EFFECTS OF FADROZOLE (CGS-16949A) AND LETROZOLE (CGS-20267) ON THE INHIBITION OF AROMATASE-ACTIVITY IN BREAST-CANCER PATIENTS
EFFECTS OF FADROZOLE (CGS-16949A) AND LETROZOLE (CGS-20267) ON THE INHIBITION OF AROMATASE-ACTIVITY IN BREAST-CANCER PATIENTS
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DOI：
10.1007/bf00682744
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发表时间：
1994-01-01
影响因子：
3.8
通讯作者：
DEMERS, LM
中科院分区：
文献类型：
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作者：
DEMERS, LM
盐酸法倔唑（CGS 16949A）和来曲唑（CGS 20267）是两种最新的非甾体类口服活性芳香酶抑制剂，目前正在评估作为激素依赖型转移性乳腺癌患者的二线治疗。在一项I期临床疗效研究中，我们检测了这两种咪唑衍生物在一组绝经后转移性乳腺癌患者中抑制雌激素合成的能力。这两种药物在相对较低的剂量下都是有效和快速的芳香酶活性抑制剂，这可以通过它们抑制这些患者的血和尿雌二醇和雌酮以及血硫酸雌酮水平的能力来证明。来曲唑似乎是更有效的两个，与超过95%的抑制血浆和尿雌激素治疗2周内观察到。来曲唑在抑制芳香酶活性方面似乎比法倔唑更具选择性，因为在所有测试剂量下，来曲唑治疗对皮质醇和醛固酮输出没有明显的损害，通过这些咪唑衍生物抑制芳香酶活性作为激素依赖性乳腺癌患者的二线治疗似乎是激素消融治疗的有利替代形式，对治疗这种恶性肿瘤有很大的希望。
Fadrozole Hydrochloride (CGS 16949A) and Letrozole (CGS 20267), are two of the newest non-steroidal, orally active aromatase inhibitors currently being evaluated as second line treatment of patients with hormone dependent forms of metastatic breast cancer. In a phase I clinical efficacy study, we examined the ability of these two imidazole derivatives to suppress the synthesis of estrogen in a cohort of postmenopausal patients with metastatic breast cancer. Both medications at relatively low doses were potent and rapid inhibitors of aromatase activity as evidenced by their ability to suppress the level of blood and urine estradiol and estrone as well as blood estrone sulfate in these patients. Letrozole appeared to be the more potent of the two, with over 95% suppression of both plasma and urinary estrogens observed within 2 weeks of therapy. Letrozole appeared to be more selective than Fadrozole in inhibiting aromatase activity in that no compromise in cortisol and aldosterone output was evident with Letrozole therapy at all of the doses tested, a compromise clearly seen with Fadrozole.The inhibition of aromatase activity by these imidazole derivatives as second line therapy for patients with hormone dependent breast cancer appears to be a favorable alternative form of hormone ablative therapy and holds considerable promise for the treatment of this malignancy.