和伏罗唑（瑞婷），对芳香化酶的抑制作用比氨鲁米特强一千倍。此外，这些药物具有高度选择性。在几项大型随机试验中，对于患有激素依赖性乳腺癌的绝经后女性，这些新型抑制剂产生的反应率与醋酸甲地孕酮（160毫克/天）相似，但在反应持续时间和生存率方面有改善的趋势。它们还导致体重增加较少，心血管和血栓栓塞副作用也较少。此外，在另一项随机试验中，来曲唑被证明优于氨鲁米特。阿那曲唑（1.0毫克/天）和来曲唑（2.5毫克/天）现已被批准作为他莫昔芬治疗后疾病进展的绝经后激素依赖性乳腺癌女性的二线治疗药物。在这种情况下，这两种药物都应取代醋酸甲地孕酮的常规使用。正在进行的临床研究正在比较阿那曲唑和来曲唑与抗雌激素药物作为转移性乳腺癌一线内分泌治疗的效果。其他试验将研究这些化合物作为乳腺癌辅助治疗和化学预防的可能作用。
