A phase II study of sequential neoadjuvant gemcitabine plus doxorubicin followed by gemcitabine plus cisplatin in patients with operable breast cancer: prediction of response using molecular profiling.
A phase II study of sequential neoadjuvant gemcitabine plus doxorubicin followed by gemcitabine plus cisplatin in patients with operable breast cancer: prediction of response using molecular profiling.
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DOI：
10.1038/sj.bjc.6604322
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发表时间：
2008-04-22
影响因子：
8.8
通讯作者：
Perou, C. M.
中科院分区：
文献类型：
--
作者：
Julka, P. K.;Chacko, R. T.;Nag, S.;Parshad, R.;Nair, A.;Oh, D. S.;Hu, Z.;Koppiker, C. B.;Nair, S.;Dawar, R.;Dhindsa, N.;Miller, I. D.;Ma, D.;Lin, B.;Awasthy, B.;Perou, C. M.
本研究检查了基于吉西他滨的序贯联合治疗乳腺癌的病理学完全缓解（pCR）率和安全性。我们还检查了肿瘤活检的基因表达谱，以确定预测反应的生物标志物。患有大或局部晚期乳腺癌的印度女性接受4个周期的吉西他滨1200 mg m−2+阿霉素60 mg m−2（Gem+Dox），然后接受4个周期的吉西他滨1000 mg m−2+顺铂70 mg m−2（Gem+Cis）和手术。在周期1期间使用三种交替给药序列，以检查分子特征的动态变化。在接受治疗的65名女性中，13名（53名手术患者中的24.5%）获得pCR，22名（33.8%）获得完全临床缓解。第1周期第1、8天给予Gem和第2天给予Dox的患者（65例中的20例）报告了更多的毒性，G3/4血小板减少性感染/发热性中性粒细胞减少症（20例中的7例）是最常见的第1周期事件。发生了四起与毒品有关的死亡。在65例患者中的46例中，10倍交叉验证的监督分析鉴定了预测（1）8个周期后的临床完全缓解，（2）总体临床完全缓解和（3）pCR的基因表达模式，准确率为73%。该方案显示出强烈的活性。接受Gem d1、8和Dox d2的患者出现不可接受的毒性，而接受其他序列的患者具有可管理的安全性特征。基因表达模式可预测含吉西他滨新辅助治疗的获益。
This study examined the pathological complete response (pCR) rate and safety of sequential gemcitabine-based combinations in breast cancer. We also examined gene expression profiles from tumour biopsies to identify biomarkers predictive of response. Indian women with large or locally advanced breast cancer received 4 cycles of gemcitabine 1200 mg m−2 plus doxorubicin 60 mg m−2 (Gem+Dox), then 4 cycles of gemcitabine 1000 mg m−2 plus cisplatin 70 mg m−2 (Gem+Cis), and surgery. Three alternate dosing sequences were used during cycle 1 to examine dynamic changes in molecular profiles. Of 65 women treated, 13 (24.5% of 53 patients with surgery) had a pCR and 22 (33.8%) had a complete clinical response. Patients administered Gem d1, 8 and Dox d2 in cycle 1 (20 of 65) reported more toxicities, with G3/4 neutropenic infection/febrile neutropenia (7 of 20) as the most common cycle-1 event. Four drug-related deaths occurred. In 46 of 65 patients, 10-fold cross validated supervised analyses identified gene expression patterns that predicted with ⩾73% accuracy (1) clinical complete response after eight cycles, (2) overall clinical complete response, and (3) pCR. This regimen shows strong activity. Patients receiving Gem d1, 8 and Dox d2 experienced unacceptable toxicity, whereas patients on other sequences had manageable safety profiles. Gene expression patterns may predict benefit from gemcitabine-containing neoadjuvant therapy.
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DOI：
10.1097/00000421-199804000-00003
发表时间：
1998-04-01
影响因子：
2.6
作者：
Ferriere, JP;Assier, I;Chollet, P
通讯作者：
Chollet, P
影响因子：
11.2
作者：
Bertucci, F;Finetti, P;Viens, P
通讯作者：
Viens, P
影响因子：
50.5
作者：
Cleator, SJ;Makris, A;Powles, TJ
通讯作者：
Powles, TJ
影响因子：
45.3
作者：
Hannemann, J;Oosterkamp, HM;van de Vijver, MJ
通讯作者：
van de Vijver, MJ
影响因子：
11.5
作者：
Carey, Lisa A.;Dees, E. Claire;Perou, Charles M.
通讯作者：
Perou, Charles M.