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https://www.readbyqxmd.com/read/28742280/clinical-outcomes-in-patients-with-advanced-egfr-mutated-non-small-cell-lung-cancer-in-south-western-sydney-local-health-district
#1
P N Ding, T L Roberts, W Chua, T M Becker, J Descallar, P Y Yip, V J Bray
AIMS: We aim to describe clinical characteristics, treatment patterns and factors influencing outcomes in patients with EGFR-mutated non-small cell lung cancer (NSCLC) in SWSLHD. METHODS: Retrospective review of patients with EGFR-mutated NSCLC diagnosed between January 2010 and June 2016. RESULTS: A total of 85 EGFR-mutated NSCLC patients were identified; 80 (94%) received first line treatment with EGFR-TKI. The median follow-up was 10.7 months with a median duration of treatment of 9 months...
July 25, 2017: Internal Medicine Journal
https://www.readbyqxmd.com/read/28739703/cerebrospinal-fluid-penetration-rate-and-efficacy-of-afatinib-in-patients-with-egfr-mutation-positive-non-small-cell-lung-cancer-with-leptomeningeal-carcinomatosis-a-multicenter-prospective-study
#2
Akihiro Tamiya, Motohiro Tamiya, Takashi Nishihara, Takayuki Shiroyama, Keiko Nakao, Taisuke Tsuji, Naoko Takeuchi, Shun-Ichi Isa, Naoki Omachi, Norio Okamoto, Hidekazu Suzuki, Kyoichi Okishio, Ayano Iwazaki, Kimie Imai, Tomonori Hirashima, Shinji Atagi
BACKGROUND: Afatinib is an effective first-line treatment for epidermal growth factor receptor (EGFR) mutation-positive advanced non-small cell lung cancer (NSCLC). However, few reports have addressed the influence of cerebrospinal fluid (CSF) penetration rate on the efficacy of afatinib in patients with central nervous system metastases. Therefore, we conducted a prospective multicenter trial to evaluate the CSF penetration rate and efficacy of afatinib in patients with EGFR mutation-positive NSCLC with leptomeningeal carcinomatosis...
August 2017: Anticancer Research
https://www.readbyqxmd.com/read/28735814/tyrosine-kinase-inhibitors-as-modulators-of-trastuzumab-mediated-antibody-dependent-cell-mediated-cytotoxicity-in-breast-cancer-cell-lines
#3
Denis M Collins, Kathy Gately, Clare Hughes, Connla Edwards, Anthony Davies, Stephen F Madden, Kenneth J O'Byrne, Norma O'Donovan, John Crown
BACKGROUND: Trastuzumab is an anti-HER2 monoclonal antibody (mAb) therapy capable of antibody-dependent cell-mediated cytotoxicity (ADCC) and used in the treatment of HER2+ breast cancer. Through interactions with FcƴR+ immune cell subsets, trastuzumab functions as a passive immunotherapy. The EGFR/HER2-targeting tyrosine kinase inhibitor (TKI) lapatinib and the next generation TKIs afatinib and neratinib, can alter HER2 levels, potentially modulating the ADCC response to trastuzumab...
July 15, 2017: Cellular Immunology
https://www.readbyqxmd.com/read/28731495/significance-of-neutrophil-to-lymphocyte-ratio-in-western-advanced-egfr-mutated-non-small-cell-lung-cancer-receiving-a-targeted-therapy
#4
Fausto Meriggi, Claudio Codignola, Giordano D Beretta, Giovanni L Ceresoli, Alberto Caprioli, Mario Scartozzi, Anna P Fraccon, Tiziana Prochilo, Chiara Ogliosi, Alberto Zaniboni
PURPOSE: Lung cancer is one of the leading causes of cancer-related death worldwide and, although targeted therapy with tyrosine kinase inhibitors has dramatically improved the rates of response and survival in advanced EGFR-mutated adenocarcinoma, the overall outcome remains unsatisfactory. Therefore, new prognostic factors, preferably simple, inexpensive, and easy to reproduce on a large scale, are needed. We performed a retrospective analysis of our database including 63 western Caucasian patients with advanced EGFR-mutated lung adenocarcinoma and receiving gefitinib, erlotinib, or afatinib as first- or second-line therapy...
July 14, 2017: Tumori
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
#5
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/28729180/symptom-and-quality-of-life-improvement-in-lux-lung-8-an-open-label-phase-iii-study-of-second-line-afatinib-versus-erlotinib-in-patients-with-advanced-squamous-cell-carcinoma-of-the-lung-after-first-line-platinum-based-chemotherapy
#6
Enriqueta Felip, Vera Hirsh, Sanjay Popat, Manuel Cobo, Andrea Fülöp, Charles Dayen, José M Trigo, Richard Gregg, Cornelius F Waller, Jean-Charles Soria, Glenwood D Goss, James Gordon, Bushi Wang, Michael Palmer, Eva Ehrnrooth, Shirish M Gadgeel
INTRODUCTION: In the phase III LUX-Lung 8 trial, afatinib significantly improved progression-free survival (PFS) and overall survival (OS) versus erlotinib in patients with squamous cell carcinoma (SCC) of the lung progressing during or after platinum-based chemotherapy. Patient-reported outcomes (PROs) and health-related quality of life (QoL) in these patients are presented. PATIENTS AND METHODS: Patients (n = 795) were randomized 1:1 to oral afatinib (40 mg/d) or erlotinib (150 mg/d)...
June 23, 2017: Clinical Lung Cancer
https://www.readbyqxmd.com/read/28718011/case-series-on-the-association-between-blood-levels-and-side-effects-of-afatinib-maleate
#7
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/28708233/treatment-in-egfr-mutated-non-small-cell-lung-cancer-how-to-block-the-receptor-and-overcome-resistance-mechanisms
#8
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/28702338/-liquid-elbows-due-to-afatinib-administration
#9
Paul Zarogoulidis, Panos Chinelis, Anastasia Athanasiadou, Konstantinos Porpodis, Anastasios Kallianos, Aggeliki Rapti, Georgia Trakada, Lemonia Velentza, Haidong Huang, Theodora Tsiouda, Wolfgang Hohenforst-Schmidt
Non-small cell lung cancer adenocarcinoma in the past decade has targeted therapies as the cornerstone for therapy. In specific patients with epidermal growth factor receptor mutation have three different therapy approaches with the tyrosine kinase inhibitors: erlotinib, gefitinib and afatinib. Nowadays we can use tyrosine kinase inhibitors as second line treatment for squamous cell carcinoma. We present a case with a patient with squamous cell carcinoma receiving afatinib tyrosine kinase inhibitor who presented elbow bursitis or olecranon bursitis in both elbows...
2017: Respiratory Medicine Case Reports
https://www.readbyqxmd.com/read/28684658/the-efficacy-of-40-mg-versus-dose-de-escalation-to-less-than-40-mg-of-afatinib-giotrif-as-the-first-line-therapy-for-patients-with-primary-lung-adenocarcinoma-harboring-favorable-epidermal-growth-factor-mutations
#10
Chien-Ying Liu, Cheng-Ta Yang, Chih-Liang Wang, Shih-Hong Li, Ping-Chih Hsu, Chih-Hung Chen, Ting-Yu Lin, Chih-Hsi Kuo, Yueh-Fu Fang, How-Wen Ko, Chih-Teng Yu, Tai-Yun Yang
The choice of a first-line therapy for lung cancer is a crucial decision that can impact the survival as well as the quality of life of a patient. Inhibitors of epidermal growth factor receptor (EGFR) such as afatinib, erlotinib, and gefitinib have previously been used to treat non-small cell lung cancer harboring favorable EGFR mutations. Although afatinib has greater efficacy than other EGFR inhibitors, adverse events related to its use can result in the discontinuation of the therapy. In this study, we compared the therapeutic efficacy in lung cancer patients of a regimen of 40 mg/day of afatinib with that of a lower dose regimen of <40 mg/day resulting either from a lower starting dose of 30 mg/day or dose adjustment...
June 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28680960/efficacy-and-safety-results-of-the-afatinib-expanded-access-program
#11
Edward S Kim, Balazs Halmos, Ingrid F Kohut, Taral Patel, Regan D Rostorfer, Alexander I Spira, Agnieszka Cseh, John McKay, Gudrun Wallenstein, Kathryn F Mileham
INTRODUCTION: Afatinib is an oral, irreversible ErbB family blocker approved for first-line treatment of metastatic epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC). The expanded access program (EAP) allowed early access to afatinib and provided additional data on its safety, tolerability, and efficacy. METHODS: The afatinib EAP was an open-label, multicenter, single-arm program in the United States that treated and followed patients with locally advanced or metastatic NSCLC harboring EGFR mutations...
2017: Oncology and Therapy
https://www.readbyqxmd.com/read/28676644/blocking-autophagy-improves-the-anti-tumor-activity-of-afatinib-in-lung-adenocarcinoma-with-activating-egfr-mutations-in-vitro-and-in-vivo
#12
Xiangxiang Hu, Si Shi, Huan Wang, Xiaochen Yu, Qian Wang, Shanshan Jiang, Dianwen Ju, Li Ye, Meiqing Feng
Afatinib, a second-generation tyrosine kinase inhibitor (TKI), has been approved for the treatment of advanced EGFR-mutant non-small cell lung cancer (NSCLC). However, afatinib's clinical application is still hampered by acquired resistance. Recently, autophagy is considered as an important mechanism of resistance to TKI. Herein, we investigated the autophagy induction as well as its influence on anti-lung adenocarcinoma activity of afatinib in two activating EGFR-mutants H1975 and H1650 cells. First, Growth inhibition and caspase-dependent apoptosis were observed in afatinib-treated H1975 and H1650 cells...
July 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28676222/optimal-management-of-egfr-mutant-non-small-cell-lung-cancer-with-disease-progression-on-first-line-tyrosine-kinase-inhibitor-therapy
#13
REVIEW
Bin-Chi Liao, Chia-Chi Lin, Jih-Hsiang Lee, James Chih-Hsin Yang
The first-generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), gefitinib and erlotinib, and the second-generation EGFR-TKI, afatinib, have all been approved as standard first-line treatments for advanced EGFR-mutant non-small cell lung cancer (NSCLC) based on superior progression-free survival results compared to platinum doublet chemotherapy regimens. Acquired resistance to an EGFR-TKI inevitably develops after a period of effective drug treatment. After tumor progression, many combination therapy regimens that include an EGFR-TKI, or EGFR-TKI monotherapy, have been tested in prospective trials with the aim of extending survival...
August 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/28676220/comparing-the-effects-of-afatinib-with-gefitinib-or-erlotinib-in-patients-with-advanced-stage-lung-adenocarcinoma-harboring-non-classical-epidermal-growth-factor-receptor-mutations
#14
Yi-Cheng Shen, Guan-Chin Tseng, Chih-Yeh Tu, Wei-Chun Chen, Wei-Chih Liao, Wei-Cheng Chen, Chia-Hsiang Li, Hung-Jen Chen, Te-Chun Hsia
OBJECTIVE: Approximately 10%-15% patients with epidermal growth factor receptor (EGFR) mutations harbor non-classical mutations. However, the effects of EGFR-tyrosine kinases (TKIs), particularly second-generation EGFR-TKI (afatinib) compared to first-generation EGFR-TKIs (gefitinib/erlotinib), in patients with non-classical EGFR mutations remain unknown. METHODS: We conducted this retrospective study at the China Medical University Hospital (Taichung, Taiwan) from June 2011 to July 2016...
August 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/28675660/meta-analysis-of-first-line-therapies-with-maintenance-regimens-for-advanced-non-small-cell-lung-cancer-nsclc-in-molecularly-and-clinically-selected-populations
#15
Pui San Tan, Marcel Bilger, Gilberto de Lima Lopes, Sanchalika Acharyya, Benjamin Haaland
Evidence has suggested survival benefits of maintenance for advanced NSCLC patients not progressing after first-line chemotherapy. Additionally, particular first-line targeted therapies have shown survival improvements in selected populations. Optimal first-line and maintenance therapies remain unclear. Here, currently available evidence was synthesized to elucidate optimal first-line and maintenance therapy within patient groups. Literature was searched for randomized trials evaluating first-line and maintenance regimens in advanced NSCLC patients...
July 3, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28668844/the-effect-of-afatinib-treatment-in-non-small-cell-lung-cancer-cells
#16
Joanna Pancewicz-Wojtkiewicz, Pawel Leszek Bernatowicz
BACKGROUND: Non-small cell lung cancer (NSCLC) is a very aggressive and histologically heterogeneous type of lung cancer. The main problem in the treatment of NSCLC is chemoresistance and metastasis. Compared to other malignant tumors, many molecular mechanisms are dysfunctional in NSCLC. Epidermal growth factor receptor (EGFR) is one of the most frequently mutated genes in NSCLC. MATERIALS AND METHODS: We investigated the effect of afatinib the against A549 NSCLC cell line, because it is active against mutated EGFR...
July 2017: Anticancer Research
https://www.readbyqxmd.com/read/28657354/update-on-afatinib-based-combination-regimens-for-the-treatment-of-egfr-mutation-positive-non-small-cell-lung-cancer
#17
Jaafar Bennouna
No abstract text is available yet for this article.
June 28, 2017: Future Oncology
https://www.readbyqxmd.com/read/28656962/negative-regulation-of-egfr-signalling-by-the-human-folliculin-tumour-suppressor-protein
#18
Laura A Laviolette, Julien Mermoud, Isabel A Calvo, Nicholas Olson, Myriam Boukhali, Ortrud K Steinlein, Elisabeth Roider, Elke C Sattler, Dachuan Huang, Bin Tean Teh, Mo Motamedi, Wilhelm Haas, Othon Iliopoulos
Germline mutations in the Folliculin (FLCN) tumour suppressor gene result in fibrofolliculomas, lung cysts and renal cancers, but the precise mechanisms of tumour suppression by FLCN remain elusive. Here we identify Rab7A, a small GTPase important for endocytic trafficking, as a novel FLCN interacting protein and demonstrate that FLCN acts as a Rab7A GTPase-activating protein. FLCN(-/-) cells display slower trafficking of epidermal growth factor receptors (EGFR) from early to late endosomes and enhanced activation of EGFR signalling upon ligand stimulation...
June 28, 2017: Nature Communications
https://www.readbyqxmd.com/read/28656237/matrine-increases-the-inhibitory-effects-of-afatinib-on-h1975-cells-via-the-il%C3%A2-6-jak1-stat3-signaling-pathway
#19
Shui-Fang Chen, Ze-Ying Zhang, Jian-Li Zhang
Resistance to epidermal growth factor receptor (EGFR) inhibitors is of primary concern in the treatment of non‑small‑cell lung cancer (NSCLC) with EGFR mutations. To investigate the effects of matrine on H1975 cells and to examine a novel, potential treatment option for NSCLC, the present study measured cell viability, apoptotic rate, interleukin 6 (IL‑6) expression and activation of the janus kinase (JAK) 1/signal transducer and activator of transcription (STAT)3 signaling pathway in cells treated with or without matrine, in the presence or absence of afatinib...
September 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28656214/her2-regulates-cancer-stem-like-cell-phenotype-in-alk-translocated-nsclc
#20
Tiia Honkanen, Emmi Wilenius, Peppi Koivunen, Jussi P Koivunen
We have previously shown that cancer stem-like cells (CSLCs) can mediate therapy resistance in ALK translocated lung cancers. HER2 has been linked to CSLCs in breast cancers and, therefore, we wanted to assess whether HER2 has a role in CSLCs in ALK translocated cancers. ALK translocated cell lines, H3122 and H2228, with variable sensitivity to ALK inhibition were used in the study. HER2 overexpression or knockdown was induced by retro- or lentiviral infections and cells were treated with pharmacological agents targeting HER2 and ALK signaling...
June 21, 2017: International Journal of Oncology
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