Influence of letrozole and anastrozole on total body aromatization and plasma estrogen levels in postmenopausal breast cancer patients evaluated in a randomized, cross-over study
Influence of letrozole and anastrozole on total body aromatization and plasma estrogen levels in postmenopausal breast cancer patients evaluated in a randomized, cross-over study
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DOI：
10.1200/jco.2002.20.3.751
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发表时间：
2002-02-01
影响因子：
45.3
通讯作者：
Lonning, PE
中科院分区：
文献类型：
--
作者：
Geisler, J;Haynes, B;Lonning, PE
目的：比较阿那曲唑和来曲唑对雌激素受体阳性的转移性乳腺癌患者全身芳香化和血浆雌激素水平的影响。方法：12例绝经后转移性乳腺癌患者随机分为阿那曲唑1 mg口服(PO)和来曲唑2.5 mg口服，每日1次，疗程6周。在治疗前和每个治疗周期结束时，使用双标记同位素技术测定全身芳构化，包括用高效液相色谱分离代谢物。用高灵敏放射免疫法测定每次注射前血浆雌酮(E-1)、雌二醇(E-2)和硫酸雌酮(E，S)水平。在阿那曲唑治疗期间，12名患者中有11名患者在治疗期间检测到芳香化酶水平(整个组的平均百分比抑制率为97.3%)，而在来曲唑治疗期间，12名患者中未检测到芳香化酶水平(所有患者的抑制率均为99.1%；Wilcoxon，P=.0022，比较两种药物方案)。阿那曲唑治疗后血浆E-1、E-2和E_1s水平分别下降81.0%、84.9%和93.5%，而来曲唑治疗后血浆E-1、E-2和E_1s水平分别下降84.3%、87.8%和98.0%。与阿那曲唑相比，来曲唑对E、E、S的抑制作用明显优于阿那曲唑(P分别为0.019和0.0037)。结论：与阿那曲唑(每日1次，每次1 mg)相比，来曲唑(每日1次，2.5 mg)对绝经后转移性乳腺癌患者的全身芳香化和血浆雌激素水平有更强的抑制作用。(C)2002年，由美国临床肿瘤学会提供。
Purpose: To compare the effects of the two novel, potent, nonsteroidal aromatase inhibitors anastrozole and letrozole on total-body aromatization and plasma estrogen levels.Patients and Methods: Twelve postmenopausal women with estrogen receptor-positive, metastatic breast cancer were treated with anastrozole 1 mg orally (PO) and letrozole 2.5 mg PO once daily, each given for a time interval of 6 weeks in a randomized sequence. Total-body aromatization was determined before treatment and at the end of each treatment period using a dual-label isotopic technique involving isolation of the metabolites with high-performance liquid chromatography. Plasma levels of estrone (E-1), estradiol (E-2), and estrone sulfate (E,S) were determined in samples obtained before each injection using highly sensitive radioimmunoassays.Results: Pretreatment aromatase levels ranged from 1.68% to 4.27%. On-treatment levels of aromatase were detectable in 11 of 12 patients during treatment with anastrozole (mean percentage inhibition in the whole group, 97.3%) but in none of the 12 patients during treatment with letrozole (> 99.1 % suppression in all patients; Wilcoxon, P = .0022, comparing the two drug regimens). Treatment with anastrozole suppressed plasma levels of E-1, E-2, and E1S by a mean of 81.0%, 84.9%, and 93.5%, respectrively, whereas treatment with letrozole caused a corresponding decrease of 84.3%, 87.8% and 98.0%, respectively. The suppression of E, and E,S was found to be significantly better during treatment with letrozole compared with anastrozole (P = .019 and .0037, respectively).Conclusion: This study revealed letrozole (2.5 mg once daily) to be a more potent suppressor of total-body aromatization and plasma estrogen levels compared with anastrozole (I mg once daily) in postmenopausal women with metastatic breast cancer. (C) 2002 by American Society of Clinical Oncology.