Effect of age and single versus multiple dose pharmacokinetics of letrozole (Femara) in breast cancer patients.

Letrozole (trademark Femara) is a new orally active, potent and selective aromatase inhibitor for the hormonal treatment of advanced breast cancer in postmenopausal women. The pharmacokinetics of letrozole and the suppression of peripheral estrogens were studied in 28 breast cancer patients after a single dose and at steady state. The pharmacokinetics of two distinct age groups (> or =50, < or =65, N=15 and > or =70 years old, N=9) were compared. There were no significant differences in area under the curve (AUC) or terminal half-life between the two age groups neither after a single dose nor at steady state. However, when comparing steady state to single dose kinetics, half-life and AUC increased significantly by 42% (90% CI: 1.13, 1.78) and 28% (90% CI: 1.12, 1.47), respectively. This deviation from linearity was probably due to a partial saturation or auto-inhibition of the dominant metabolic clearance mechanism of letrozole. At steady state, approximately 70% of the administered dose was excreted in urine as unchanged letrozole (6.0+/-3.8%) or as the glucuronide of the major, pharmacologically inactive metabolite CGP44645 (64.2+/-22.7%). A single dose of letrozole caused suppression of serum estrogen levels close to the quantification limit of the assay. No difference between single dose suppression and suppression at steady state could be detected.     

弗隆和氨鲁米特治疗绝经后妇女晚期乳腺癌临床观察

目的:观察弗隆和氨鲁米特治疗绝经后晚期乳腺癌的疗效和不良反应.方法:50例绝经后晚期乳腺癌患者随机进入弗隆组26例和氨鲁米特组24例.弗隆2.5mg口服,每天1次.氨鲁米特,第1周125mg口服,每日2次;第2周,250mg,每日2次;第3周250mg,每日3次;从第4周开始,250mg,每日4次.治疗30天为1周期.结果:弗隆组有效患者(CR PR)7例(26.9%),高于氨鲁米特组3例(12.5%),但差异无显著性(P=0.294).两组病情稳定(SD)患者分别有14例(53.8%)和12例(50.0%);病情进展(PD)患者分别有5例(19.2%)和9倒(37.5%).两药疗效在不同受体状态、无病间期、病变部位和治疗阶段的分层比较,差异均无显著性(P值均＞0.05).弗隆组主要的不良反应有乏力(15.4%)、食欲下降(11.5%),头晕、恶心、头痛、嗜睡发生率均＜8%,且程度较轻;氨鲁米特组恶心(25.0%)、呕吐(1 6 7%)发生明显高于弗隆组,差异有显著性(P值分别为0.045和0.046);头晕(25.0%)、乏力(20.8%)、食欲下降(16.7%)、嗜睡(12.5%)、皮肤瘙痒(12.5%)的发生也均高于弗隆组,但差异无显著性(P值均＞0.05),另外有1例患者出现过敏性皮疹.结论:弗隆治疗绝经后晚期乳腺癌有一定疗效,部分不良反应比氨鲁米特轻,患者耐受性强.