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Egfr tki

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https://www.readbyqxmd.com/read/28734822/icotinib-versus-whole-brain-irradiation-in-patients-with-egfr-mutant-non-small-cell-lung-cancer-and-multiple-brain-metastases-brain-a-multicentre-phase-3-open-label-parallel-randomised-controlled-trial
#1
Jin-Ji Yang, Caicun Zhou, Yisheng Huang, Jifeng Feng, Sun Lu, Yong Song, Cheng Huang, Gang Wu, Li Zhang, Ying Cheng, Chengping Hu, Gongyan Chen, Li Zhang, Xiaoqing Liu, Hong Hong Yan, Fen Lai Tan, Wenzhao Zhong, Yi-Long Wu
BACKGROUND: For patients with non-small-cell lung cancer (NSCLC) and multiple brain metastases, whole-brain irradiation (WBI) is a standard-of-care treatment, but its effects on neurocognition are complex and concerning. We compared the efficacy of an epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI), icotinib, versus WBI with or without chemotherapy in a phase 3 trial of patients with EGFR-mutant NSCLC and multiple brain metastases. METHODS: We did a multicentre, open-label, parallel randomised controlled trial (BRAIN) at 17 hospitals in China...
July 19, 2017: Lancet Respiratory Medicine
https://www.readbyqxmd.com/read/28733559/dynamics-of-egfr-mutations-in-plasma-recapitulates-the-clinical-response-to-egfr-tkis-in-nsclc-patients
#2
Liwen Xiong, Shaohua Cui, Jingyan Ding, Yun Sun, Longfu Zhang, Yizhuo Zhao, Aiqin Gu, Tianqing Chu, Huimin Wang, Hua Zhong, Xin Ye, Yi Gu, Xin Zhang, Min Hu, Liyan Jiang
OBJECTIVES: Genomic profiling using plasma cell-free DNA (cfDNA) represents a non-invasive alternative to tumor re-biopsy, which is challenging in clinical practice. The feasibility of dynamically monitoring epidermal growth factor receptor (EGFR) mutation status using serial plasma samples from non-small cell lung cancer (NSCLC) patients treated by tyrosine kinase inhibitors (TKIs) and its application in tracking clinical response and detection of resistance were investigated. PATIENTS AND METHODS: Forty-five NSCLC patients with EGFR mutation-positive pre-TKI plasma and at least two post-TKI plasma collections were recruited to this study...
July 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28730963/increased-expression-of-ire1%C3%AE-associates-with-the-resistant-mechanism-of-osimertinib-azd9291-resistant-non-small-cell-lung-cancer-hcc827-osir-cells
#3
Zheng-Hai Tang, Min-Xia Su, Xia Guo, Xiao-Ming Jiang, Lin Jia, Xiuping Chen, Jin-Jian Lu
BACKGROUND: Osimertinib (OSI), also known as AZD9291, is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that has been approved for the treatment of non-small cell lung cancer (NSCLC) patients. OBJECTIVE: Establishment of the OSI-resistant HCC827/OSIR cell line and study of its resistant mechanism. METHOD: The anti-proliferative effect was studied through MTT and colony formation assays. The protein expression was detected by Western blot assay...
July 19, 2017: Anti-cancer Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/28721096/comparison-of-gefitinib-as-first-and-second-line-therapy-for-advanced-lung-adenocarcinoma-patients-with-positive-exon-21-or-19-del-epidermal-growth-factor-receptor-mutation
#4
Nishant Patel, Pingping Wu, Haijun Zhang
OBJECTIVES: Gefitinib, a tyrosine kinase inhibitor (TKI) targeting epidermal growth factor receptor (EGFR), shows excellent clinical benefit in treating advanced non-small-cell lung cancer (NSCLC). The aim of this study was to compare the efficacy and toxicity of gefitinib as first-line therapy and second-line therapy for advanced lung adenocarcinoma patients with positive exon 21 (L858R) or exon 19 deletion of EGFR mutation. METHODS: We retrospectively analyzed the clinical data of 60 EGFR-mutated advanced lung adenocarcinoma patients from July 2011 to November 2015 who have received oral gefitinib 250 mg once daily...
2017: Cancer Management and Research
https://www.readbyqxmd.com/read/28719349/identification-of-g2607a-mutation-in-egfr-gene-with-a-significative-rate-in-moroccan-patients-with-bladder-cancer
#5
W El Hamdani, K Hadami, M Bensaid, H El Ahanidi, A Ameur, A Filali Maltouf, M Abbar, M Attaleb, A Albouzidi, M El Mzibri
The epidermal growth factor receptor (EGFR) is involved in the regulation of several cellular processes and in the development of many human cancers. Somatic mutations of EGFR at tyrosine kinase domain have been associated with clinical response to tyrosine kinase inhibitors (TKIs) in lung cancer patients. In this study, we evaluated the frequency of point mutations in EGFR for future use of TKI in clinical treatment of bladder cancer. A total, 50 Moroccan patient specimens with bladder cancer and 48 healthy controls were analysed for EGFR mutations in the region delimiting exons 18-21 by PCR amplification and direct sequencing...
May 20, 2017: Cellular and Molecular Biology
https://www.readbyqxmd.com/read/28718011/case-series-on-the-association-between-blood-levels-and-side-effects-of-afatinib-maleate
#6
Junya Sato, Naoto Morikawa, Ryosuke Chiba, Satoru Nihei, Satoshi Moriguchi, Heisuke Saito, Kohei Yamauchi, Kenzo Kudo
PURPOSE: Afatinib maleate (AFA) is a second-generation, tyrosine kinase inhibitor (TKI) treatment for specific variants of non-small cell lung cancer exhibiting epidermal growth factor receptor (EGFR) mutations. In this study, we measured the blood AFA levels in six patients with lung cancer and investigated the association between blood levels and side effects of this drug. METHODS: The study subjects were patients who were administered AFA for non-small cell lung cancer...
July 17, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28717642/lung-adenocarcinoma-patients-of-young-age-have-lower-egfr-mutation-rate-and-poorer-efficacy-of-egfr-tyrosine-kinase-inhibitors
#7
Shang-Gin Wu, Yih-Leong Chang, Chong-Jen Yu, Pan-Chyr Yang, Jin-Yuan Shih
Patients aged ≤50 years are rarely diagnosed with nonsmall cell lung cancer. We conducted a retrospective cohort study to understand the mutation status of EGFR and the efficacy of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) treatment in young Asian patients with lung adenocarcinoma. We collected tumour specimens and malignant pleural effusions from lung adenocarcinoma patients from June 2005 to April 2014, recorded their clinical demographic data, and analysed EGFR mutations by reverse transcriptase PCR...
July 2017: ERJ Open Research
https://www.readbyqxmd.com/read/28717073/interstitial-lung-disease-after-pleurodesis-for-malignant-pleural-effusion
#8
Norihito Yokoe, Eisuke Katsuda, Kenshi Kosaka, Rie Hamanaka, Ayako Matsubara, Masaki Nishimura, Hiroyuki Tanaka, Nobuhiro Asai, Ayumu Takahashi, Toshiki Kawamura, Tsuneo Ishiguchi, Etsuro Yamaguchi, Akihito Kubo
Objective Pleurodesis is an effective therapy for malignant pleural effusion (MPE). While interstitial lung disease (ILD) has been regarded as a serious complication of pleurodesis, its clinicopathological characteristics have not been fully understood. This study was conducted to elucidate the incidence of ILD and the risk factors for ILD in patients who underwent pleurodesis to control MPE. Methods The medical records of patients who underwent pleurodesis in Aichi Medical University between March 2008 and February 2013, the period before the approval of talc in Japan, were retrospectively analyzed...
2017: Internal Medicine
https://www.readbyqxmd.com/read/28712979/clinical-implications-of-the-t790m-mutation-in-disease-characteristics-and-treatment-response-in-patients-with-epidermal-growth-factor-receptor-egfr-mutated-non-small-cell-lung-cancer%C3%A2-nsclc
#9
Daria Gaut, Myung Shin Sim, Yuguang Yue, Brian R Wolf, Phillip A Abarca, James M Carroll, Jonathan W Goldman, Edward B Garon
BACKGROUND: The secondary T790M mutation accounts for more than 50% of acquired tyrosine kinase inhibitor (TKI) resistance in patients with EGFR-mutated non-small-cell lung cancer (NSCLC). Recent reports suggest this resistance mutation may be more common among patients with longer progression-free survival (PFS) on first-line TKI therapy, but much is still unknown. MATERIALS AND METHODS: Our group collected medical records from patients who underwent a biopsy for T790M mutation testing while screening for clinical trials involving the drug rociletinib (CO-1686), a T790M mutation-specific TKI...
June 20, 2017: Clinical Lung Cancer
https://www.readbyqxmd.com/read/28710746/osimertinib-a-review-in-t790m-positive-advanced-non-small-cell-lung-cancer
#10
REVIEW
Yvette N Lamb, Lesley J Scott
Osimertinib (Tagrisso™) is an oral, CNS-active, third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that targets EGFR TKI-sensitizing mutations and, crucially, the T790M mutation that often underlies acquired resistance to EGFR TKI therapy. Osimertinib has been approved in numerous countries for use in patients with T790M-positive advanced NSCLC. In the pivotal, international AURA3 trial in patients with T790M-positive advanced NSCLC who had disease progression after EGFR TKI therapy, osimertinib treatment significantly prolonged progression-free survival (PFS; primary endpoint) compared with platinum-pemetrexed therapy at the time of the primary analysis...
July 14, 2017: Targeted Oncology
https://www.readbyqxmd.com/read/28708233/treatment-in-egfr-mutated-non-small-cell-lung-cancer-how-to-block-the-receptor-and-overcome-resistance-mechanisms
#11
Claudia Proto, Giuseppe Lo Russo, Giulia Corrao, Monica Ganzinelli, Francesco Facchinetti, Roberta Minari, Marcello Tiseo, Marina Chiara Garassino
In non-small cell lung cancer (NSCLC), the identification of epidermal growth factor receptor (EGFR) mutations and the parallel development of EGFR tyrosine kinase inhibitors (TKIs) have radically changed the therapeutic management strategies. Currently, erlotinib, gefitinib, and afatinib are all approved as standard first-line treatment in EGFR-mutated NSCLC. However, despite the proven efficacy, some EGFR-mutated NSCLCs do not respond to EGFR TKIs, while some patients, after a favorable and prolonged response to EGFR TKIs, inevitably progress within about 10-14 months...
July 1, 2017: Tumori
https://www.readbyqxmd.com/read/28706139/a-phase-i-study-of-foretinib-plus-erlotinib-in-patients-with-previously-treated-advanced-non-small-cell-lung-cancer-canadian-cancer-trials-group-ind-196
#12
Natasha B Leighl, Ming-Sound Tsao, Geoffrey Liu, Dongsheng Tu, Cheryl Ho, Frances A Shepherd, Nevin Murray, John R Goffin, Garth Nicholas, Shingo Sakashita, Zhuo Chen, Lucia Kim, Jean Powers, Lesley Seymour, Glenwood Goss, Penelope A Bradbury
PURPOSE: MET and AXL mediate resistance to EGFR TKI in NSCLC. Foretinib, a MET/RON/AXL/TIE-2/VEGFR kinase inhibitor may overcome EGFR kinase resistance. This dose escalation study combined foretinib and erlotinib in advanced pretreated NSCLC patients. EXPERIMENTAL DESIGN: The primary endpoint was to define the RP2D of foretinib plus erlotinib as continuous oral daily dosing. Secondary objectives included safety, pharmacokinetics, response and potential biomarkers of response including EGFR, KRAS genotype, MET, AXL expression, and circulating HGF levels...
June 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28705152/elevated-serum-cea-levels-are-associated-with-the-explosive-progression-of-lung-adenocarcinoma-harboring-egfr-mutations
#13
Yuan Gao, PingPing Song, Hui Li, Hui Jia, BaiJiang Zhang
BACKGROUND: Serum carcinoembryonic antigen (CEA) levels are a predictor of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) efficacy and are associated with epidermal growth factor receptor (EGFR) gene mutations. However, the clinical significance of plasma CEA level changes during different cycles of target therapy is unknown for lung adenocarcinoma patients with sensitizing EGFR mutations. METHODS: In total, 155 patients with lung adenocarcinoma were enrolled in this retrospective study between 2011 and 2015...
July 14, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28704781/impacts-of-egfr-mutation-and-egfr-tkis-on-incidence-of-brain-metastases-in-advanced-non-squamous-nsclc
#14
Bao-Xiao Wang, Wei Ou, Xiao-Yong Mao, Zui Liu, Hui-Qi Wu, Si-Yu Wang
OBJECTIVE: Brain metastases remain lethal in lung cancer patients. The impacts of epidermal growth factor receptor (EGFR) mutations and EGFR tyrosine kinase inhibitors (TKIs) on the incidence of brain metastases in patients with advanced non-squamous non-small cell lung cancer (NSCLC) are still uncertain. PATIENTS AND METHODS: A total of 1672 patients with advanced non-squamous NSCLC with a definitive report on EGFR mutation status between January 2005 and June 2013 were retrospectively analyzed...
June 29, 2017: Clinical Neurology and Neurosurgery
https://www.readbyqxmd.com/read/28701107/overcoming-resistance-to-egfr-tyrosine-kinase-inhibitors-in-lung-cancer-focusing-on-non-t790m-mechanisms
#15
Kenichi Suda, Christopher J Rivard, Tetsuya Mitsudomi, Fred R Hirsch
Despite initial dramatic efficacy of EGFR tyrosine kinase inhibitors (TKIs) in EGFR-mutant lung cancer patients, emergence of acquired resistance is almost inevitable. The EGFR T790M secondary mutation that accounts for ~50% of resistance is now treatable with osimertinib. However, for the remaining 50% of patients who develop resistance mechanisms other than T790M mutation, cytotoxic chemotherapies are still the standard of care and novel treatment strategies are urgently needed. Areas covered: In this review, we discuss current experimental and clinical evidence to develop better treatment strategies to overcome or prevent acquired resistance to EGFR-TKIs in lung cancers, focusing on non-T790M mechanisms...
July 13, 2017: Expert Review of Anticancer Therapy
https://www.readbyqxmd.com/read/28699260/australian-recommendations-for-egfr-t790m-testing-in-advanced-non-small-cell-lung-cancer
#16
REVIEW
Thomas John, Jeffrey J Bowden, Stephen Clarke, Stephen B Fox, Kerryn Garrett, Keith Horwood, Christos S Karapetis
First-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are used as first-line therapy in patients with non-small cell lung cancer (NSCLC) harboring a sensitizing mutation in the EGFR gene. Unfortunately, resistance to these therapies often occurs within 10 months of commencing treatment and is mostly commonly due to the development of the EGFR T790M mutation. Treatment with the third-generation EGFR TKI, osimertinib can prolong progression free survival in patients with the T790M mutation, so it is important to determine the resistance mechanism in order to plan ongoing therapeutic strategies...
July 12, 2017: Asia-Pacific Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28699084/egfr-mutation-testing-of-non-squamous-nsclc-impact-and-uptake-during-implementation-of-testing-guidelines-in-a-population-based-registry-cohort-from-northern-new-zealand
#17
Mark McKeage, Mark Elwood, Sandar Tin Tin, Prashannata Khwaounjoo, Phyu Aye, Angie Li, Karen Sheath, Phillip Shepherd, George Laking, Nicola Kingston, Christopher Lewis, Donald Love
BACKGROUND: Since 2013, clinical practice guidelines recommend EGFR mutation testing of non-squamous NSCLC to select advanced-stage patients for first-line treatment using EGFR-TKIs. OBJECTIVE: We aimed to determine population-based trends in the real-world uptake and impact in routine practice of these recently updated testing guidelines. PATIENTS AND METHODS: A population-based observational study was conducted of notifications to the New Zealand Cancer Registry of patients eligible for EGFR testing diagnosed in northern New Zealand between January 2010 and April 2014...
July 11, 2017: Targeted Oncology
https://www.readbyqxmd.com/read/28693210/resistance-to-epithelial-growth-factor-receptor-tyrosine-kinase-inhibitors-in-a-patient-with-transformation-from-lung-adenocarcinoma-to-small-cell-lung-cancer-a-case-report
#18
Liying Fang, Jian He, Jingwen Xia, Liang Dong, Xiujuan Zhang, Yaqin Chai, Ying Li, Mengjie Niu, Tianxing Hang, Shengqing Li
First-generation epithelial growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have markedly improved the treatment of non-small cell lung cancer (non-SCLC) with EGFR-sensitive mutations. However, acquired resistance to these drugs was inevitable. The transformation of lung adenocarcinoma to SCLC following treatment with EGFR-TKIs is a rare phenomenon that contributes to resistance to EGFR-TKIs. The present case concerns a 74-year-old man previously diagnosed with and treated for pneumonia; however, this was later pathologically confirmed as lung adenocarcinoma by transbronchial lung biopsy...
July 2017: Oncology Letters
https://www.readbyqxmd.com/read/28685062/the-level-of-serum-carcinoembryonic-antigen-is-a-surrogate-marker-for-the-efficacy-of-egfr-tkis-but-is-not-an-indication-of-acquired-resistance-to-egfr-tkis-in-nsclc-patients-with-egfr-mutationsm
#19
Jingquan Han, Yuzhang Li, Shouqiang Cao, Qing Dong, Guibin Zhao, Xiangyu Zhang, Jian Cui
The aim of the present study was to define the relationship between carcinoembryonic antigen (CEA) and survival in non-small cell lung cancer (NSCLC) patients receiving epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) and to investigate whether the level of serum CEA is related to the mechanism for acquisition of resistance to EGFR-TKIs. A total of 100 patients with advanced NSCLC (stage IIIB or stage IV) and harboring EGFR mutations were included. All patients received erlotinib or gefitinib treatment...
July 2017: Biomedical Reports
https://www.readbyqxmd.com/read/28684780/retinoic-acid-affects-lung-adenocarcinoma-growth-by-inducing-differentiation-via-gata6-activation-and-egfr-and-wnt-inhibition
#20
Giovanni Zito, Flores Naselli, Laura Saieva, Stefania Raimondo, Giovanna Calabrese, Claudio Guzzardo, Stefano Forte, Christian Rolfo, Rosalba Parenti, Riccardo Alessandro
A fundamental task in cancer research aims at the identification of new pharmacological therapies that can affect tumor growth. Differentiation therapy might exploit this function not only for hematological diseases, such as acute promyelocytic leukemia (APML) but also for epithelial tumors, including lung cancer. Here we show that Retinoic Acid (RA) arrests in vitro and in vivo the growth of Tyrosine Kinase Inhibitors (TKI) resistant Non Small Cell Lung Cancer (NSCLC). In particular, we found that RA induces G0/G1 cell cycle arrest in TKI resistant NSCLC cells and activates terminal differentiation programs by modulating the expression of GATA6, a key transcription factor involved in the physiological differentiation of the distal lung...
July 6, 2017: Scientific Reports
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