CT引导下氩氦刀联合阿法替尼对肺腺癌患者的临床疗效研究

目的 探究CT引导下氩氦刀联合化疗或阿法替尼对肺腺癌患者近期疗效与远期生存和复发情况的影响。方法 选择2015年1月至2016年9月于固安县人民医院接受一线治疗的晚期肺腺癌患者100例,随机数字法分为对照组（50例）和阿法替尼组（50例）,在应用CT引导下氩氦刀冷冻治疗的基础上,对照组采用吉西他滨联合顺铂的化疗方案,阿法替尼组采用口服阿法替尼治疗。比较两组患者的近期疗效、总生存期、无进展生存期,局部复发与远处转移情况以及并发症和不良反应发生率。结果 阿法替尼组的客观缓解率、无进展生存期和远处转移时间明显高于对照组（均P＜005）;两组的局部复发时间和并发症发生率差异无统计学意义（P=0070; P=0758）;阿法替尼组的不良反应发生率明显低于对照组（P＜005）。结论 CT引导下氩氦刀联合阿法替尼治疗晚期肺腺癌具有较高的疗效和较好的远期生存情况。     

Anti-tumour activity of afatinib, an irreversible ErbB family blocker, in human pancreatic tumour cells

Background:

The combination of the reversible epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) erlotinib with gemcitabine obtained FDA approval for treating patients with pancreatic cancer. However, duration of response is often limited and there is currently no reliable predictive marker.

Methods:

We determined the sensitivity of a panel of human pancreatic tumour cell lines to treatment with afatinib, erlotinib, monoclonal antibody (mAb) ICR62, and gemcitabine, using the Sulforhodamine B colorimetric assay. The effect of these agents on cell signalling and cell-cycle distribution was determined by western blot and flow cytometry, respectively.

Results:

At 200 n, ICR62 had no effect on growth of these tumour cells with the exception of BxPC-3 cells. BxPC-3 cells were also sensitive to treatment with afatinib and erlotinib with respective IC₅₀ values of 11 and 1200 n. Compared with erlotinib, afatinib was also more effective in inhibiting the growth of the other human pancreatic tumour cell lines and in blocking the EGF-induced phosphorylation of tyrosine, EGFR, MAPK, and AKT. When tested in BxPC-3 xenografts, afatinib induced significant delay in tumour growth.

Conclusion:

The superiority of afatinib in this study encourages further investigation on the therapeutic potential of afatinib as a single agent or in combination with gemcitabine in pancreatic cancer.     

Beyond trastuzumab: novel therapeutic strategies in HER2-positive metastatic breast cancer

The use of trastuzumab, a monoclonal antibody that targets the human epidermal growth factor receptor 2 (HER2) alteration present in 25 to 30% of breast cancers, has been associated with improved survival outcomes in both the adjuvant and metastatic settings. However, despite the robust clinical efficacy of trastuzumab in HER2-positive metastatic breast cancer (MBC), primary and secondary resistance remains a clinical challenge. Although lapatinib has demonstrated modest activity in this setting, trials reported to date have yet to demonstrate improvements in overall survival with its use. Novel therapeutic strategies to circumvent trastuzumab resistance are warranted, and agents targeting the HER, vascular endothelial growth factor, heat shock protein 90, phosphoinositide 3 kinase/Akt/mammalian target of rapamycin, and insulin-like growth factor-1 receptor pathways represent rational approaches in the management of HER2-positive disease. In this review, early-phase and emerging trial data surrounding the use of these promising agents in HER2-positive MBC will be discussed.     

阿法替尼引起痤疮样药疹二例

阿法替尼属于表皮生长因子受体抑制剂,现广泛应用于非小细胞肺癌的治疗,该药物的主要毒性反应之一为皮肤不良反应,最常见为痤疮样药疹,本文报道2例服用阿法替尼后出现痤疮样药疹的患者。     

Afatinib treatment for her-2 amplified metastatic colorectal cancer based on patient-derived xenograft models and next generation sequencing

Background: Substantial progress has been made in metastatic colorectal cancer (mCRC) treatment, but there is still a fraction of patients cannot find any effective therapeutic strategy after guideline-recommended standard chemotherapy and molecular targeted therapy.

Case presentation: Here we present a KRAS/NRAS/BRAF wild-type mCRC patient who has been previously treated with FOLFIRI (fluorouracil, leucovorin, and irinotecan), XELOX (capecitabine and oxaliplatin), cetuximab and bevacizumab, and then received the next generation sequencing (NGS) and whose metastatic subcutaneous nodule was resected to generate patient-derived xenograft (PDX) models. The NGS revealed HER-2 amplification as well as an activating mutation S310F and PDX models tested several drugs finding that afatinib was the optimal agent with notable efficacy and well tolerance among 6 regimens. Therefore, this patient started to take afatinib orally and achieved 3 months progression-free survival (PFS) and relief of clinical symptoms without severe adverse effects.

Conclusions: NGS and PDX models have great significance for precision and individualized medicine in the mCRC treatment, especially for patients whose diseases have been progressed after multiline standard therapies.