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Erlotinib

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https://www.readbyqxmd.com/read/29455650/management-of-acquired-resistance-to-egfr-tki-targeted-therapy-in-advanced-non-small-cell-lung-cancer
#1
REVIEW
Shang-Gin Wu, Jin-Yuan Shih
Recent advances in diagnosis and treatment are enabling a more targeted approach to treating lung cancers. Therapy targeting the specific oncogenic driver mutation could inhibit tumor progression and provide a favorable prognosis in clinical practice. Activating mutations of epidermal growth factor receptor (EGFR) in non-small cell lung cancer (NSCLC) are a favorable predictive factor for EGFR tyrosine kinase inhibitors (TKIs) treatment. For lung cancer patients with EGFR-exon 19 deletions or an exon 21 Leu858Arg mutation, the standard first-line treatment is first-generation (gefitinib, erlotinib), or second-generation (afatinib) TKIs...
February 19, 2018: Molecular Cancer
https://www.readbyqxmd.com/read/29455554/synthesis-antitumour-and-antioxidant-activities-of-novel-%C3%AE-%C3%AE-unsaturated-ketones-and-related-heterocyclic-analogues-egfr-inhibition-and-molecular-modelling-study
#2
Walaa M El-Husseiny, Magda A-A El-Sayed, Naglaa I Abdel-Aziz, Adel S El-Azab, Esam R Ahmed, Alaa A-M Abdel-Aziz
New α,β-unsaturated ketones 4a,b; 5a-c; and 6a,b; as well as 4-H pyran 7; pyrazoline 8a,b; isoxazoline 9; pyridine 10-11; and quinoline-4-carboxylic acid 12a,b derivatives were synthesized and evaluated for in vitro antitumour activity against HepG2, MCF-7, HeLa, and PC-3 cancer cell lines. Antioxidant activity was investigated by the ability of these compounds to scavenge the 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) radical cation (ABTS•+ ). Compounds 6a, 6b, 7, and 8b exhibited potent antitumour activities against all tested cell lines with [IC50 ] ≅5...
December 2018: Journal of Enzyme Inhibition and Medicinal Chemistry
https://www.readbyqxmd.com/read/29453759/systemic-treatment-of-patients-with-advanced-unresectable-hepatocellular-carcinoma-emergence-of-therapies
#3
REVIEW
Weijing Sun, Roniel Cabrera
To date, sorafenib, a multiple tyrosine kinase inhibitor, is the only systemic agent approved by the FDA in the first-line treatment of patients with unresectable hepatocellular carcinoma (HCC). Several other tyrosine kinase-inhibiting agents have been investigated in the first-line setting, either alone (sunitinib, brivanib, linifanib, and lenvatinib) or in combination with sorafenib (erlotinib and doxorubicin) in phase 3 trials. However, none of these studies demonstrated an improvement in survival over sorafenib...
February 17, 2018: Journal of Gastrointestinal Cancer
https://www.readbyqxmd.com/read/29453635/monitoring-of-erlotinib-in-pancreatic-cancer-patients-during-long-time-administration-and-comparison-to-a-physiologically-based-pharmacokinetic-model
#4
Andrea Gruber, Martin Czejka, Philipp Buchner, Marie Kitzmueller, Nairi Kirchbaumer Baroian, Christian Dittrich, Azra Sahmanovic Hrgovcic
PURPOSE: In this study, a therapeutic drug monitoring (TDM) of erlotinib in pancreatic cancer patients was performed over 50 weeks to reveal possible alterations in erlotinib plasma concentrations. Additionally, a physiologically based pharmacokinetic (PBPK) model was created to assess such variations in silico. METHODS: Patients with advanced pancreatic cancer received a chemotherapeutic combination of 100 mg erlotinib q.d., 500-900 mg capecitabine b.d. and 5 mg/kg bevacizumab q...
February 16, 2018: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/29449529/gambogenic-acid-inhibits-fibroblast-growth-factor-receptor-signaling-pathway-in-erlotinib-resistant-non-small-cell-lung-cancer-and-suppresses-patient-derived-xenograft-growth
#5
Linfeng Xu, Xiaoxiao Meng, Naihan Xu, Wenwei Fu, Hongsheng Tan, Li Zhang, Qianjun Zhou, Jianan Qian, Shiwei Tu, Xueting Li, Yuanzhi Lao, Hongxi Xu
Erlotinib resistance causes a high degree of lethality in non-small-cell lung cancer (NSCLC) patients. The high expression and activation of several receptor tyrosine kinases, such as JAK/STAT3, c-Met, and EGFR, play important roles in drug resistance. The development of tyrosine kinase inhibitors is urgently required in the clinic. Our previous study found that Gambogenic acid (GNA), a small molecule derived from the traditional Chinese medicine herb gamboge, induced cell death in several NSCLC cell lines through JAK/STAT3 inhibition...
February 15, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29448920/the-t790m-resistance-mutation-in-egfr-is-only-found-in-cfdna-from-erlotinib-treated-nsclc-patients-that-harbored-an-activating-egfr-mutation-before-treatment
#6
Christina Demuth, Anne Tranberg Madsen, Britta Weber, Lin Wu, Peter Meldgaard, Boe Sandahl Sorensen
BACKGROUND: Lung cancer patients with an activating mutation in the EGFR (epidermal growth factor receptor) can develop resistance to erlotinib treatment, which is often mediated by the T790M resistance mutation in EGFR. The difficulties in obtaining biopsies at progression make it challenging to investigate the appearance of the T790M mutation at progression in large patient cohorts. We have used cell free DNA (cfDNA) from patients treated with erlotinib to investigate if the development of a T790M mutation coincides with the presence of an activating EGFR mutation in the pre-treatment blood sample...
February 15, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29443782/putative-lung-adenocarcinoma-with-epidermal-growth-factor-receptor-mutation-presenting-as-carcinoma-of-unknown-primary-site-a-case-report
#7
Masahiro Yamasaki, Kunihiko Funaishi, Naomi Saito, Ayaka Sakano, Megumu Fujihara, Wakako Daido, Sayaka Ishiyama, Naoko Deguchi, Masaya Taniwaki, Nobuyuki Ohashi, Noboru Hattori
RATIONALE: Only a few cases of putative lung adenocarcinoma presenting as carcinoma of unknown primary site (CUP) with epidermal growth factor receptor (EGFR) mutation have been reported, and the efficacy of EGFR-tyrosine kinase inhibitors (TKIs) for these cases is unclear. PATIENT CONCERNS AND DIAGNOSES: A 67-year-old man complained of paresis of the right lower extremity, dysarthria, and memory disturbance. Computed tomography and magnetic resonance imaging showed multiple brain tumors with brain edema and swelling of the left supraclavicular, mediastinal, and upper abdominal lymph nodes...
February 2018: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29438224/erlotinib-protects-lps-induced-acute-lung-injury-in-mice-by-inhibiting-egfr-tlr4-signaling-pathway
#8
Huan Tao, Na Li, Zhao Zhang, Honglan Mu, Chen Meng, Huimin Xia, Lisha Fu, Younian Xu, Shihai Zhang
Epidermal growth factor receptor (EGFR) has been reported to initiate the inflammatory response, but its activation in lipopolysaccharide (LPS)-induced murine model of acute lung injury (ALI) remains unclear. In this study, we investigated the role of EGFR in the LPS-induced murine model of ALI and explored whether its inhibitor erlotinib could affect the progression of lung injury. We first detected the phosphorylated EGFR (p-EGFR)/EGFR ratio at different time points after LPS stimulation, and then different concentrations of erlotinib were used to treat mice at 1 h before LPS stimulation and collected samples at the time point of the highest p-EGFR/EGFR ratio...
February 12, 2018: Shock
https://www.readbyqxmd.com/read/29434678/dynamic-changes-in-quality-of-life-after-three-first-line-therapies-for-egfr-mutation-positive-advanced-non-small-cell-lung-cancer
#9
Szu-Chun Yang, Chien-Chung Lin, Wu-Wei Lai, Sheng-Mao Chang, Jing-Shiang Hwang, Wu-Chou Su, Jung-Der Wang
Background: Three different tyrosine kinase inhibitors have been approved as first-line therapies for epidermal growth factor receptor (EGFR) mutation-positive advanced non-small-cell lung cancer with similar overall survival. This study determined dynamic changes in quality of life (QoL) for patients using these therapies after controlling for potential confounders. Methods: From 2011 to 2016, we prospectively assessed the utility values and QoL scores of patients using the EuroQol five-dimension and World Health Organization Quality-of-Life - Brief questionnaires...
2018: Therapeutic Advances in Medical Oncology
https://www.readbyqxmd.com/read/29430731/rapid-improvement-of-psoriasis-in-a-patient-with-lung-cancer-after-treatment-with-erlotinib
#10
L M Goepel, A Jacobi, M Augustin, M A Radtke
We report the case of a 48-year-old woman with a rapid improvement of her psoriasis after treatment with erlotinib.A metastasised non-small cell lung cancer (NSCLC) was diagnosed and the psoriasis treatment with ustekinumab was stopped which caused a flare up of her psoriasis. This article is protected by copyright. All rights reserved.
February 11, 2018: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/29423501/association-of-sulindac-and-erlotinib-vs-placebo-with-colorectal-neoplasia-in-familial-adenomatous-polyposis-secondary-analysis-of-a-randomized-clinical-trial
#11
N Jewel Samadder, Scott K Kuwada, Kenneth M Boucher, Kathryn Byrne, Priyanka Kanth, Wade Samowitz, David Jones, Sean V Tavtigian, Michelle Westover, Therese Berry, Kory Jasperson, Lisa Pappas, Laurel Smith, Danielle Sample, Randall W Burt, Deborah W Neklason
Importance: Patients with familial adenomatous polyposis (FAP) are at markedly increased risk for colorectal polyps and cancer. A combination of sulindac and erlotinib led to a 71% reduction in duodenal polyp burden in a phase 2 trial. Objective: To evaluate effect of sulindac and erlotinib on colorectal adenoma regression in patients with FAP. Design, Setting, and Participants: Prespecified secondary analysis for colorectal adenoma regression was carried out using data from a double-blind, randomized, placebo-controlled trial, enrolling 92 patients with FAP, conducted from July 2010 to June 2014 in Salt Lake City, Utah...
February 8, 2018: JAMA Oncology
https://www.readbyqxmd.com/read/29420339/probable-drug-drug-interaction-between-erlotinib-and-amiodarone-causes-severe-neurotoxicity-in-a-patient-with-advanced-lung-cancer
#12
Maria López Brunsó, Cristina Toro Blanch, Elia Sais Girona, Diana Roa García, Alejandro Hernández Martínez, Angel Izquierdo Font, Silvia Guerra Prió, Huber Gunter Mas Pueyo, Joaquim Bosch-Barrera
Drug-drug interactions (DDIs) are of great concern in the treatment of cancer, especially when target therapies, such as tyrosine kinase inhibitors, are being used. Here, we report a case of probable DDI between erlotinib and amiodarone leading to severe neurotoxicity. Amiodarone inhibits P-glycoprotein (P-gp), for which erlotinib is a substrate. P-gp is an important drug transporter that is involved in limiting the blood-brain barrier penetration of erlotinib. Clinicians should be aware of emerging data characterizing the effect of the P-gp transport system on drug exposure and its potential for DDI...
February 7, 2018: Anti-cancer Drugs
https://www.readbyqxmd.com/read/29410323/egfr-t790m-and-c797s-mutations-as-mechanisms-of-acquired-resistance-to-dacomitinib
#13
Yoshihisa Kobayashi, Toshio Fujino, Masaya Nishino, Takamasa Koga, Masato Chiba, Yuichi Sesumi, Shuta Ohara, Masaki Shimoji, Kenji Tomizawa, Toshiki Takemoto, Tetsuya Mitsudomi
INTRODUCTION: Dacomitinib is superior to gefitinib in terms of progression-free survival in patients with EGFR-mutant lung cancer in a recent ARCHER 1050 trial. However, despite a marked initial response, lung cancers eventually acquire resistance to these inhibitors. This study aimed to elucidate the mechanisms of acquired resistance to dacomitinib in vitro. METHODS: Dacomitinib-resistant clones were established by exposure to fixed concentrations of dacomitinib using N-ethyl-N-nitrosurea (ENU) mutagenesis or by chronic exposure to increasing concentrations of dacomitinib without ENU...
February 1, 2018: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/29404300/good-response-to-erlotinib-in-a-patient-after-progression-on-osimertinib-a-rare-case-of-spatiotemporal-t790m-heterogeneity-in-a-patient-with-epidermal-growth-factor-receptor-mutant-nonsmall-cell-lung-cancer
#14
Venkata Pradeep Babu Koyyala, Ullas Batra, Parveen Jain, Mansi Sharma, Pankaj Goyal, Kshitiz Domadia, Sneha Botra
No abstract text is available yet for this article.
October 2017: South Asian Journal of Cancer
https://www.readbyqxmd.com/read/29404164/treatment-after-first-generation-epidermal-growth-factor-receptor-tyrosine-kinase-inhibitor-resistance-in-non-small-cell-lung-cancer
#15
REVIEW
Seher Nazlı Kazaz, İlhan Öztop
Systemic treatment is the basic treatment approach to advanced-stage non-small-cell lung cancer (NSCLC), and chemotherapy and targeted treatments are commonly employed in these patients. Recently, positive results achieved with immunotherapy have led to a growing number of treatment options and prolonged survival time. Today, specific tyrosine kinase inhibitors (TKIs), such as erlotinib, gefitinib, and afatinib, which target the epidermal growth factor receptor (EGFR), and the TKI crizotinib, which targets anaplastic lymphoma kinase gene rearrangement, have become the standard treatment among targeted therapies for patients with sensitive molecular anomalies...
July 2017: Turkish Thoracic Journal
https://www.readbyqxmd.com/read/29399354/efficacy-of-osimertinib-in-a-patient-with-non-small-cell-lung-cancer-harboring-epithelial-growth-factor-receptor-exon-19-deletion-t790m-mutation-with-poor-performance-status
#16
Yoichi Nishii, Osamu Hataji, Kentaro Ito, Fumiaki Watanabe, Tetsu Kobayashi, Corina D'Alessandro-Gabazza, Masaaki Toda, Osamu Taguchi, Nobuyuki Yamamoto, Esteban C Gabazza
Osimertinib, a third-generation epithelial growth factor receptor (EGFR) tyrosine kinase inhibitor, has been demonstrated to be effective for treating patients with T790M-positive advanced non-small cell lung cancer (NSCLC) with a relatively good performance status (grade 0-1). Reports of therapeutic response to osimertinib in advanced NSCLC patients with poor performance status are infrequent. The present case report discusses a patient with advanced lung adenocarcinoma harboring EGFR exon 19 deletion and T790M mutation with central nervous system involvement and poor performance status...
February 2018: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/29398601/losmapimod-overcomes-gefitinib-resistance-in-non-small-cell-lung-cancer-by-preventing-tetraploidization
#17
Yiu To Yeung, Shuying Yin, Bingbing Lu, Suyu Fan, Ran Yang, Ruihua Bai, Chengjuan Zhang, Ann M Bode, Kangdong Liu, Zigang Dong
The epidermal growth factor receptor (EGFR) is known to play a critical role in non-small cell lung cancer (NSCLC). Constitutively active EGFR mutations, including in-frame deletion in exon 19 and L858R point mutation in exon 21, contribute about 90% of all EGFR-activating mutations in NSCLC. Although oral EGFR-tyrosine kinase inhibitors (TKIs), gefitinib and erlotinib, show dramatic clinical efficacy with significantly prolonged progression-free survival in patients harboring these EGFR-activating mutations, most of these patients will eventually develop acquired resistance...
February 1, 2018: EBioMedicine
https://www.readbyqxmd.com/read/29395121/prognostic-role-of-the-veristrat-test-in-first-line-patients-with-non-small-cell-lung-cancer-treated-with-platinum-based-chemotherapy
#18
Francesco Grossi, Carlo Genova, Erika Rijavec, Giulia Barletta, Federica Biello, Maria Giovanna Dal Bello, Krista Meyer, Joanna Roder, Heinrich Roder, Julia Grigorieva
OBJECTIVES: VeriStrat® is a blood-based test that utilizes matrix-assisted laser desorption/ionization time-of-flight (MALDI ToF) mass spectrometry to assign a binary classification of VeriStrat Good or VeriStrat Poor that is associated with treatment outcomes in cancer patients. A number of other studies have shown an association between VeriStrat status and clinical outcomes in second and subsequent lines of therapy. The prognostic properties of VeriStrat were demonstrated in the placebo arms of two randomized studies in non-small cell lung cancer (NSCLC): TOPICAL and BR...
December 13, 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/29391212/assessing-the-selective-therapeutic-efficacy-of-superparamagnetic-erlotinib-nanoparticles-in-lung-cancer-by-using-quantitative-magnetic-resonance-imaging-and-a-nuclear-factor-kappa-b-reporter-gene-system
#19
Fei-Ting Hsu, Hua-Shan Liu, Ahmed Atef Ahmed Ali, Ping-Huei Tsai, Yu-Chieh Kao, Chia-Feng Lu, Hsu-Shan Huang, Cheng-Yu Chen
Non-small-cell lung cancer (NSCLC) is the most common type of lung cancer. Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors are commonly used as the first-line treatment for advanced NSCLC; however, the efficacy of drug delivery remains unknown. Hence, we successfully developed erlotinib-conjugated iron oxide nanoparticles (FeDC-E NPs) as theranostic probe that can potentially provide a new avenue for monitoring drug delivering through noninvasive magnetic resonance imaging. MRI ΔR2* relaxivity measurements offer an opportunity to quantitatively evaluate the uptake of FeDC-E NPs at cellular and tumoral levels...
January 29, 2018: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/29388752/iron-oxide-nanoparticles-synergize-with-erlotinib-to-suppress-refractory-non-small-cell-lung-cancer-cell-proliferation-through-the-inhibition-of-erbb-pi3k-akt-and-pten-activation
#20
Meili Zhang, Buqing Sai, Pengfei Cao, Zheng Li, Liyang Zhang, Cijun Shuai, Xinye Wang, Jia Wang, Guiyuan Li, Juanjuan Xiang, Jingqun Tang
Non-small cell lung cancer (NSCLC) accounts for 85% of lung cancer cases. EGFR tyrosine kinase inhibitors (EGFR-TKIs) such as erlotinib and gefitinib, are currently approved for the management of NSCLC. However, primary and acquired resistances to EGFR-TKIs are the major obstacles in the treatment of NSCLC. These resistances have been associated with the development of secondary mutations in EGFR or continued oncogenic signaling despite TKI treatment. In this study, NSCLC cells with wild-type EGFR, A549, H460, H358, H157 which do not respond to EGFR-TKIs, were used...
April 2017: Journal of Biomedical Nanotechnology
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