Lipton A, Demers L M, Harvey H A, Kambic K B, Grossberg H, Brady C, Adlercruetz H, Trunet P F, Santen R J
Department of Medicine, M. S. Hershey Medical Center, Pennsylvania State University, Hershey 17033, USA.
Cancer. 1995 Apr 15;75(8):2132-8. doi: 10.1002/1097-0142(19950415)75:8<2132::aid-cncr2820750816>3.0.co;2-u.
Letrozole (CGS 20267), a triazole derivative, is a new, once-daily, oral nonsteroidal inhibitor of aromatase activity.
In this Phase I trial, 23 heavily pretreated postmenopausal patients with metastatic breast cancer received letrozole at doses ranging from 0.1 to 5.0 mg once daily.
No hematologic, biochemical, or significant clinical toxicity was encountered. Serial steroid measurements were determined in 19 of these patients. Letrozole at all doses tested produced a marked suppression of plasma estrone, estradiol, estrone sulfate, and urine estrone and estradiol. This was observed within 24 hours of the initial dose of letrozole and resulted in a greater than 90% suppression of plasma and urinary estrogen levels within 2 weeks. Letrozole appears to be highly selective in its action and does not compromise glucocorticoid or mineralocorticoid production or thyroid function. Of the 21 evaluable patients, there were 2 with partial responses and 7 with stable disease.
Letrozole is a well tolerated, potent, and specific inhibitor of estrogen biosynthesis in postmenopausal patients with metastatic breast cancer.
来曲唑（CGS 20267），一种三唑衍生物，是一种新型的、每日一次的口服非甾体芳香化酶活性抑制剂。
在这项I期试验中，23例经过大量预处理的绝经后转移性乳腺癌患者接受了剂量范围为0.1至5.0毫克的来曲唑，每日一次。
未出现血液学、生化或明显的临床毒性。对其中19例患者进行了系列类固醇测量。所有测试剂量的来曲唑均显著抑制了血浆雌酮、雌二醇、硫酸雌酮以及尿液中的雌酮和雌二醇。在来曲唑初始剂量后的24小时内即可观察到这种抑制作用，并且在2周内导致血浆和尿液雌激素水平抑制超过90%。来曲唑的作用似乎具有高度选择性，不会损害糖皮质激素或盐皮质激素的产生或甲状腺功能。在21例可评估患者中，有2例部分缓解，7例病情稳定。
来曲唑对于绝经后转移性乳腺癌患者是一种耐受性良好、强效且特异性的雌激素生物合成抑制剂。
