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Egfr tki

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https://www.readbyqxmd.com/read/28801995/inst-ox-05-024-first-line-gemcitabine-oxaliplatin-and-erlotinib-for-primary-hepatocellular-carcinoma-and-bile-duct-cancers-a-multicenter-phase-ii-trial
#1
Yehuda Z Patt, Waheed Murad, Mohammed H Fekrazad, Ari D Baron, Pranshu Bansal, Yanis Boumber, Kim Steinberg, Sang-Joon Lee, Ed Bedrick, Ruofei Du, Fa Chyi Lee
Hepatocellular Carcinoma (HCC) incidence is increasing in the USA. Gemcitabine (G) and oxaliplatin (O) are active in HCC and biliary duct cancer (BDC). Erlotinib (E) is an EGFR tyrosine kinase inhibitor (TKI) with known activity against both. We sought to evaluate the efficacy of the combination G+O+E. Patients with either of the two diagnosis were treated in a phase II trial. Simons 2 stage design was used. A disease-control rate (DCR), complete response (CR) + partial response (PR)+ stable disease (SD) at 24 weeks of ≤20% and >40% (P0 and P1 of 0...
August 11, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28801183/paired-phase-ii-studies-of-erlotinib-bevacizumab-for-advanced-bronchioloalveolar-carcinoma-or-never-smokers-with-advanced-non-small-cell-lung-cancer-swog-s0635-and-s0636-trials
#2
Howard L West, James Moon, Antoinette J Wozniak, Philip Mack, Fred R Hirsch, Martin J Bury, Myron Kwong, Dorothy D Nguyen, Dennis F Moore, Jieling Miao, Mary Redman, Karen Kelly, David R Gandara
BACKGROUND: Before mutation testing of the epidermal growth factor receptor (EGFR) gene was recognized as highly associated with the activity of EGFR tyrosine kinase inhibitors (TKIs), clinically defined patient populations with bronchioloalveolar carcinoma (BAC) and never smokers were identified as likely to benefit from EGFR TKIs. From preclinical and clinical data suggesting potentially improved efficacy with a combination of an EGFR TKI and the antiangiogenic agent bevacizumab, the Southwestern Oncology Group (SWOG) initiated paired phase II trials to evaluate the combination of erlotinib/bevacizumab in patients with advanced BAC (SWOG S0635) or never smokers with advanced lung adenocarcinoma (SWOG S0636)...
July 6, 2017: Clinical Lung Cancer
https://www.readbyqxmd.com/read/28798090/egfr-tyrosine-kinase-inhibitors-versus-chemotherapy-in-egfr-wild-type-pre-treated-advanced-nonsmall-cell-lung-cancer-in%C3%A2-daily-practice
#3
Pascale Tomasini, Solenn Brosseau, Julien Mazières, Jean-Philippe Merlio, Michèle Beau-Faller, Jean Mosser, Marie Wislez, L'Houcine Ouafik, Benjamin Besse, Isabelle Rouquette, Didier Debieuvre, Fabienne Escande, Virginie Westeel, Clarisse Audigier-Valette, Pascale Missy, Alexandra Langlais, Frank Morin, Denis Moro-Sibilot, Gérard Zalcman, Fabrice Barlesi
Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are approved for second-line treatment of EGFR wild-type (EGFR-wt) nonsmall cell lung cancer (NSCLC). However, results from randomised trials performed to compare EGFR-TKIs with chemotherapy in this population did not show any survival benefit. In the era of immunotherapy, many drugs are approved for second-line treatment of EGFR-wt NSCLC and there is a need to reassess the role of EGFR-TKIs in this setting.The Biomarkers France study is a large nationwide cohort of NSCLC patients tested for EGFR mutations...
August 2017: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
https://www.readbyqxmd.com/read/28794650/treating-egfr-mutation-resistance-in-non-small-cell-lung-cancer-role-of-osimertinib
#4
REVIEW
Valentina Mazza, Federico Cappuzzo
The discovery of mutations in EGFR significantly changed the treatment paradigm of patients with EGFR-mutant non-small cell lung cancer (NSCLC), a particular group of patients with different clinical characteristics and outcome to EGFR-wild-type patients. In these patients, the treatment of choice as first-line therapy is first- or second-generation EGFR-tyrosine kinase inhibitors (EGFR-TKIs), such as gefitinib, erlotinib, or afatinib. Inevitably, after the initial response, all patients become refractory to these drugs...
2017: Application of Clinical Genetics
https://www.readbyqxmd.com/read/28790845/clinical-efficacy-evaluation-of-tyrosine-kinase-inhibitors-for-non-adenocarcinoma-lung-cancer-patients-harboring-egfr-sensitizing-mutations
#5
REVIEW
Xinyu Song, Zhehai Wang
Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) as a standard therapy have been used in EGFR-mutated adenocarcinoma of non-small-cell lung cancer (NSCLC) patients in recent years. But in current randomized prospective clinical trials, due to few cases of non-adenocarcinoma patients having been found, the efficacy of TKIs for EGFR-mutated non-adenocarcinoma and the relationship with clinicopathological characteristics remained debatable. The results of retrospective studies showed that the frequency of EGFR mutation was significantly associated with nationality, gender, smoking history, and histology type...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28782530/chemotherapeutics-resistance-arms-race-an-update-on-mechanisms-involved-in-resistance-limiting-egfr-inhibitors-in-lung-cancer
#6
REVIEW
Pankaj Kumar Singh, Om Silakari
Clinical reports suggest that EGFR-mutated lung cancer usually respond significantly towards small molecule tyrosine kinase inhibitors. Same studies also report the eventual development of acquired resistance within a median time interval of 9 to 14months. One of the major mechanisms involved in this acquired resistance was found to be a secondary point mutation at gate-keeper residue, EGFR T790M. However, there are other recent studies which disclose the role of few other novel key players such as, ZEB1, TOPK etc...
August 4, 2017: Life Sciences
https://www.readbyqxmd.com/read/28781781/responses-to-crizotinib-and-chemotherapy-in-patients-with-lung-adenocarcinoma-harboring-a-concomitant-egfr-mutation-and-alk-gene-rearrangement-a-case-report-and-review-of-the-literature
#7
Yuping Li, Shanshan Su, Guoping Cai, Quan Lin, Ying Zhou, Jinsheng Ouyang, Bicheng Chen, Junru Ye, Xiuling Wu, Chengshui Chen
Previous studies have indicated that, in lung cancers, the gene rearrangement of ALK is mutually exclusive with mutations in the epidermal growth factor receptor (EGFR) gene. However, the coexistence of EML4-ALK fusions and EGFR mutations (double positive) has been occasionally reported, with frequencies ranging from 0-8%. Currently, no consensus standard therapy exists for tumors with double positive mutations. In the present case report, the case is described of a 53-year-old woman with stage IV lung adenocarcinoma, harboring a concomitant EGFR mutation and ALK gene rearrangement, who was refractory to gefitinib administration but demonstrated a good response to crizotinib and pemetrexed chemotherapy...
August 2017: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/28779874/brief-report-met-exon-14-alterations-and-new-resistance-mutations-to-tyrosine-kinase-inhibitors-risk-of-inadequate-detection-with-current-amplicon-based-ngs-panels
#8
Brigitte Poirot, Ludovic Doucet, Shirine Benhenda, Jérôme Champ, Véronique Meignin, Jacqueline Lehmann-Che
INTRODUCTION: Targeted therapies, as tyrosine kinase inhibitors (TKI), have dramatically improved the treatment of lung adenocarcinoma and detection of activating mutations of genes like EGFR or ALK is now mandatory in clinical setting. However, additional targetable alterations are continuously described and force us to adapt our detection methods. We evaluate here the ability of 8 amplicon-based next generation sequencing (NGS) panels to detect the recently described MET exon 14 alterations or new resistance-mutations to TKI...
August 2, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28777825/beyond-disease-progression-clinical-outcomes-after-egfr-tkis-in-a-cohort-of-egfr-mutated-nsclc-patients
#9
Roxana Alina Tudor, Adrijana D'Silva, Alain Tremblay, Paul MacEachern, Don Morris, Darren Brenner, Karen Kopciuk, Dafydd Gwyn Bebb
PURPOSE: Treatment and clinical-outcomes were described in a sub-cohort of non-small-cell lung cancer (NSCLC) patients with disease-progression (PD) after epidermal growth factor tyrosine kinase inhibitors (EGFR-TKIs) treatment. PATIENTS AND METHODS: We retrospectively analyzed a single-institutional EGFR mutation positive (EGFRmut+) NSCLC cohort for post-TKI-PD management, and assessed overall survival (OS) and post-progression survival (PPS). All de-novo (first lung-cancer occurrence) stage IIIA-IV patients, as well as de-novo stage IV subset was analyzed...
2017: PloS One
https://www.readbyqxmd.com/read/28776311/continued-egfr-tki-with-concurrent-radiotherapy-to-improve-time-to-progression-ttp-in-patients-with-locally-progressive-non-small-cell-lung-cancer-nsclc-after-front-line-egfr-tki-treatment
#10
Y Wang, Y Li, L Xia, K Niu, X Chen, D Lu, R Kong, Z Chen, J Sun
BACKGROUND: Epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) is the optimal treatment for EGFR-mutant advanced non-small cell lung cancer (NSCLC). However, most patients developed systemic or local progression due to acquired EGFR-TKI resistance. This retrospective study aimed to evaluate the feasibility of continued EGFR-TKI with concurrent radiotherapy (CTCRT) in patients with local progression after front-line EGFR-TKI treatment. METHODS: Advanced NSCLC patients with active EGFR mutation who received EGFR-TKI were treated with CTCRT after local progression...
August 3, 2017: Clinical & Translational Oncology
https://www.readbyqxmd.com/read/28774798/drug-combination-approach-to-overcome-resistance-to-egfr-tyrosine-kinase-inhibitors-in-lung-cancer
#11
Christy W S Tong, William K K Wu, Herbert H F Loong, William C S Cho, Kenneth K W To
The discovery of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI) has led to unprecedented clinical response in a subset of lung cancer patients carrying the sensitizing EGFR mutations (L858R or exon 19 deletion). However, disease progression invariably occurs within a year after the initial TKI treatment, predominantly due to the development of acquired resistance caused by the secondary EGFR T790 M mutation. Numerous second generation irreversible and third generation EGFR T790 M selective EGFR TKIs have been developed to overcome resistance...
July 31, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28768973/histological-transformation-to-large-cell-neuroendocrine-carcinoma-from-lung-adenocarcinoma-harboring-an-egfr-mutation-an-autopsy-case-report
#12
Rika Moriya, Satoshi Hokari, Satoshi Shibata, Takeshi Koizumi, Takafumi Tetsuka, Kazuhiko Ito, Hideki Hashidate, Hiroki Tsukada
We herein report a 58-year-old Japanese woman who survived 14 years after surgery for lung adenocarcinoma harboring an epidermal growth factor receptor (EGFR) exon 19 deletion. She developed recurrence, for which she underwent multimodal therapy, including EGFR-tyrosine kinase inhibitor (TKI) administration. She ultimately died from a rapidly progressive right lung tumor that was resistant to EGFR-TKI. According to the autopsy findings, she had combined large-cell neuroendocrine carcinoma (LCNEC) and adenocarcinoma in the right lung, which retained an EGFR exon 19 deletion in both components...
2017: Internal Medicine
https://www.readbyqxmd.com/read/28767402/mimicking-the-bim-bh3-domain-overcomes-resistance-to-egfr-tyrosine-kinase-inhibitors-in-egfr-mutant-non-small-cell-lung-cancer
#13
Jinjing Xia, Hao Bai, Bo Yan, Rong Li, Minhua Shao, Liwen Xiong, Baohui Han
Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) are widely applied to treat EGFR-mutant non-small cell lung cancer (NSCLC). BIM is a BH3 domain-containing protein encoded by BCL2L11. Some EGFR-mutant NSCLC patients showing BIM deletion polymorphism are resistant to EGFR TKIs. We retrospectively investigated BIM deletion polymorphism in NSCLC patients, its correlation with EGFR TKI (erlotinib) resistance, and the mechanism underlying the drug resistance. Among 245 EGFR-mutant NSCLC patients examined, BIM deletion polymorphism was detected in 43 (12...
July 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/28766870/extracellular-hyaluronic-acid-influences-the-efficacy-of-egfr-tyrosine-kinase-inhibitors-in-a-biomaterial-model-of-glioblastoma
#14
Sara Pedron, Jacob S Hanselman, Mark A Schroeder, Jann N Sarkaria, Brendan A C Harley
3D biomaterial models have potential to explore the influence of the tumor microenvironment on aberrant signaling pathways and compensatory signals using patient-derived cells. Glioblastoma (GBM) tumors are highly heterogeneous, with both cell composition and extracellular matrix biophysical factors seen as key regulators of malignant phenotype and treatment outcomes. Amplification, overexpression, and mutation of the epidermal growth factor receptor (EGFR) tyrosine kinase have been identified in 50% of GBM patients...
August 2, 2017: Advanced Healthcare Materials
https://www.readbyqxmd.com/read/28762087/non-small-cell-lung-cancer-nsclc-harboring-alk-translocations-clinical-characteristics-and-management-in-a-real-life-setting-a-french-retrospective-analysis-gfpc-02-14-study
#15
Jean-Bernard Auliac, Isabelle Monnet, Catherine Dubos-Arvis, Anne Marie Chiappa, Nathalie Baize, Suzana Bota, Alain Vergnenegre, Helene Doubre, Chrystele Locher, Acya Bizieux, Gilles Robinet, Christos Chouaid
BACKGROUND: Chromosomal translocations involving the anaplastic lymphoma kinase gene (ALK) are rare oncogenic events found in 3-5% of non-small-cell lung cancers (NSCLC). Limited data have been published on the management of these patients outside clinical trials. OBJECTIVE: To investigate the clinical characteristics and management of patients with NSCLC harboring ALK translocations (ALK+) in a real-life setting in France. METHODS: This multicenter, observational, retrospective study included all NSCLC patients harboring ALK translocations diagnosed in participating centers between January 2012 and December 2014...
July 31, 2017: Targeted Oncology
https://www.readbyqxmd.com/read/28758857/brain-metastases-in-non-small-cell-lung-cancer-patients-on-epidermal-growth-factor-receptor-tyrosine-kinase-inhibitors-symptom-and-economic-burden
#16
Ancilla W Fernandes, Bingcao Wu, Ralph M Turner
OBJECTIVE: This study describes the symptom and economic burden associated with brain metastases (BM) in patients with non-small cell lung cancer (NSCLC) receiving epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (EGFR-TKIs). METHODS: This retrospective study included adults with ≥2 medical claims, within 90 days, for lung cancer and ≥1 administration of EGFR-TKIs. Based on ICD-9 codes, patients were stratified into cohorts by type of metastases (BM, other metastases [OM], or no metastases [NM]), and by when the metastasis diagnosis occurred (synchronous or asynchronous)...
July 31, 2017: Journal of Medical Economics
https://www.readbyqxmd.com/read/28757172/polyphyllin-vii-increases-sensitivity-to-gefitinib-by-modulating-the-elevation-of-p21-in-acquired-gefitinib-resistant-non-small-cell-lung-cancer
#17
Honggang Wang, Zhenghua Fei, Hao Jiang
Blockade of EGFR with reversible EGFR tyrosine kinase inhibitors (TKIs) is considered the frontline strategy for advanced NSCLC with EGFR mutations. However, acquired resistance to EGFR-TKI has been observed, resulting in disease progression and limited clinical benefit. Polyphyllin VII is the main member of polyphyllin family, which has been demonstrated to show strong anticancer activity against carcinomas. The sensitizing effect and underlying mechanism of Polyphyllin VII against acquired EGFR-TKI resistant NSCLC are still unexplored...
June 30, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28756224/treatment-with-a-programmed-cell-death-1-specific-antibody-has-little-effect-on-afatinib-and-naphthalene-induced-acute-pneumonitis-in-mice
#18
Naoki Hamada, Toyoshi Yanagihara, Kunihiro Suzuki, Saiko Ogata-Suetsugu, Eiji Harada, Hironori Mikumo, Masako Arimura-Omori, Yoichi Nakanishi
Although several antibodies developed to target programmed cell death-1 (PD-1) and its ligand (PD-L1) have demonstrated great promise for the treatment of non-small cell lung cancer (NSCLC), and other malignancies, these therapeutic antibodies can cause pneumonitis. Furthermore, epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI)-induced pneumonitis was reported after treatment with anti PD-1 antibodies. We previously demonstrated that mice with naphthalene-induced airway epithelial injury developed severe gefitinib-induced pneumonitis through a neutrophil-dependent mechanism...
July 27, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28751247/brief-report-modulation-of-biomarker-expression-by-osimertinib-results-of-the-paired-tumor-biopsy-cohorts-of-the-aura-phase-i-trial
#19
Kenneth S Thress, Vivien Jacobs, Helen K Angell, James Chih-Hsin Yang, Lecia V Sequist, Fiona Blackhall, Wu-Chou Su, Martin Schuler, Jürgen Wolf, Kathryn A Gold, Mireille Cantarini, J Carl Barrett, Pasi A Jänne
INTRODUCTION: Osimertinib is an oral, potent, irreversible epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) selective for EGFR-TKI and T790M resistance mutations. To enhance understanding of osimertinib's mechanism of action, we aimed to evaluate the modulation of key molecular biomarkers post-osimertinib in paired clinical samples from the Phase I AURA trial. METHODS: Paired tumor biopsies were collected pre-study and following 15±7 days of osimertinib treatment (80 or 160 mg daily)...
July 24, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28749535/inhibition-of-histone-deacetylases-sensitizes-egfr-tki-resistant-non-small-cell-lung-cancer-cells-to-erlotinib-in-vitro-and-in-vivo
#20
Weiwei Yu, Weiqiang Lu, Guoliang Chen, Feixiong Cheng, Hui Su, Yihua Chen, Mingyao Liu, Xiufeng Pang
BACKGROUND AND PURPOSE: Intrinsic and/or acquired resistance of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) commonly occurs in patients with non-small-cell lung cancer (NSCLC). Here, we develop a combined therapy of histone deacetylase inhibition by a novel HDAC inhibitor, YF454A, with erlotinib to overcome EGFR-TKI resistance in NSCLC. EXPERIMENTAL APPROACH: The sensitization of erlotinib by YF454A was examined in a panel of EGFR-TKI-resistant NSCLC cell lines in vitro and two different erlotinib-resistant NSCLC xenograft mouse models in vivo...
July 27, 2017: British Journal of Pharmacology
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