使用芳香化酶抑制剂治疗策略曲唑和他莫昔芬乳腺癌模型。

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长BJ, Jelovac D, Handratta V, Thiantanawat,麦克弗森N, Ragaz J, Goloubeva噩,布罗迪

使用芳香化酶抑制剂治疗策略曲唑和他莫昔芬乳腺癌模型。

中华肿瘤杂志。2004年3月17日,96 (6):456 - 65。

PubMed ID

15026471 (在PubMed

]

文摘

背景:抗雌激素三苯氧胺对雌激素受体阳性乳腺癌有效的活动,但两个非甾体类芳香化酶抑制剂,曲唑和阿那曲唑,显示相当大的优势他莫昔芬对患者生存和耐受性。确定最优的方式使用曲唑和三苯氧胺,我们研究了其对乳腺肿瘤异种移植模型的影响,MCF-7Ca,响应抗雌激素和芳香化酶抑制剂。方法:女性切除卵巢的BALB / c裸小鼠移植瘤模型无胸腺的带异种移植肿瘤治疗每日皮下注射的一线治疗后不同时间的:没有药物(控制),它莫西芬(100 microg /天),曲唑(10 microg /天),这两种药物同时或交替四周课程每个药物(从它莫西芬的或开始的曲唑)。肿瘤体积和重量是使用线性mixed-effects模型的估计。肿瘤一倍计算,权重和肿瘤治疗组比较,调整为多个比较是用图基或Dunnett的过程。二线治疗(与他莫昔芬、曲唑或fulvestrant)时启动肿瘤的一线治疗下翻了一番。统计测试都是双面的。结果:肿瘤体积的一倍时间如下:控制,3 - 4周;它莫西芬,16周;三苯氧胺与曲唑交替,17 - 18周; tamoxifen plus letrozole, 18 weeks; letrozole alternating with tamoxifen, 22 weeks; letrozole alone, 34 weeks. First-line treatment with letrozole was superior to treatment with tamoxifen alone or with the two drugs combined (at week 16, both P<.001). Alternating tamoxifen and letrozole and alternating letrozole and tamoxifen were also not as effective as letrozole alone (at week 16, P =.002 and P<.001, respectively). Tumors progressing on tamoxifen remained sensitive to second-line therapy with letrozole compared with those remaining on tamoxifen at the end of treatment (week 28, P<.001), whereas tumors progressing on letrozole were unaffected by second-line treatment with the antiestrogens tamoxifen or fulvestrant. CONCLUSIONS: First-line letrozole therapy extends time for tumor progression in this model relative to the other treatment regimens tested. However, further studies are needed to determine the most effective second-line therapy for tumors that progress on letrozole.

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药物靶点

药物	目标	类	生物	药理作用	行动
曲唑	细胞色素P450 19 a1	蛋白质	人类	是的	拮抗剂	细节