A phase II study of 17-allylamino-17-demethoxygeldanamycin in metastatic or locally advanced, unresectable breast cancer.
A phase II study of 17-allylamino-17-demethoxygeldanamycin in metastatic or locally advanced, unresectable breast cancer.
复制标题
DOI：
10.1007/s10549-011-1866-7
复制
发表时间：
2012-02
影响因子：
3.8
通讯作者：
LoRusso, Patricia M.
中科院分区：
文献类型：
--
作者：
Gartner, Elaina M.;Silverman, Paula;Simon, Michael;Flaherty, Lawrence;Abrams, Judith;Ivy, Percy;LoRusso, Patricia M.
热休克蛋白90（Hsp 90）是乳腺癌治疗的一个有吸引力的靶点，因为它是已知参与乳腺癌生长和发展的几种蛋白质的正确折叠和稳定所必需的。这些蛋白质包括表皮生长因子受体、人表皮生长因子受体2（HER 2）、雌激素受体（ER）、孕酮受体（PR）和src。17-烯丙基氨基-17-去甲氧基格尔德霉素（17-AAG）是一种正在开发用于乳腺癌治疗的静脉内Hsp 90抑制剂。我们在转移性和局部晚期乳腺癌患者中进行了一项17-AAG 220 mg/m2的II期研究，每21天给药1、4、8和11天。由于我们预期Hsp 90抑制的分子效应不仅限于ER、PR和HER 2下调，还影响各种其他细胞蛋白，因此未根据ER、PR或HER 2状态选择患者。11例患者，包括6例三阴性乳腺癌患者，入组并接受治疗。无缓解，3例患者的最佳缓解为疾病稳定。5例患者发生了3/4级毒性，主要是肝脏和肺部毒性。基于这些结果，我们不建议进一步研究17-AAG在这个剂量方案或在乳腺癌患者中。
Heat shock protein 90 (Hsp90) is an attractive target for breast cancer treatment, as it is required for the proper folding and stabilization of several proteins known to be involved in breast cancer growth and development. These proteins include the epidermal growth factor receptor, human epidermal growth factor receptor 2 (HER2), estrogen receptor (ER), progesterone receptor (PR), and src. 17-Allylamino-17-demethoxygeldanamycin (17-AAG) is an intravenous Hsp90 inhibitor in development for breast cancer treatment. We conducted a phase II study of 17-AAG 220 mg/m2 on days 1, 4, 8, and 11 every 21 days in patients with metastatic and locally advanced breast cancer. Since we expected the molecular effects of Hsp90 inhibition to extend beyond just ER, PR, and HER2 down regulation and to impact a variety of other cellular proteins, patients were not selected based on ER, PR, or HER2 status. Eleven patients, including 6 patients with triple negative breast cancer, were enrolled and treated. There were no responses and 3 patients had stable disease as their best response. Five patients developed grade 3/4 toxicities, which were primarily hepatic and pulmonary. Based on these results, we do not recommend further study of 17-AAG at this dosing schedule or in unselected breast cancer patients.
登录
查看更多内容
DOI：
10.1073/pnas.96.5.1858
发表时间：
1999-03-02
影响因子：
11.1
作者：
Nawaz, Z;Lonard, DM;O'Malley, BW
通讯作者：
O'Malley, BW
影响因子：
45.3
作者：
Grem, JL;Morrison, G;Wilson, RH
通讯作者：
Wilson, RH
影响因子：
11.5
作者：
Nowakowski, Grzegorz S.;McCollum, Andrea K.;Erlichman, Charles
通讯作者：
Erlichman, Charles
影响因子：
9.7
作者：
Yano, M;Naito, Z;Asano, G
通讯作者：
Asano, G
影响因子：
11.5
作者：
Ramanathan, RK;Trump, DL;Egorin, MJ
通讯作者：
Egorin, MJ