关于后继续用药的问题

可以说说间隔4002联特的理由嘛？上来就联合？我家是易耐药，2992 6天 因为担心效果，直接上9291，现效果良好，已经21天，现在也计划下一步用药问题？求助！

       我父亲今天刚拿到复查结果，报告提示变大，我的心一下子沉到了井底，哇凉哇凉的，找大夫重新看了下片子说基本一样，心里又觉得踏实了许多，9291从3月到现在7个月了中间间隔4002，2个月，大夫让做射波刀试试，心里没注意了

前期4002用了多久？

whitesnow777 发表于 2014-10-11 21:57
前期4002用了多久？

断断续续7个月

真的不错，我家4002八个多月，现在9291三个月，本来很担心服用时间的问题，看了你家贴子感觉真是正能量，9291也7个月了，一起加油！

谢谢楼主的建议

谢谢分享！

请教下：9291后还能不能回易特单药用药啊？

效果真好，继续加油

本帖最后由 mindfury 于 2014-3-23 15:12 编辑


AZD9291耐药的癌细胞对elumetinib (AZD6244，MEK抑制剂）敏感，两者联用有可能延迟肿瘤耐药的发生。

#1722   Investigating resistance to AZD9291.

Cath Eberlein,1 Laura Ratcliffe,2 Lucy O'Brien,2 Katie Al-Khadimi,1 Henry Brown,1 Paul Fisher,1 Daniel Stetson,3 Zhongwu Lai,3 Gayle Marshall,1 Claire Barnes,1 Kenneth Thress,3 Brian Dougherty,3 William Pao,4 Darren Cross1. 1AstraZeneca, Cheshire, United Kingdom; 2Former employee of Astrazeneca, Cheshire, United Kingdom; 3AstraZeneca, Waltham, Boston, MA; 4Vanderbilt University, Nasville, TN.

First- and second-generation EGFR TKIs are established first line therapy for patients with NSCLC with activating mutations in EGFR. Unfortunately, patients ultimately develop disease progression with acquisition of a second-site EGFR T790M mutation in more than half of cases. This has led to the development of third generation EGFR TKIs which inhibit both the EGFRm+ and T790M mutations in preclinical models and are showing activity in TKI-resistant patients in Phase I studies. Despite the potential improvements brought by third generation EGFR-TKIs, advanced EGFRm+ tumor cells will still remain highly adaptable and the inevitability of further resistance will limit the effectiveness of these drugs. As such, the identification of resistance mechanisms to these agents is essential to guide future therapeutic strategies and identify novel:novel combinations.

To interrogate resistance to AZD9291, we have generated panels of EGFRm+ cell lines resistant to gefitinib (first generation TKI) and EGFRm+ and EGFRm+/T790M cell lines resistant to afatinib and AZD9291 (second and third generation TKIs, respectively). Subsequently, we characterised the cell lines using a variety of molecular profiling techniques including Next Generation Sequencing (NGS), Affymetrix gene expression analysis, and phenotypic profiling following pharmacological modulation by small molecule inhibitors of canonical signaling pathways.

The effects on cell survival across the range of resistant models by a panel of pathway inhibitors indicated that resistance to the EGFR inhibitors, in particular AZD9291, is frequently associated with increased sensitivity to selumetinib (AZD6244; ARRY-142886) (MEK1/2 inhibitor), suggesting that ERK signaling is commonly reactivated to circumvent inhibition of the EGFR pathway. Molecular characterisation of the panel of cell lines suggests a range of different resistance mechanisms may be responsible for reactivation of ERK signaling, including a decrease in negative regulators of ERK such as DUSP6 or an epithelial to mesenchymal transition consistent with previous observations.

Collectively, these data suggest that combining an EGFR TKI with a MEK inhibitor could prevent or delay resistance and drive superior duration of benefit from these agents.