艾迪注射液联合GP方案治疗EGFR-TKI获得性耐药的晚期非小细胞肺癌疗效观察

目的：观察艾迪注射液联合GP化疗方案治疗表皮生长因子酪氨酸激酶抑制剂（EGFR-TKI）治疗失败后的晚期非小细胞肺癌（NSCLC）的临床疗效。方法选取2011年12月—2013年12月襄阳市中心医院接受EGFR-TKI治疗后出现获得性耐药的62例晚期NSCLC患者,分为对照组和治疗组,每组各31例。对照组给予GP方案常规化疗：注射用盐酸吉西他滨1000 mg/m2,1次/d,持续静脉滴注3 h,第1、8天给药;顺铂注射液75 mg/m2,1次/d,静脉滴注,第1天给药。21天为1个周期,连续观察2个周期。治疗组在对照组的基础上静脉滴注艾迪注射液,50 mL溶于5%葡萄糖溶液500 mL静滴,1次/d,2周为1个疗程,连续使用3个疗程。评价两组患者的近期疗效指标客观有效率（ORR）、疾病控制率（DCR）以及远期疗效指标无进展生存期（PFS）、总生存期（OS）。患者的生活质量（KPS）以 Karnofsky 评分进行评定。对毒副反应进行评价。结果62例患者均可评价疗效,其中治疗组ORR 61.29%,DCR 83.87%,对照组ORR 35.48%,DCR 70.97%,治疗组的ORR、DCR均明显高于对照组,两组比较差异具有统计学意义（P＜0.05、0.01）。治疗组中位PFS为6.3（1.2～20.6）个月,对照组中位PFS为3.4（0.7～10.3）个月,两组比较差异具有统计学意义（P＜0.05）。治疗组死亡患者的中位OS为15.1（1.4～28.2）,对照组死亡患者的中位OS为8.9（1.0～17.2）个月,两组患者中位OS差异无统计学意义。治疗后,治疗组患者的KPS评分显著高于对照组,两组比较差异具有统计学意义（P＜0.01）。治疗组不良反应发生率为32.3%,对照组不良反应发生率为37.8%,两组不良反应发生率比较无显著性差异。治疗组胃肠道反应发生率为38.7%（12/31）,对照组胃肠道反应发生率为51.6%（16/31）,与对照组比较显著减少（P＜0.01）。结论艾迪注射液联合 GP 化疗方案治疗EGFR-TKI获得性耐药的晚期NSCLC的疗效较好,能延缓疾病进展,延长生存期,提高生存质量,且减轻化疗带来的胃肠道反应,值得临床进一步研究。     

EGFR- TKIs类药物治疗晚期非小细胞肺癌的药物经济学评价

【摘要】目的：引入Markov模型评价埃克替尼、吉非替尼和厄洛替尼三种EGFR- TKIs类药物二线治疗晚期非小细胞肺癌(NSCLC)的经济性,指导临床合理用药。方法：建立埃克替尼、吉非替尼和厄洛替尼治疗晚期非小细胞肺癌的Markov模型,分别对三种药物治疗晚期非小细胞肺癌患者疾病稳定、疾病缓解、疾病进展和死亡的动态变化进行模拟,同时对成本和效用值进行敏感度分析,找出临床相对较优的治疗药物。结果：Markov模型成本-效用分析显示：3%的贴现率下埃克替尼治疗晚期非小细胞肺癌3年所需累积成本为375594.37元,累积效用为1.50个质量调整生命年;吉非替尼所需累积成本为531222.33元,累积效用为1.51个质量调整生命年;厄洛替尼所需累积成本为694611.22元,累积效用为1.51个质量调整生命年。敏感度分析显示各参数在设定的范围内变化不影响模型分析结论。结论：三种EGFR- TKIs类药物相比,埃克替尼的成本效用比(250396.25元/QALY)远远小于吉非替尼(351802.87元/QALY)和厄洛替尼(460007.43元/QALY),是优选方案。因此,应优先选择埃克替尼作为晚期非小细胞肺癌的治疗药物,从而获得更优的经济学效益,使有限的医疗资源利用最大化。     

Lack of relationship between EGFR-1 immunohistochemical expression and prognosis in a multicentre clinical trial of 93 patients with advanced primary ovarian epithelial cancer (GINECO group)

Epidermal growth factor receptor 1 (EGFR-1) overexpression is usually described as linked with a worse prognosis in a variety of tumours of epithelial origin. However, its role in ovarian cancer is still controversial. The aim of the present study was to analyse the prognostic impact of EGFR-1 in a retrospective series of 93 stage III-IV primary ovarian epithelial tumours. All patients, enrolled in a multicentre GINECO prospective clinical trial, were treated with the same platinum-based combination chemotherapy, and were followed up with a median of 69 months. Epidermal growth factor receptor 1 plasma membrane expression, assessed by immunohistochemistry on paraffin-embedded tissues, was correlated with clinical parameters as well as immunohistochemical expression results of HER-2 (c-erbB-2), BAX, BCL-2, p53 and anti-Ki-67, previously studied in the same series of patients. Positive immunostaining for EGFR-1 was seen in 31 of the 93 analysed cases (33%). No correlation was found between EGFR-1 expression and clinical parameters. No correlation was found between EGFR-1 expression and other biological markers, except for HER-2, which was limit for significance. Indeed, among the EGFR-1-negative cases, 10.3% expressed HER-2, whereas the HER-2-expressing tumours accounted for 27.6% of EGFR-1-positive cases (P=0.06). Epidermal growth factor receptor 1 overexpression had no prognostic impact on both overall and progression-free survival through univariate and multivariate analyses. The potential effect of EGFR-1 and HER-2 co-expression on targeted therapy against EGFR-1 and/or HER-2 molecules has to be further analysed.     

Aquaporin 8 Involvement in Human Cervical Cancer SiHa Migration via the EGFR-Erk1/2 Pathway

Overexpression of aquaporins (AQPs) has been reported in several human cancers. Epidermal growth factor receptor (EGFR)-extracellular signal-regulated kinases 1/2 (Erk1/2) are associated with tumorigenesis and cancer progression and may upregulate AQP expression. In this study, we demonstrated that EGF (epidermal growth factor) induces SiHa cells migration and AQP8 expression. Wound healing results showed that cell migration was increased by 2.79-1.50-fold at 24h and 48h after EGF treatment. AQP8 expression was significantly increased(3.33-fold) at 48h after EGF treatment in SiHa cells. An EGFR kinase inhibitor, PD153035, blocked EGFinduced AQP8 expression and cell migration and AQP8 expression was decreased from 1.59-fold (EGF-treated) to 0.43-fold (PD153035-treated) in SiHa. Furthermore, the MEK (MAPK (mitogen-activated protein kinase)/ Erk (extracellular signal regulated kinase)/Erk inhibitor U0126 also inhibited EGF-induced AQP8 expression and cell migration. AQP8 expression was decreased from 1.21-fold (EGF-treated) to 0.43-fold (U0126-treated).Immunofluorescence microscopy further confirmed the results. Collectively, our findings show that EGF induces AQP8 expression and cell migration in human cervical cancer SiHa cells via the EGFR/Erk1/2 signal transduction pathway.     

Outcome prediction values of soluble human epidermal growth factor receptor-2 extracellular domain in metastatic breast cancer

Background: HER-2 overexpression is an independent predictor for poor prognosis of breast cancer patients. Recently, extracellular domain of HER-2 (ECD) was found detectable in the serum of breast cancer patients. In this prospective study, we wonder whether ECD levels predict the clinical outcome of metastatic breast cancer patients. Methods: ECD were measured in 190 women with metastatic breast cancer. Chi-square test was performed to determine the relationship between ECD status and clinical outcomes. Kaplan-Meier curves were applied for survival analysis. Results: Elevated ECD levels were significantly associated with short-term response to Herceptin treatment. The median PFS was significantly longer in ECD-Low patients. The patients who remained low ECD levels or achieved low ECD levels after treatments have significantly longer PFS than those whose levels remained high or converted from low to high. Conclusions: Overall, our results support the clinical utility of measuring serum HER2 ECD levels in patients with advanced breast cancer. Baseline and serial measurements of serum ECD levels are reliably predictive of clinical outcome of breast cancer patients.     

The potential for targeting HER2 therapeutically in esophageal cancer – a grasp at straws?

Introduction: Human EGFR-2 (HER2) has an impact on cellular proliferation and survival. HER2 overexpression has been shown to be a marker for poorer prognosis in several malignancies. Trastuzumab, a humanized mAb, is successfully used to target HER2 in breast cancer. The effect of targeting HER2 in esophageal cancer (EC) is the focus of current trials.

Areas covered: Basic knowledge, detection techniques and definitions of HER2 overexpression, as well as the molecular mechanisms underlying the effects of trastuzumab on HER2, are reviewed. An overview of research on the prognostic and predictive relevance of HER2 in EC is given, as well as an overview of current trials targeting HER2 in EC.

Expert opinion: The first aim of novel targeted therapies must be perioperative neoadjuvant and adjuvant applications, as surgery is the only option for curative treatment in patients with stage I – III EC. Regarding targeted therapies in EC, HER2 is currently the most promising target. Trials of trimodal neoadjuvant therapy regimes (neoadjuvant radiochemotherapy plus trastuzumab) are currently recruiting. However, the prognostic impact of HER2 overexpression in EC remains ambiguous. Targeting HER2 may have negative and positive impacts on survival, depending on which subgroup of EC patients is treated.