在乳腺癌模型中使用芳香酶抑制剂来曲唑和他莫昔芬的治疗策略。

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Long BJ, Jelovac D, Handratta V, Thiantanawat A, MacPherson N, Ragaz J, Goloubeva OG, Brodie AM

在乳腺癌模型中使用芳香酶抑制剂来曲唑和他莫昔芬的治疗策略。

中华肿瘤学杂志2003,17(6):456-65。

PubMed ID

15026471 (PubMed视图

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摘要

背景:抗雌激素他莫昔芬对雌激素受体阳性乳腺癌有很强的活性，但两种非甾体芳香化酶抑制剂来曲唑和阿那曲唑在患者生存率和耐受性方面比他莫昔芬表现出相当大的优势。为了确定来曲唑和他莫昔芬的最佳使用方法，我们研究了它们对乳房肿瘤异种移植模型MCF-7Ca的影响，该模型对抗雌激素和芳香化酶抑制剂都有反应。方法:携带异种移植瘤的雌性BALB/c无胸腺裸鼠每天皮下接受以下一线治疗之一，持续时间不同:不使用药物(对照)，单独使用他莫西芬(100微克/天)，单独使用来曲唑(10微克/天)，同时使用这两种药物，或交替使用每种药物4周疗程(开始使用他莫西芬或开始使用来曲唑)。使用线性混合效应模型估计肿瘤体积和重量。计算肿瘤加倍的时间，比较治疗组的肿瘤重量，并与Tukey或Dunnett手术进行多次比较调整。二线治疗(他莫昔芬、来曲唑或氟维司坦)在一线治疗下肿瘤体积翻倍时开始。所有统计检验均为双侧检验。结果:肿瘤体积加倍的时间为:对照组，3-4周;单独使用他莫西芬，16周;他莫昔芬与来曲唑交替使用，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.

引用本文的药物库数据

药物靶点

药物	目标	种类	生物	药理作用	行动
曲唑	细胞色素P450 19A1	蛋白质	人类	是的	拮抗剂	细节