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https://www.readbyqxmd.com/read/28089942/targeting-egfr-t790m-mutation-in-nsclc-from-biology-to-evaluation-and-treatment
#1
Antonio Passaro, Elena Guerini-Rocco, Alessia Pochesci, Davide Vacirca, Gianluca Spitaleri, Chiara Matilde Catania, Alessandra Rappa, Massimo Barberis, Filippo de Marinis
The identification of EGFR mutations and their respectively tyrosine kinase inhibitors (TKIs), changed dramatically treatment and survival of patients with EGFR-positive lung cancer. Nowadays, different EGFR TKIs as afatinib, erlotinib and gefitinib are approved worldwide for the treatment of NSCLC harbouring EGFR mutations, in particular exon 19 deletions or exon 21 (Leu858Arg) substitution EGFR mutations. In first-line setting, when comparing with platinum-based chemotherapy, these target drugs improves progression-free survival, response rate and quality of life...
January 12, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28088511/brief-report-egfr-l858m-l861q-cis-mutations-confer-selective-sensitivity-to-afatinib
#2
Jamie A Saxon, Lynette M Sholl, Pasi A Jänne
INTRODUCTION: Tyrosine kinase inhibitors (TKIs) have been developed to treat patients with epidermal growth factor receptor (EGFR)-mutant lung cancers. However, the therapeutic efficacy of TKIs in patients with uncommon EGFR mutations remains unclear. METHODS: Next-generation sequencing was performed on a patient's lung adenocarcinoma tumor sample, revealing rare combined in cis (on the same allele) EGFR mutations. Stable Ba/F3 and NIH-3T3 cell lines harboring the mutations were established to investigate the effect of first, second, and third generation EGFR TKIs on cell proliferation by MTS assay and EGFR phosphorylation by Western blotting...
January 11, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28087951/a-phase-ii-study-of-concurrent-chemoradiotherapy-and-erlotinib-for-inoperable-esophageal-squamous-cell-carcinoma
#3
Chuanhua Zhao, Li Lin, Jianzhi Liu, Rongrui Liu, Yuling Chen, Feijiao Ge, Ru Jia, Yang Jin, Yan Wang, Jianming Xu
Cisplatin-based concurrent chemoradiotherapy for patients with unresectable, locally advanced esophageal squamous cell carcinoma (ESCC) is associated with significant toxicities that are often intolerable. Prognosis for this subgroup of patients remains poor, and new therapeutic approaches are urgently needed. We investigated the efficacy and safety of paclitaxel combined with erlotinib and concurrent radiotherapy in patients with inoperable ESCC. Erlotinib (150 mg) was administered daily for 60 days beginning at the start of radiotherapy, and paclitaxel (45 mg/m²) was administered weekly along with intensity modulated conformal radiotherapy (60 Gy in 30 fractions)...
August 30, 2016: Oncotarget
https://www.readbyqxmd.com/read/28075527/recent-development-of-the-second-and-third-generation-irreversible-egfr-inhibitors
#4
REVIEW
Weiwei Han, Yongli Du
Recent reports suggested that essential directions for new lung cancer, breast carcinoma therapies, as well as the roomier realm of targeted cancer therapies were provided through targeting the epidermal growth factor receptor (EGFR). Patients who carrying non-small cell lung carcinoma (NSCLC) with activating mutations in EGFR initially respond well to the EGFR inhibitors erlotinib and gefitinib, which were located the active site of the EGFR kinase and designed to act as competitive inhibitors of combining with the ATP...
January 11, 2017: Chemistry & Biodiversity
https://www.readbyqxmd.com/read/28073786/phase-1-study-of-twice-weekly-pulse-dose-and-daily-low-dose-erlotinib-as-initial-treatment-for-patients-with-egfr-mutant-lung-cancers
#5
H A Yu, C Sima, D Feldman, L L Liu, B Vaitheesvaran, J Cross, C M Rudin, M G Kris, W Pao, F Michor, G J Riely
BACKGROUND: Patients with EGFR-mutant lung cancers treated with EGFR tyrosine kinase inhibitors (TKIs) develop clinical resistance, most commonly with acquisition of EGFR T790M. Evolutionary modeling suggests that a schedule of twice weekly pulse and daily low-dose erlotinib may delay emergence of EGFR T790M. Pulse dose erlotinib has superior central nervous system (CNS) penetration and may result in superior CNS disease control. METHODS: We evaluated toxicity, pharmacokinetics, and efficacy of twice weekly pulse and daily low-dose erlotinib...
October 25, 2016: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28064206/retrospective-analysis-of-survival-in-patients-with-leptomeningeal-carcinomatosis-from-lung-adenocarcinoma-treated-with-erlotinib-and-gefitinib
#6
Jumpei Kashima, Yusuke Okuma, Maki Miwa, Yukio Hosomi
BACKGROUND: Leptomeningeal carcinomatosis is a relatively rare metastatic form of non-small cell lung cancer, which can impact prognosis. There is an increasing need for selecting suitable epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors among those currently included in standard care for EGFR mutation-positive patients. We compared the efficacy of gefitinib and erlotinib in survival of patients with leptomeningeal carcinomatosis. PATIENTS AND METHODS: The medical records of 269 patients who received tyrosine kinase inhibitors at a single center were retrospectively reviewed...
January 6, 2017: Japanese Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28061541/a-prospective-multicenter-phase-ii-trial-of-low-dose-erlotinib-as-maintenance-treatment-after-platinum-doublet-chemotherapy-for-advanced-non-small-cell-lung-cancer-harboring-egfr-mutation
#7
Satoshi Hirano, Go Naka, Yuichiro Takeda, Motoyasu Iikura, Noriko Hayama, Asako Yanagisawa, Hiroyuki Amano, Makoto Nakamura, Sukeyuki Nakamura, Hiroshi Tabeta, Haruhito Sugiyama
BACKGROUND: Maintenance therapy with full-dose erlotinib for patients with advanced non-small cell lung cancer (NSCLC) has demonstrated a significant overall survival (OS) benefit. However, 150 mg/day of erlotinib seems too toxic as maintenance therapy. This study aimed to evaluate the efficacy and safety of low-dose erlotinib (25 mg/day) as maintenance treatment after platinum doublet chemotherapy in NSCLC harboring epidermal growth factor receptor (EGFR) mutation. METHODS: Activated EGFR-mutation-positive NSCLC patients who did not progress after first-line platinum-doublet chemotherapy, ≥20 and ≤85 years old, with performance status (PS) 0-3 were included in this study...
December 2016: Chinese Clinical Oncology
https://www.readbyqxmd.com/read/28061471/transformation-to-small-cell-carcinoma-as-an-acquired-resistance-mechanism-to-azd9291-a-case-report
#8
Lin Li, Hui Wang, Chao Li, Zheng Wang, Ping Zhang, Xu Yan
AZD9291, a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), benefits patients with T790M mutant non-small-cell lung cancer who fail treatment with first-generation EGFR TKIs. Acquisition of resistance to AZD9291 occurs inevitable and mechanisms need to be explored. We reported an advanced lung adenocarcinoma female with EGFR exon19 deletion treated on AZD9291 after failure of erlotinib and chemotherapy. Disease progressed again after 6 months' treatment of AZD9291 with hepatic metastasis...
January 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28059038/toxicities-of-receptor-tyrosine-kinase-inhibitors-in-cancer-pharmacotherapy-management-with-clinical-pharmacology
#9
Ken-Ichi Fujita, Hiroo Ishida, Yutaro Kubota, Yasutsuna Sasaki
A number of molecularly targeted anticancer drugs that efficiently inhibit receptor tyrosine kinases, so-called receptor tyrosine kinase inhibitors (TKIs), have been developed. Although these receptor TKIs are generally well tolerated, unexpected toxicities sometimes occur in various organs. TKI-induced adverse events not only lower the quality of life of cancer patients but also reduce dose intensity, and sometimes result in treatment discontinuation. To reduce adverse drug events and increase treatment efficacy, oncologists and clinical pharmacologists have made efforts to establish strategies to treat patients via optimal selection and dosing of TKIs...
January 5, 2017: Current Drug Metabolism
https://www.readbyqxmd.com/read/28057415/comprehensive-genomic-analysis-of-metastatic-mucinous-urethral-adenocarcinoma-guides-precision-oncology-treatment-targetable-egfr-amplification-leading-to-successful-treatment-with-erlotinib
#10
Alan H Bryce, Mitesh J Borad, Jan B Egan, Rachel M Condjella, Winnie S Liang, Rafael Fonseca, Ann E McCullough, Katherine S Hunt, Nicole R Ritacca, Michael T Barrett, Maitray D Patel, Scott W Young, Alvin C Silva, Thai H Ho, Thorvardur R Halfdanarson, Melissa L Stanton, John Cheville, Scott Swanson, Daniel E Schneider, Robert R McWilliams, Angela Baker, Jessica Aldrich, Ahmet Kurdoglu, Tyler Izatt, Alexis Christoforides, Irene Cherni, Sara Nasser, Rebecca Reiman, Lori Cuyugan, Jacquelyn McDonald, Jonathan Adkins, Stephen D Mastrian, Daniel D Von Hoff, David W Craig, A Keith Stewart, John D Carpten
No abstract text is available yet for this article.
December 1, 2016: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/28056412/toxicity-of-concurrent-stereotactic-radiotherapy-and-targeted-therapy-or-immunotherapy-a-systematic-review
#11
REVIEW
Stephanie G C Kroeze, Corinna Fritz, Morten Hoyer, Simon S Lo, Umberto Ricardi, Arjun Sahgal, Rolf Stahel, Roger Stupp, Matthias Guckenberger
BACKGROUND AND PURPOSE: Both stereotactic radiotherapy (SRT) and immune- or targeted therapy play an increasingly important role in personalized treatment of metastatic disease. Concurrent application of both therapies is rapidly expanding in daily clinical practice. In this systematic review we summarize severe toxicity observed after concurrent treatment. MATERIAL AND METHODS: PubMed and EMBASE databases were searched for English literature published up to April 2016 using keywords "radiosurgery", "local ablative therapy", "gamma knife" and "stereotactic", combined with "bevacizumab", "cetuximab", "crizotinib", "erlotinib", "gefitinib", "ipilimumab", "lapatinib", "sorafenib", "sunitinib", "trastuzumab", "vemurafenib", "PLX4032", "panitumumab", "nivolumab", "pembrolizumab", "alectinib", "ceritinib", "dabrafenib", "trametinib", "BRAF", "TKI", "MEK", "PD1", "EGFR", "CTLA-4" or "ALK"...
December 19, 2016: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28052650/patient-derived-xenograft-models-of-epithelial-ovarian-cancer-for-preclinical-studies
#12
Eun Jin Heo, Young Jae Cho, William Chi Cho, Ji Eun Hong, Hye-Kyung Jeon, Doo-Yi Oh, Yoon-La Choi, Sang Yong Song, Jung-Joo Choi, Duk-Soo Bae, Yoo-Young Lee, Chel Hun Choi, Tae-Joong Kim, Woong-Yang Park, Byoung-Gie Kim, Jeong-Won Lee
Purpose: Patient-derived tumor xenografts (PDXs) can provide more reliable information about tumor biology than cell line models. We developed PDXs for epithelial ovarian cancer (EOC) that have histopathologic and genetic similarities to the primary patient tissues and evaluated their potential for use as a platform for translational EOC research. Materials and Methods: We successfully established PDXs by subrenal capsule implantation of primary EOC tissues into female BALB/C-nude mice...
January 4, 2017: Cancer Research and Treatment: Official Journal of Korean Cancer Association
https://www.readbyqxmd.com/read/28045621/antineoplastic-treatment-of-advanced-stage-non-small-cell-lung-cancer-treatment-survival-and-spending-2000-to-2011
#13
Cathy J Bradley, K Robin Yabroff, Angela B Mariotto, Christopher Zeruto, Quyen Tran, Joan L Warren
Purpose Multiple agents for advanced non-small-cell lung cancer (NSCLC) have been approved in the past decade, but little is known about their use and associated spending and survival. Methods We used SEER-Medicare data for elderly patients with a new diagnosis of advanced-stage NSCLC and were treated with antineoplastic agents between 2000 and 2011 (N = 22,163). We estimated the adjusted percentage of patients who received each agent, days while on treatment, survival, and spending in the 12 months after diagnosis...
January 3, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28045335/phase-ii-trial-of-capecitabine-plus-erlotinib-versus-capecitabine-alone-in-patients-with-advanced-colorectal-cancer
#14
Mark D Vincent, Daniel Breadner, Denis Soulieres, Ian G Kerr, Michael Sanatani, Walter Kocha, Peter Klimo, Mary J MacKenzie, Anne O'Connell, Frances Whiston, Anne S Malpage, Larry Stitt, Stephen A Welch
: Aim & methods: Capecitabine monotherapy as palliation for advanced colorectal cancer (CRC) is generally well tolerated. Adding erlotinib, an EGFR-tyrosine kinase inhibitor, might improve efficacy versus capecitabine alone. 82 patients received capecitabine alone (Arm 1) or capecitabine with erlotinib (Arm 2). RESULTS: Median time-to-progression (TTP) in Arm 1 was 7.9 months versus 9.2 in Arm 2. In KRAS-wild type (WT) patients TTP was 8.4 and 11.7 months in Arms 1 and 2, respectively...
January 3, 2017: Future Oncology
https://www.readbyqxmd.com/read/28043153/outcome-of-egfr-inhibitors-treatment-in-advanced-nsclc-patients-not-enrolled-in-clinical-trials
#15
M Mencoboni, R A Filiberti, P Taveggia, A Bruzzone, A Garuti, L Del Corso, E Ginocchio, A Brianti, C Simonassi, P Zucali
Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have become a treatment after first-line chemotherapy in patients with advanced NSCLC. We assessed the predictive and prognostic role of EGFR and Kras mutations in NSCLC patients treated with TKIs after progression, not included in clinical trials. Gefitinib 250 mg or Erlotinib 150 mg per os were administered to 70 patients. Radiological assessment was performed every six weeks. EGFR and Kras mutations were found in 21.4% and 24.3% of patients, respectively...
January 3, 2017: Neoplasma
https://www.readbyqxmd.com/read/28038980/epidermal-growth-factor-receptor-mutational-testing-and-erlotinib-treatment-among-veterans-diagnosed-with-lung-cancer-in-the-united-states-department-of-veterans-affairs
#16
Julie A Lynch, Brygida Berse, Danielle Chun, Donna Rivera, Kelly K Filipski, Scott Kulich, Benjamin Viernes, Scott L DuVall, Michael J Kelley
INTRODUCTION: We examined mutational testing of the epidermal growth factor gene (EGFR) and erlotinib treatment among veterans diagnosed with non-small-cell lung cancer in the United States Department of Veterans Affairs (VA). Our objectives were to identify the prevalence of clinically actionable EGFR mutations, to determine whether testing and treatment were guideline concordant, to evaluate the impact of testing and treatment on survival, and to estimate the rate of testing. PATIENTS AND METHODS: Test results were linked to electronic health records from VA Corporate Data Warehouse and the VA Central Cancer Registry...
December 7, 2016: Clinical Lung Cancer
https://www.readbyqxmd.com/read/28038979/preclinical-evaluation-of-met-inhibitor-inc-280-with-or-without-the-epidermal-growth-factor-receptor-inhibitor-erlotinib-in-non-small-cell-lung-cancer
#17
Matthew S Lara, William S Holland, Danielle Chinn, Rebekah A Burich, Primo N Lara, David R Gandara, Karen Kelly, Philip C Mack
BACKGROUND: Although the epidermal growth factor receptor (EGFR) inhibitor erlotinib is initially effective in non-small-cell lung cancer (NSCLC) patients with tumors harboring activating mutations of EGFR, most subsequently develop acquired resistance. One recognized resistance mechanism occurs through activation of bypass signaling via the hepatocyte growth factor (HGF)-MET pathway. INC-280 is a small molecule kinase inhibitor of MET. We sought to demonstrate the activity of INC-280 on select NSCLC cell lines both as a single agent and in combination with erlotinib using exogenous HGF to simulate MET up-regulation...
November 21, 2016: Clinical Lung Cancer
https://www.readbyqxmd.com/read/28031840/concomitant-t790m-mutation-and-small-cell-lung-cancer-transformation-after-acquired-resistance-to-epidermal-growth-factor-receptor-tyrosine-kinase-inhibitor
#18
Kohei Fujita, Young Hak Kim, Akihiko Yoshizawa, Tadashi Mio, Michiaki Mishima
A 70-year-old man was admitted to our hospital with an abnormal chest X-ray shadow. Bronchoscopy revealed an adenocarcinoma tumour with an epidermal growth factor receptor (EGFR) exon 19 deletion. Positron emission tomography-computed tomography scanning and magnetic resonance imaging showed advanced stage IV lung cancer. He was treated with erlotinib as a first-line drug, which maintained a clinical response for 16 months. After disease progression, a re-biopsy was done from the tumour in the right lower lobe...
January 2017: Respirology Case Reports
https://www.readbyqxmd.com/read/28031719/potential-role-of-immunotherapy-in-advanced-non-small-cell-lung-cancer
#19
REVIEW
Ramon Andrade de Mello, Ana Flávia Veloso, Paulo Esrom Catarina, Sara Nadine, Georgios Antoniou
Immuno checkpoint inhibitors have ushered in a new era with respect to the treatment of advanced non-small-cell lung cancer. Many patients are not suitable for treatment with epidermal growth factor receptor tyrosine kinase inhibitors (eg, gefitinib, erlotinib, and afatinib) or with anaplastic lymphoma kinase inhibitors (eg, crizotinib and ceritinib). As a result, anti-PD-1/PD-L1 and CTLA-4 inhibitors may play a novel role in the improvement of outcomes in a metastatic setting. The regulation of immune surveillance, immunoediting, and immunoescape mechanisms may play an interesting role in this regard either alone or in combination with current drugs...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28030863/real-world-clinical-practice-of-intensified-chemotherapies-for-metastatic-pancreatic-cancer-results-from-a-pan-european-questionnaire-study
#20
Nha Le, Alessio Vinci, Marvin Schober, Sebastian Krug, Muhammad A Javed, Thomas Kohlmann, Malin Sund, Albrecht Neesse, Georg Beyer
INTRODUCTION: Recently, FOLFIRINOX and gemcitabine + nab-paclitaxel have been introduced as a novel intensified chemotherapy regimen for patients with metastasized pancreatic cancer. This study aims to analyze the real-world clinical practice with FOLFIRINOX and gemcitabine + nab-paclitaxel across Europe. METHODS: Invitations to participate in an anonymous web-based questionnaire were sent via e-mail to 5,420 doctors in 19 European countries through the network of national gastroenterological, oncological, surgical and pancreatic societies as well as the European Pancreatic Club...
December 29, 2016: Digestion
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