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https://www.readbyqxmd.com/read/28934120/angiogenesis-inhibitors-in-nsclc
#1
REVIEW
Anna Manzo, Agnese Montanino, Guido Carillio, Raffaele Costanzo, Claudia Sandomenico, Nicola Normanno, Maria Carmela Piccirillo, Gennaro Daniele, Francesco Perrone, Gaetano Rocco, Alessandro Morabito
Angiogenesis is a complex biological process that plays a relevant role in sustaining the microenvironment, growth, and metastatic potential of several tumors, including non-small cell lung cancer (NSCLC). Bevacizumab was the first angiogenesis inhibitor approved for the treatment of patients with advanced NSCLC in combination with chemotherapy; however, it was limited to patients with non-squamous histology and first-line setting. Approval was based on the results of two phase III trials (ECOG4599 and AVAIL) that demonstrated an improvement of about two months in progression-free survival (PFS) in both trials, and in the ECOG4599 trial, an improvement in overall survival (OS) also...
September 21, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28933616/are-newly-launched-pharmacotherapies-efficacious-in-treating-idiopathic-pulmonary-fibrosis-or-is-there-still-more-work-to-be-done
#2
Riccardo Inchingolo, Carola Condoluci, Andrea Smargiassi, Annelisa Mastrobattista, Cristina Boccabella, Alessia Comes, Nicoletta Golfi, Luca Richeldi
Idiopathic pulmonary fibrosis (IPF) is a challenging and multifactorial disease that has been thought for some time to lack effective treatments. The approval of two drugs, nintedanib and pirfenidone, has heralded a new era in its management. Areas covered: Currently, there is a growing interest on therapeutic strategies. Many studies have been designed and performed, although few of them turned out to be successful. Nowadays, nintedanib and pirfenidone are considered disease modifying drugs, recommended treatments by current evidence-based guidelines...
September 21, 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28932114/spermidine-mediated-poly-lactic-co-glycolic-acid-nanoparticles-containing-fluorofenidone-for-the-treatment-of-idiopathic-pulmonary-fibrosis
#3
Jing Tang, Jianming Li, Guo Li, Haitao Zhang, Ling Wang, Dai Li, Jinsong Ding
Idiopathic pulmonary fibrosis is a progressive, fatal lung disease with poor survival. The advances made in deciphering this disease have led to the approval of different antifibrotic molecules, such as pirfenidone and nintedanib. An increasing number of studies with particles (liposomes, nanoparticles [NPs], microspheres, nanopolymersomes, and nanoliposomes) modified with different functional groups have demonstrated improvement in lung-targeted drug delivery. In the present study, we prepared, characterized, and evaluated spermidine (Spd)-modified poly(lactic-co-glycolic acid) (PLGA) NPs as carriers for fluorofenidone (AKF) to improve the antifibrotic efficacy of this drug in the lung...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28915889/anti-fibrotic-efficacy-of-nintedanib-in-pulmonary-fibrosis-via-the-inhibition-of-fibrocyte-activity
#4
Seidai Sato, Shintaro Shinohara, Shinya Hayashi, Shun Morizumi, Shuichi Abe, Hiroyasu Okazaki, Yanjuan Chen, Hisatsugu Goto, Yoshinori Aono, Hirohisa Ogawa, Kazuya Koyama, Haruka Nishimura, Hiroshi Kawano, Yuko Toyoda, Hisanori Uehara, Yasuhiko Nishioka
BACKGROUND: Nintedanib, a tyrosine kinase inhibitor that is specific for platelet-derived growth factor receptors (PDGFR), fibroblast growth factor receptors (FGFR), and vascular endothelial growth factor receptors (VEGFR), has recently been approved for idiopathic pulmonary fibrosis. Fibrocytes are bone marrow-derived progenitor cells that produce growth factors and contribute to fibrogenesis in the lungs. However, the effects of nintedanib on the functions of fibrocytes remain unclear...
September 15, 2017: Respiratory Research
https://www.readbyqxmd.com/read/28915874/unmet-needs-in-the-treatment-of-idiopathic-pulmonary-fibrosis-insights-from-patient-chart-review-in-five-european-countries
#5
Toby M Maher, Maria Molina-Molina, Anne-Marie Russell, Francesco Bonella, Stéphane Jouneau, Elena Ripamonti, Judit Axmann, Carlo Vancheri
BACKGROUND: Two antifibrotic drugs, pirfenidone and nintedanib, are approved by the European Medicines Agency and the US Food and Drug Administration for the treatment of idiopathic pulmonary fibrosis (IPF). In this analysis, treatment patterns of European patients with IPF were investigated to understand antifibrotic prescribing and identify unmet needs in IPF treatment practice. METHODS: Between February and March 2016, respiratory physicians from France, Germany, Italy, Spain, and the UK participated in an online questionnaire designed to collect information on IPF treatment patterns in patients under their care...
September 15, 2017: BMC Pulmonary Medicine
https://www.readbyqxmd.com/read/28898237/nintedanib-selectively-inhibits-the-activation-and-tumour-promoting-effects-of-fibroblasts-from-lung-adenocarcinoma-patients
#6
M Gabasa, R Ikemori, F Hilberg, N Reguart, J Alcaraz
BACKGROUND: Nintedanib is a clinically approved multikinase receptor inhibitor to treat non-small cell lung cancer with adenocarcinoma (ADC) histology in combination with docetaxel, based on the clinical benefits reported on ADC but not on squamous cell carcinoma (SCC), which are the two most common histologic lung cancer subtypes. METHODS: We examined the potential role of tumour-associated fibroblasts (TAFs) in the differential effects of nintedanib in ADC and SCC...
September 12, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28892431/nintedanib-plus-pemetrexed-cisplatin-in-patients-with-malignant-pleural-mesothelioma-phase-ii-results-from-the-randomized-placebo-controlled-lume-meso-trial
#7
Federica Grosso, Nicola Steele, Silvia Novello, Anna K Nowak, Sanjay Popat, Laurent Greillier, Thomas John, Natasha B Leighl, Martin Reck, Paul Taylor, David Planchard, Jens Benn Sørensen, Mark A Socinski, Ute von Wangenheim, Arsène Bienvenu Loembé, José Barrueco, Nassim Morsli, Giorgio Scagliotti
Purpose LUME-Meso is a phase II/III randomized, double-blind trial designed to assess efficacy and safety of nintedanib plus chemotherapy as first-line treatment of malignant pleural mesothelioma (MPM). Phase II results are reported here. Patients and Methods Chemotherapy-naïve patients with unresectable, nonsarcomatoid MPM (Eastern Cooperative Oncology Group performance status 0 to 1), stratified by histology (epithelioid or biphasic), were randomly assigned in a 1:1 ratio to up to six cycles of pemetrexed and cisplatin plus nintedanib (200 mg twice daily) or placebo followed by nintedanib plus placebo monotherapy until progression...
September 11, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28892311/-how-i-treat-a-patient-with-idiopathic-pulmonary-fibrosis
#8
J Guiot, B Duysinx, O Bonhomme, R Louis, J-L Corhay
Idiopathic pulmonary fibrosis (IPF) is a rare disorder of unknown origin, which is associated with a high mortality and whose incidence has been increasing for several years. Nowadays there are two anti-fibrotic therapies (pirfenidone - nintedanib) known to reduce significantly the decline in respiratory function tests of patients suffering from this condition. The only curative therapeutic option remains the pulmonary transplantation whose accessibility remains limited. Pulmonary rehabilitation is also central in the treatment of patients...
September 2017: Revue Médicale de Liège
https://www.readbyqxmd.com/read/28889759/nintedanib-with-add-on-pirfenidone-in-idiopathic-pulmonary-fibrosis-results-of-the-injourney-trial
#9
Carlo Vancheri, Michael Kreuter, Luca Richeldi, Christopher J Ryerson, Dominique Valeyre, Jan C Grutters, Sabrina Wiebe, Wibke Stansen, Manuel Quaresma, Susanne Stowasser, Wim A Wuyts
RATIONALE: Nintedanib and pirfenidone slow the progression of IPF, but the disease continues to progress. More data are needed on the safety and efficacy of combination therapy with nintedanib and add-on pirfenidone. OBJECTIVES: To investigate safety, tolerability, pharmacokinetic and exploratory efficacy endpoints in patients treated with nintedanib and add-on pirfenidone versus nintedanib alone. METHODS: Patients with IPF and FVC ≥50% predicted at screening who completed a 4-5 week run-in with nintedanib 150 mg bid without dose reduction or treatment interruption were randomized to nintedanib 150 mg bid with add-on pirfenidone (titrated to 801 mg tid), or nintedanib 150 mg bid alone, open-label for 12 weeks...
September 10, 2017: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/28883926/clinical-use-of-nintedanib-in-patients-with-idiopathic-pulmonary-fibrosis
#10
REVIEW
Amy Hajari Case, Peace Johnson
Idiopathic pulmonary fibrosis (IPF) is a rare lung disease characterised by progressive loss of lung function, dyspnoea and cough. IPF has a variable clinical course but a poor prognosis. Nintedanib, a tyrosine kinase inhibitor, is one of two drugs approved for the treatment of IPF. In clinical trials, nintedanib slowed disease progression by reducing the rate of decline in forced vital capacity (FVC) in patients with IPF and mild or moderate lung function impairment. The effect of nintedanib was consistent across patient subgroups defined by baseline characteristics including FVC % predicted, diffusion capacity of the lung for carbon monoxide % predicted and the presence of emphysema...
2017: BMJ Open Respiratory Research
https://www.readbyqxmd.com/read/28883482/low-body-surface-area-predicts-hepatotoxicity-of-nintedanib-in-patients-with-idiopathic-pulmonary-fibrosis
#11
Satoshi Ikeda, Akimasa Sekine, Tomohisa Baba, Yumie Yamanaka, Shinko Sadoyama, Hideaki Yamakawa, Tsuneyuki Oda, Ryo Okuda, Hideya Kitamura, Koji Okudela, Tae Iwasawa, Kenichi Ohashi, Tamiko Takemura, Takashi Ogura
After the commercialization of nintedanib in Japan, a high incidence of hepatotoxicity resulting in treatment interruption was noted in idiopathic pulmonary fibrosis (IPF) patients treated with nintedanib in our hospital. This study aimed to clarify the risk factors for hepatotoxicity of nintedanib. Sixty-eight consecutive cases of IPF newly treated with nintedanib at a dose of 150 mg twice daily from September 2015 to September 2016 were enrolled: 46 patients (67.6%) exhibited aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) elevation and 16 patients (23...
September 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28882160/intrinsic-fluorescence-of-the-clinically-approved-multikinase-inhibitor-nintedanib-reveals-lysosomal-sequestration-as-resistance-mechanism-in-fgfr-driven-lung-cancer
#12
Bernhard Englinger, Sebastian Kallus, Julia Senkiv, Daniela Heilos, Lisa Gabler, Sushilla van Schoonhoven, Alessio Terenzi, Patrick Moser, Christine Pirker, Gerald Timelthaler, Walter Jäger, Christian R Kowol, Petra Heffeter, Michael Grusch, Walter Berger
BACKGROUND: Studying the intracellular distribution of pharmacological agents, including anticancer compounds, is of central importance in biomedical research. It constitutes a prerequisite for a better understanding of the molecular mechanisms underlying drug action and resistance development. Hyperactivated fibroblast growth factor receptors (FGFRs) constitute a promising therapy target in several types of malignancies including lung cancer. The clinically approved small-molecule FGFR inhibitor nintedanib exerts strong cytotoxicity in FGFR-driven lung cancer cells...
September 7, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28881856/strategies-targeting-angiogenesis-in-advanced-non-small-cell-lung-cancer
#13
REVIEW
Jun Wang, Jianpeng Chen, Yan Guo, Baocheng Wang, Huili Chu
Tumor angiogenesis is a frequent event in the development and progression of non-small cell lung cancer (NSCLC) and has been identified as a promising therapeutic target. The vascular endothelial growth factor (VEGF) family and other angiogenic factors, including fibroblast growth factor and platelet-derived growth factor, promote the growth of newly formed vessels from preexisting vessels and change the tumor microenvironment. To date, two antiangiogenic monoclonal antibodies, bevacizumab and ramucirumab, which target VEGF-A and its receptor VEGF receptor-2, respectively, have been approved for the treatment of locally advanced or metastatic NSCLC when added to first-line standard chemotherapy...
August 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28861727/managing-idiopathic-pulmonary-fibrosis-which-drug-for-which-patient
#14
Conal Hayton, Nazia Chaudhuri
Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic lung disease with high mortality. Two novel antifibrotic agents, pirfenidone and nintedanib, have received licences for use in IPF in recent years. Phase III, multinational, randomised control trials have provided evidence that both drugs reduce decline in forced vital capacity (FVC) over time, while further post hoc studies have suggested that both pirfenidone and nintedanib can be efficacious, regardless of age and severity of baseline lung function...
August 31, 2017: Drugs & Aging
https://www.readbyqxmd.com/read/28855577/quantitative-and-organisational-changes-in-mature-extracellular-matrix-revealed-through-high-content-imaging-of-total-protein-fluorescently-stained-in-situ
#15
Gill Holdsworth, Hélène Bon, Marianne Bergin, Omar Qureshi, Ross Paveley, John Atkinson, Linghong Huang, Roohi Tewari, Breda Twomey, Timothy Johnson
Fibrosis is a common driver of end-stage organ failure in most organs. It is characterised by excessive accumulation of extracellular matrix (ECM) proteins. Therapeutic options are limited and novel treatments are urgently required, however current cell-based high-throughput screening (HTS) models to identify molecules affecting ECM accumulation are limited in their relevance or throughput. We report a novel sensitive approach which combines in situ fluorescent staining of accumulated decellularised ECM proteins with automated high-content microscopy...
August 30, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28852519/fatal-diffuse-alveolar-haemorrhage-mimicking-acute-exacerbation-in-idiopathic-pulmonary-fibrosis-treated-with-nintedanib
#16
Keishi Sugino, Yasuhiko Nakamura, Muneyuki Sekiya, Hiroshi Kobayashi, Kazutoshi Shibuya, Sakae Homma
A 75-year-old man was referred to our hospital with a 1-year history of persistent dry cough and progressive dyspnoea on exertion. He was treated with aspirin due to thrombosis of internal carotid artery. He was diagnosed with idiopathic pulmonary fibrosis (IPF)/usual interstitial pneumonia (UIP), and started on inhaled N-acetylcysteine therapy and pirfenidone. Since his clinical condition progressively deteriorated after 6 months, he was switched from pirfenidone to nintedanib. As a result, his general condition worsened rapidly...
November 2017: Respirology Case Reports
https://www.readbyqxmd.com/read/28845557/treatment-of-idiopathic-pulmonary-fibrosis-in-australia-and-new-zealand-a-position-statement-from-the-thoracic-society-of-australia-and-new-zealand-and-the-lung-foundation-australia
#17
Helen E Jo, Lauren K Troy, Gregory Keir, Daniel C Chambers, Anne Holland, Nicole Goh, Margaret Wilsher, Sally de Boer, Yuben Moodley, Christopher Grainge, Helen Whitford, Sally Chapman, Paul N Reynolds, Ian Glaspole, David Beatson, Leonie Jones, Peter Hopkins, Tamera J Corte
Idiopathic pulmonary fibrosis (IPF) is a fibrosing interstitial lung disease (ILD) of unknown aetiology with a median survival of only 2-5 years. It is characterized by progressive dyspnoea and worsening lung function, ultimately resulting in death. Until recently, there were no effective therapies for IPF; however, with the publication of two landmark clinical trials in 2014, the anti-fibrotic therapies, nintedanib and pirfenidone, have gained widespread approval. This position paper aims to highlight the current evidence for the treatment of IPF, with particular application to the Australian and New Zealand population...
August 27, 2017: Respirology: Official Journal of the Asian Pacific Society of Respirology
https://www.readbyqxmd.com/read/28818987/response-assessment-of-68-ga-dota-e-c-rgdfk-2-pet-ct-for-lung-adenocarcinoma-patients-treated-with-nintedanib-plus-docetaxel
#18
Oscar Arrieta, Francisco O Garcia-Perez, David Michel-Tello, Laura-Alejandra Ramirez-Tirado, Quetzali Pitalua-Cortes, Graciela Cruz-Rico, Eleazar-Omar Macedo-Perez, Andres F Cardona, Jaime de la Garza-Salazar
Nintedanib is an oral angiokinase inhibitor used as a second-line treatment for non-small-cell lung cancer (NSCLC). New radiotracers, such as (68)Ga-DOTA-E-[c(RGDfK)]2, that target αvβ3 integrin might impact the clinical practice as a non-invasive method for assessing angiogenesis inhibitors. Methods: From July 2014 through October 2015, 38 patients received second-line nintedanib plus docetaxel. All the patients underwent PET/CT with (68)Ga-DOTA-E-[c(RGDfK)]2 radiotracer and blood-sample tests to quantify angiogenesis factors (FGF, VEGF and PDGF-AB) prior to and after completing 2 therapy cycles...
August 17, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/28814429/nintedanib-inhibits-macrophage-activation-and-ameliorates-vascular-and-fibrotic-manifestations-in-the-fra2-mouse-model-of-systemic-sclerosis
#19
Jingang Huang, Christiane Maier, Yun Zhang, Alina Soare, Clara Dees, Christian Beyer, Ulrike Harre, Chih-Wei Chen, Oliver Distler, Georg Schett, Lutz Wollin, Jörg H W Distler
BACKGROUND: Nintedanib is an inhibitor targeting platelet-derived growth factor receptor, fibroblast growth factor receptor and vascular endothelial growth factor receptor tyrosine kinases that has recently been approved for the treatment of idiopathic pulmonary fibrosis. The aim of this study was to analyse the effects of nintedanib in the fos-related antigen-2 (Fra2) mouse model of systemic sclerosis (SSc). METHODS: The effects of nintedanib on pulmonary arterial hypertension with proliferation of pulmonary vascular smooth muscle cells (PVSMCs) and luminal occlusion, on microvascular disease with apoptosis of microvascular endothelial cells (MVECs) and on fibroblast activation with myofibroblast differentiation and accumulation of extracellular matrix were analysed...
August 16, 2017: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/28798401/the-tyrosine-kinase-inhibitor-nintedanib-activates-shp-1-and-induces-apoptosis-in-triple-negative-breast-cancer-cells
#20
Chun-Yu Liu, Tzu-Ting Huang, Pei-Yi Chu, Chun-Teng Huang, Chia-Han Lee, Wan-Lun Wang, Ka-Yi Lau, Wen-Chun Tsai, Tzu-I Chao, Jung-Chen Su, Ming-Huang Chen, Chung-Wai Shiau, Ling-Ming Tseng, Kuen-Feng Chen
Triple-negative breast cancer (TNBC) remains difficult to treat and urgently needs new therapeutic options. Nintedanib, a multikinase inhibitor, has exhibited efficacy in early clinical trials for HER2-negative breast cancer. In this study, we examined a new molecular mechanism of nintedanib in TNBC. The results demonstrated that nintedanib enhanced TNBC cell apoptosis, which was accompanied by a reduction of p-STAT3 and its downstream proteins. STAT3 overexpression suppressed nintedanib-mediated apoptosis and further increased the activity of purified SHP-1 protein...
August 11, 2017: Experimental & Molecular Medicine
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