小狗阅读会员会员
医学顶刊SCI精读工具

扫码登录小狗阅读

阅读SCI医学文献
Document
订阅泛读方向 订阅泛读期刊
  • 我的关注
  • 我的关注
  • {{item.title}}

    按需关注领域/方向,精准获取前沿热点

  • {{item.title}}

    {{item.follow}}人关注

  • {{item.subscribe_count}}人订阅

    IF:{{item.impact_factor}}

    {{item.title}}

Safety and efficacy of first-line dacomitinib in Japanese patients with advanced non-small cell lung cancer.

Dacomitinib一线治疗日本晚期非小细胞肺癌患者的安全性和疗效。

  • 影响因子:4.60
  • DOI:10.1111/cas.14384
  • 作者列表:"Nishio M","Kato T","Niho S","Yamamoto N","Takahashi T","Nogami N","Kaneda H","Fujita Y","Wilner K","Yoshida M","Isozaki M","Wada S","Tsuji F","Nakagawa K
  • 发表时间:2020-05-01
Abstract

:In a subgroup of Japanese patients in the ARCHER 1050 randomized phase 3 trial, we evaluated the efficacy and safety and determined the effects of dose modifications on adverse events (AE) and therapy management of first-line oral dacomitinib 45 mg compared with oral gefitinib 250 mg, each once daily in 28-d cycles, in patients with EGFR-activating mutation-positive (EGFR-positive; exon 19 deletion or exon 21 L858R substitution mutations) advanced non-small cell lung cancer (NSCLC). The primary endpoint was progression-free survival (PFS; RECIST, version 1.1, by blinded independent review). In 81 Japanese patients (40 dacomitinib, 41 gefitinib), PFS was longer with dacomitinib compared with gefitinib (hazard ratio [HR], 0.544 [95% confidence interval {CI}, 0.307-0.961]; 2-sided P = .0327; median 18.2 for dacomitinib [95% CI, 11.0-31.3] mo, 9.3 [95% CI, 7.4-14.7] mo for gefitinib). The most common Grade 3 AEs were dermatitis acneiform with dacomitinib (27.5%) and increased alanine aminotransferase with gefitinib (12.2%). A higher proportion of patients receiving dacomitinib (85.0%) compared with gefitinib (24.4%) had AEs leading to dose reduction. Incidence and severity of diarrhea, dermatitis acneiform, stomatitis and paronychia were generally reduced after dacomitinib dose reductions and dacomitinib treatment duration was generally longer in patients with a dose reduction in comparison with those without a dose reduction. Our results confirmed the efficacy and safety of first-line dacomitinib in Japanese patients with EGFR-positive advanced NSCLC.

摘要

: 在ARCHER 1050 随机 3 期试验的一个日本患者亚组中,我们评估了疗效和安全性,并确定了剂量调整对不良事件 (AE) 的影响和一线口服达克替尼 45 mg与口服吉非替尼 250 mg的治疗管理,在 28 天周期中每日一次,在EGFR激活突变阳性 (EGFR阳性; 外显子 19 缺失或外显子 21 L858R替代突变) 晚期非小细胞肺癌 (NSCLC) 患者中。主要终点为无进展生存期 (PFS; RECIST,1.1 版,盲法独立审查).在 81 例日本患者 (40 例达克替尼,41 例吉非替尼) 中,达克替尼组与吉非替尼组相比PFS更长 (风险比 [HR],0.544 [95% 可信区间 {CI},0.307-0.961]; 双侧P =。0327; 达克替尼的中位数为 18.2 [95% CI,11.0-31.3] mo,9.3 [95% CI,7.4-14.7]Mo为吉非替尼)。最常见的 3 级ae是使用达克替尼的痤疮样皮炎 (27.5%) 和使用吉非替尼的丙氨酸氨基转移酶增加 (12.2%)。与吉非替尼 (85.0%) 相比,接受达克替尼 (24.4%) 的患者发生导致剂量减少的不良事件的比例较高。腹泻的发病率和严重程度,痤疮样皮炎,在dacomitinib剂量减少后,口腔炎和甲沟炎通常减少,并且与未减少剂量的患者相比,减少剂量的患者的dacomitinib治疗持续时间通常更长。我们的研究结果证实了dacomitinib一线治疗日本EGFR阳性晚期NSCLC患者的疗效和安全性。

下载该文献
小狗阅读

帮助医生、学生、科研工作者解决SCI文献找不到、看不懂、阅读效率低的问题。提供领域精准的SCI文献,通过多角度解析提高文献阅读效率,从而使用户获得有价值研究思路。

相关文献
影响因子:1.80
发表时间:2020-01-01
DOI:10.1016/j.athoracsur.2019.04.100
作者列表:["Mammana M","Zuin A","Serra E","Bellini A","Rea F"]

METHODS::Pulmonary artery sling is a rare congenital anomaly of the origin and course of the left pulmonary artery. Patients with this condition typically present with respiratory failure in young infancy, and asymptomatic cases are uncommon. We describe the case of an adult patient with a lung adenocarcinoma of the right upper lobe, extending into the hilum and superior mediastinum, and with a previously unknown pulmonary artery sling anomaly. The local invasiveness of the tumor and the peculiar vascular anatomy contributed to a unique surgical scenario, wherein multiple reconstructive procedures were required.

关键词: 暂无
翻译标题与摘要 下载文献
影响因子:6.93
发表时间:2020-01-15
DOI:10.1002/ijc.32532
作者列表:["Hata A","Nakajima T","Matsusaka K","Fukuyo M","Morimoto J","Yamamoto T","Sakairi Y","Rahmutulla B","Ota S","Wada H","Suzuki H","Matsubara H","Yoshino I","Kaneda A"]

METHODS::Patients with idiopathic pulmonary fibrosis (IPF) have higher risk of developing lung cancer, for example, squamous cell carcinoma (SCC), and show poor prognosis, while the molecular basis has not been fully investigated. Here we conducted DNA methylome analysis of lung SCC using 20 SCC samples with/without IPF, and noncancerous lung tissue samples from smokers/nonsmokers, using Infinium HumanMethylation 450K array. SCC was clustered into low- and high-methylation epigenotypes by hierarchical clustering analysis. Genes hypermethylated in SCC significantly included genes targeted by polycomb repressive complex in embryonic stem cells, and genes associated with Gene Ontology terms, for example, "transcription" and "cell adhesion," while genes hypermethylated specifically in high-methylation subgroup significantly included genes associated with "negative regulation of growth." Low-methylation subgroup significantly correlated with IPF (78%, vs. 17% in high-methylation subgroup, p = 0.04), and the correlation was validated by additional Infinium analysis of SCC samples (n = 44 in total), and data from The Cancer Genome Atlas (n = 390). The correlation between low-methylation subgroup and IPF was further validated by quantitative methylation analysis of marker genes commonly hypermethylated in SCC (HOXA2, HOXA9 and PCDHGB6), and markers specifically hypermethylated in high-methylation subgroup (DLEC1, CFTR, MT1M, CRIP3 and ALDH7A1) in 77 SCC cases using pyrosequencing (p = 0.003). Furthermore, low-methylation epigenotype significantly correlated with poorer prognosis among all SCC patients, or among patients without IPF. Multivariate analysis showed that low-methylation epigenotype is an independent predictor of poor prognosis. These may suggest that lung SCC could be stratified into molecular subtypes with distinct prognosis, and low-methylation lung SCC that significantly correlates with IPF shows unfavorable outcome.

翻译标题与摘要 下载文献
影响因子:6.93
发表时间:2020-01-01
DOI:10.1002/ijc.32530
作者列表:["Zhang L","Yang Y","Chai L","Bu H","Yang Y","Huang H","Ran J","Zhu Y","Li L","Chen F","Li W"]

METHODS::The role of Fyn-related kinase (FRK) in malignant tumors remains controversial. Our study investigated the function of FRK in lung cancer. Immunohistochemistry staining and generating a knockout of FRK by CRISPR/Cas9 in H1299 (FRK-KO-H1299) cells were strategies used to explore the role of FRK. Immunohistochemistry staining indicated that FRK expression was elevated in 223 lung cancer tissues compared to 26 distant normal lung tissues. FRK contributed to poor survival status in lung cancer patients and acted as a predictor for poor prognosis of lung cancer. Knockout of FRK by CRISPR/Cas9 markedly inhibited proliferation, invasion, colony formation and epithelial-mesenchymal transition (EMT) process in the lung cancer cell line H1299. Further exploration indicated that FRK-KO damaged the stemness phenotype of H1299 by inhibiting CD44 and CD133 expression. Seahorse detection and a U-13 C flux assay revealed that FRK-KO induced metabolism reprogramming by inhibiting the Warburg effect and changing the energy type in H1299 cells. Epidermal growth factor stimulation recovered the expression of FRK and biological functions, metabolic reprogramming and stemness phenotype of H1299 cells. FRK plays an oncogenic role in lung cancer cells via a novel regulation mechanism of enhancing the stemness of H1299 cells by inducing metabolism reprogramming, which finally promotes EMT and metastasis. Our study also indicates that FRK could be used as a potential therapeutic target for drug development.

翻译标题与摘要 下载文献
肺肿瘤方向

肺肿瘤,又叫支气管肺癌,是常见的恶性肿瘤之一。肺肿瘤的治疗为包括手术、中药、放疗、化疗及免疫等多学科的综合治疗。

复制标题
发送后即可在该邮箱或我的下载查看该文献
发送
该文献默认存储到我的下载

科研福利

报名咨询

建议反馈
问题标题:
联系方式:
电子邮件:
您的需求: