Pharmacokinetics, pharmacological and anti-tumour effects of the specific anti-oestrogen ICI 182780 in women with advanced breast cancer.
Pharmacokinetics, pharmacological and anti-tumour effects of the specific anti-oestrogen ICI 182780 in women with advanced breast cancer.
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DOI：
10.1038/bjc.1996.357
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发表时间：
1996-07
影响因子：
8.8
通讯作者：
Walton, P
中科院分区：
文献类型：
--
作者：
Howell, A;DeFriend, DJ;Robertson, JFR;Blamey, RW;Anderson, L;Anderson, E;Sutcliffe, FA;Walton, P
我们评估了19名对他莫昔芬耐药的晚期乳腺癌患者服用特异性类固醇抗雌激素药物ICI182780的药代动力学、药理和抗肿瘤效果。这种药物是每月一次的仓库肌肉注射。ICI 182780峰值水平在给药后8-9天的中位数出现，然后下降，但在第28天高于预计的治疗阈值。第1个月的cmax为10.5 ng/ml-1，第6个月为12.6 ng/ml-1。服药后第1个月和第6个月的AUC分别为140.5和206.8 ng·d-1，提示有一定的药物蓄积。停用他莫昔芬后，黄体生成素和卵泡刺激素水平升高，然后趋于平稳，提示ICI 182780对垂体-下丘脑轴没有影响。血清催乳素、性激素结合球蛋白(SHBG)和血脂水平无明显变化。副作用较少。未出现潮热和出汗现象，治疗对子宫内膜或阴道无明显影响。在服用他莫昔芬后，13名患者(69%)对ICI 182780有反应(7名患者有部分反应，6名患者“无变化”)，持续时间中位数为25个月。因此，ICI 182780是一种有效的二线抗雌激素药物，对肝脏、大脑或生殖道没有明显的负面影响，值得对晚期乳腺癌患者进行进一步评估。
We have assessed the pharmacokinetics, pharmacological and anti-tumour effects of the specific steroidal anti-oestrogen ICI 182780 in 19 patients with advanced breast cancer resistant to tamoxifen. The agent was administered as a monthly depot intramuscular injection. Peak levels of ICI 182780 occurred a median of 8-9 days after dosing and then declined but were above the projected therapeutic threshold at day 28. Cmax during the first month was 10.5 ng/ml-1 and during the sixth month was 12.6 ng ml-1. The AUCs were 140.5 and 206.8 ng day ml-1 on the first and sixth month of dosing respectively, suggesting some drug accumulation. Luteinising hormone (LH) and follicle-stimulating hormone (FSH) levels rose after withdrawal of tamoxifen and then plateaued, suggesting no effect of ICI 182780 on the pituitary-hypothalamic axis. There were no significant changes in serum levels of prolactin, sex hormone-binding globulin (SHBG) or lipids. Side-effects were infrequent. Hot-flushes and sweats were not induced and there was no apparent effect of treatment upon the endometrium or vagina. Thirteen (69%) patients responded (seven had partial responses and six showed "no change' responses) to ICI 182780, after progression on tamoxifen, for a median duration of 25 months. Thus ICI 182780, given by monthly depot injection, and at the drug levels described, is an active second-line anti-oestrogen without apparent negative effects on the liver, brain or genital tract and warrants further evaluation in patients with advanced breast cancer.
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影响因子：
6.4
作者：
COOPMAN, P;GARCIA, M;ROCHEFORT, H
通讯作者：
ROCHEFORT, H
DOI：
10.1093/jnci/83.20.1477
发表时间：
1991-10-16
期刊：
JOURNAL OF THE NATIONAL CANCER INSTITUTE
影响因子：
--
作者：
OSBORNE, CK;CORONADO, E;DEGREGORIO, M
通讯作者：
DEGREGORIO, M
DOI：
10.1073/pnas.89.10.4658
发表时间：
1992-05-15
影响因子：
11.1
作者：
IGNARTROWBRIDGE, DM;NELSON, KG;KORACH, KS
通讯作者：
KORACH, KS
影响因子：
3.9
作者：
NICHOLSON, RI;FRANCIS, AB;GEE, JMW
通讯作者：
GEE, JMW
影响因子：
8.8
作者：
Clarke RB;Laidlaw IJ;Jones LJ;Howell A;Anderson E
通讯作者：
Anderson E