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https://www.readbyqxmd.com/read/29769293/emerging-multitarget-tyrosine-kinase-inhibitors-in-the-treatment-of-neuroendocrine-neoplasms
#1
Federica Grillo, Tullio Florio, Francesco Ferraù, Elda Kara, Giuseppe Fanciulli, Antongiulio Faggiano, Annamaria A L Colao
In the last few years, the therapeutic approach for neuroendocrine neoplasms (NENs) has changed dramatically following the approval of several novel targeted treatments. The multi-target tyrosine kinase inhibitor (MTKI), sunitinib malate, has been approved by regulatory agencies in pancreatic NENs. The MTKI class, however, includes several other molecules (approved for other conditions), which are currently being studied in NENs. An in depth review on the studies published on the following MTKIs in neuroendocrine tumours: axitinib, cabozantinib, famitinib, lenvatinib, nintedanib, pazopanib, sorafenib and sulfatinib was performed...
May 16, 2018: Endocrine-related Cancer
https://www.readbyqxmd.com/read/29763335/nintedanib-in-severe-pulmonary-arterial-hypertension
#2
Manuel J Richter, Jan Ewert, Friedrich Grimminger, Hossein Ardeschir Ghofrani, Baktybek Kojonazarov, Aleksandar Petrovic, Werner Seeger, Ralph T Schermuly, Khodr Tello, Henning Gall
No abstract text is available yet for this article.
May 15, 2018: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/29748017/antiangiogenic-therapy-for-patients-with-aggressive-or-refractory-advanced-non-small-cell-lung-cancer-in-the-second-line-setting
#3
REVIEW
Martin Reck, Marina Chiara Garassino, Martina Imbimbo, Frances A Shepherd, Mark A Socinski, Jin-Yuan Shih, Anne Tsao, Pablo Lee, Katherine B Winfree, Andreas Sashegyi, Rebecca Cheng, Rocio Varea, Benjamin Levy, Edward Garon
A majority of patients with advanced or metastatic non-small cell lung cancer (NSCLC) will experience disease progression after first-line therapy. Patients who have advanced NSCLC that is especially aggressive, which is defined as disease that rapidly progresses on first-line treatment or disease that is refractory to first-line treatment, have a critical unmet medical need. These patients have a poor prognosis in the second-line setting. Several studies have recently shown that treatment with an antiangiogenic therapy may benefit these patients...
June 2018: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/29748012/a-phase-i-study-of-nintedanib-combined-with-cisplatin-gemcitabine-as-first-line-therapy-for-advanced-squamous-non-small-cell-lung-cancer-lume-lung-3
#4
Martin Forster, Allan Hackshaw, Tommaso De Pas, Manuel Cobo, Pilar Garrido, Yvonne Summers, Anne-Marie C Dingemans, Michael Flynn, David Schnell, Ute von Wangenheim, Arsene-Bienvenu Loembé, Rolf Kaiser, Siow Ming Lee
BACKGROUND: There are limited treatment options for squamous non-small cell lung cancer (sqNSCLC) and prognosis remains poor. The safety and pharmacokinetics (PK) of nintedanib, a triple angiokinase inhibitor, plus cisplatin/gemcitabine as first-line treatment for advanced sqNSCLC patients, were evaluated. MATERIALS AND METHODS: A phase I, dose-escalation study administering drugs in a 21-day cycle: cisplatin (75 mg/m2 , Day 1), gemcitabine (1250 mg/m2 , Days 1 and 8) and nintedanib (Days 2-7, 9-21) were given for 4-6 cycles, followed by monotherapy until disease progression or adverse events (AEs)...
June 2018: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/29724868/nintedanib-is-active-in-malignant-pleural-mesothelioma-cell-models-and-inhibits-angiogenesis-and-tumor-growth-in-vivo
#5
Viktoria Laszlo, Zsuzsanna Valko, Ildiko Kovacs, Judit Ozsvar, Mir Alireza Hoda, Thomas Klikovits, Dora Lakatos, András Czirók, Tamas Garay, Alexander Stiglbauer, Thomas Hans Helbich, Marion Groger, Jozsef Tovari, Walter Klepetko, Christine Pirker, Michael Grusch, Walter Berger, Frank Hilberg, Balazs Hegedus, Balazs Dome
PURPOSE: Malignant pleural mesothelioma (MPM) is an aggressive thoracic tumor type with limited treatment options and poor prognosis. The angiokinase inhibitor nintedanib has shown promising activity in the LUME-Meso phase 2 MPM trial and thus is currently being evaluated in the confirmatory LUME-Meso phase 3 trial. However, the anti-MPM potential of nintedanib has not been studied in the preclinical setting. EXPERIMENTAL DESIGN: We have examined the antineoplastic activity of nintedanib in various in vitro and in vivo models of human MPM...
May 3, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29721603/pneumatosis-intestinalis-associated-with-the-tyrosine-kinase-inhibitor-nintedanib
#6
Armeen Poor, Sidney S Braman
No abstract text is available yet for this article.
May 2, 2018: Lung
https://www.readbyqxmd.com/read/29718783/an-update-on-emerging-drugs-for-the-treatment-of-idiopathic-pulmonary-fibrosis
#7
Shambhu Aryal, Steven D Nathan
Idiopathic pulmonary fibrosis is a chronic, progressive fibrotic lung disease of unknown etiology associated with a high morbidity and mortality. The hallmark of the disease is impaired healing after alveolar epithelial injury in the setting of a genetic predisposition. Development of two new drugs has changed the landscape of the treatment of IPF but more work is needed to improve outcomes and improve survival. Areas covered: The development of two antifibrotic agents, nintedanib and pirfenidone has been an exciting landmark in the treatment of IPF...
May 8, 2018: Expert Opinion on Emerging Drugs
https://www.readbyqxmd.com/read/29695053/vegf-vascular-endothelial-growth-factor-and-fibrotic-lung-disease
#8
REVIEW
Shaney L Barratt, Victoria A Flower, John D Pauling, Ann B Millar
Interstitial lung disease (ILD) encompasses a group of heterogeneous diseases characterised by varying degrees of aberrant inflammation and fibrosis of the lung parenchyma. This may occur in isolation, such as in idiopathic pulmonary fibrosis (IPF) or as part of a wider disease process affecting multiple organs, such as in systemic sclerosis. Anti-Vascular Endothelial Growth Factor (anti-VEGF) therapy is one component of an existing broad-spectrum therapeutic option in IPF (nintedanib) and may become part of the emerging therapeutic strategy for other ILDs in the future...
April 24, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29694983/nintedanib-in-severe-idiopathic-pulmonary-fibrosis-effectiveness-through-compassion
#9
Argyrios Tzouvelekis, Demosthenes Bouros
No abstract text is available yet for this article.
April 25, 2018: Respiration; International Review of Thoracic Diseases
https://www.readbyqxmd.com/read/29663427/surfactant-protein-d-alleviates-eosinophil-mediated-airway-inflammation-and-remodeling-in-patients-with-aspirin-exacerbated-respiratory-disease
#10
Youngwoo Choi, Dong-Hyun Lee, Trinh Hoang Kim Tu, Ga-Young Ban, Hanki Park, Yoo Seob Shin, Seung-Hyun Kim, Hae-Sim Park
BACKGROUND: Surfactant protein D (SPD) is a member of the collectin family that lines the airway epithelial cells with host defense. However, the role of SPD in the pathogenesis of aspirin-exacerbated respiratory disease (AERD) is still unclear. METHODS: The serum SPD level was measured in patients with AERD (n=336), those with aspirin-tolerant asthma (ATA, n=442), and healthy controls (HC, n=104). Polymorphisms of SFTPD in the study subjects were analyzed. The effect of LTE4 on SPD production through eosinophil infiltration was investigated in BALB/c mice...
April 16, 2018: Allergy
https://www.readbyqxmd.com/read/29601564/-nintedanib-in-the-treatment-of-fibrosing-interstital-lung-diseases
#11
REVIEW
Katarzyna Lewandowska
Nintedanib is an intracellular tyrosine kinase inhibitor approved in a treatment of idiopathic pulmonary fibrosis. It reduces the annual rate of forced vital capacity decline by approximately 50%, that results in slowing of disease progression. The drug also reduces the incidence of acute exacerbations of idiopathic pulmonary fibrosis. The efficacy of nintedanib was the same in different groups of patients, irrespectively to disease status, age, gender and race. The most frequent side effects were gastrointestinal, i...
March 27, 2018: Polski Merkuriusz Lekarski: Organ Polskiego Towarzystwa Lekarskiego
https://www.readbyqxmd.com/read/29601563/-advances-in-differential-diagnosis-and-treatment-of-patients-with-sarcoidosis
#12
REVIEW
Tadeusz Płusa
The implementation of treatment in patients with sarcoidosis (SA) must be associated with the certainty of diagnosis, which is difficult due to the lack of unambiguous criteria. Finding the presence of noncaseating granulomas in bioptic material is not always indicative of SA. The main point of SA's diagnosis is the level of its activity, because only patients in the active stage should be qualified for treatment. In therapy, glucocorticosteroids or second-line drugs - methotrexate or azathioprine are still recommended...
March 27, 2018: Polski Merkuriusz Lekarski: Organ Polskiego Towarzystwa Lekarskiego
https://www.readbyqxmd.com/read/29587263/a-real-life-multicenter-national-study-on-nintedanib-in-severe-idiopathic-pulmonary-fibrosis
#13
Sergio Harari, Antonella Caminati, Venerino Poletti, Marco Confalonieri, Stefano Gasparini, Donato Lacedonia, Fabrizio Luppi, Alberto Pesci, Alfredo Sebastiani, Paolo Spagnolo, Carlo Vancheri, Elisabetta Balestro, Martina Bonifazi, Stefania Cerri, Federica De Giacomi, Rossana Della Porta, Maria Pia Foschino Barbaro, Annalisa Fui, Patrizio Pasquinelli, Roberta Rosso, Sara Tomassetti, Claudia Specchia, Paola Rottoli
BACKGROUND: Two therapeutic options are currently available for patients with mild-to-moderate idiopathic pulmonary fibrosis (IPF): pirfenidone and nintedanib. To date, there is still insufficient data on the efficacy of these 2 agents in patients with more severe disease. OBJECTIVES: This national, multicenter, retrospective real-life study was intended to determine the impact of nintedanib on the treatment of patients with severe IPF. METHODS: All patients included had severe IPF and had to have at least 6 months of follow-up before and at least 6 months of follow-up after starting nintedanib...
March 27, 2018: Respiration; International Review of Thoracic Diseases
https://www.readbyqxmd.com/read/29565707/ev-vivo-organ-culture-as-potential-prioritization-tool-for-breast-cancer-targeted-therapy
#14
Albert Grinshpun, Nancy Gavert, Roy Zvi Granit, Hadas Masuri, Ittai Ben-Porath, Shani Breuer, Aviad Zick, Shai Rosenberg, Myriam Maoz, Avital Granit, Eli Pikarsky, Ravid Strausmman, Tamar Peretz, Amir Sonnenblick
The growing use of genomic testing presents new treatment options but also new dilemmas. We describe here a heavily-pretreated metastatic triple negative breast cancer patient who failed to respond to conventional treatment. Genomic analyses were performed that discovered several targetable alterations (e.g. FGFR1, CDK6, INSR) and created a clinical challenge - which target to target first? Our solution to this relatively common scenario was using ex-vivo organ culture (EVOC) system to prioritize treatment directed toward the best molecular target...
March 22, 2018: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/29564136/safety-of-nintedanib-before-lung-transplant-an-italian-case-series
#15
Elisabetta Balestro, Paolo Solidoro, Piercarlo Parigi, Massimo Boffini, Alessandro Lucianetti, Federico Rea
Idiopathic pulmonary fibrosis (IPF) is a progressive, fatal disease that can only be cured by lung transplantation. Pharmacological agents play a role in preserving lung function and prolonging survival until a suitable donor organ becomes available. However, data on the effects of newer antifibrotic therapies on lung transplantation outcomes in IPF patients are lacking. The nine patients included in this case series were treated with nintedanib 150 mg twice daily for 3-30 (mean 13 ± 9) months before lung transplant surgery...
May 2018: Respirology Case Reports
https://www.readbyqxmd.com/read/29563636/a-multicentre-open-label-phase-i-randomised-phase-ii-study-to-evaluate-safety-pharmacokinetics-and-efficacy-of-nintedanib-vs-sorafenib-in-european-patients-with-advanced-hepatocellular-carcinoma
#16
D H Palmer, Y T Ma, M Peck-Radosavljevic, P Ross, J Graham, L Fartoux, A Deptala, M Studeny, D Schnell, J Hocke, A-B Loembé, T Meyer
BACKGROUND: This multicentre, open-label, phase-I/randomised phase-II trial evaluated safety, pharmacokinetics, maximum-tolerated-dose (MTD) per dose-limiting toxicities (DLTs), and efficacy of nintedanib vs. sorafenib in European patients with unresectable advanced hepatocellular carcinoma (aHCC). METHODS: Phase I: Patients were stratified into two groups per baseline aminotransferase/alanine aminotransferase and Child-Pugh score; MTD was determined. Phase II: Patients were randomised 2:1 to nintedanib (MTD) or sorafenib (400-mg bid) in 28-day cycles until intolerance or disease progression...
March 22, 2018: British Journal of Cancer
https://www.readbyqxmd.com/read/29543042/nintedanib-reduces-pulmonary-fibrosis-in-a-model-of-rheumatoid-arthritis-associated-interstitial-lung-disease
#17
Elizabeth F Redente, Martin A Aguilar, Bart P Black, Benjamin Edelman, Ali Bahadur, Stephen M Humphries, David A Lynch, Lutz Wollin, David W H Riches
Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) develops in approximately 20% of patients with RA. SKG mice, which are genetically prone to developing autoimmune arthritis, develop a pulmonary interstitial pneumonia that resembles human cellular and fibrotic non-specific interstitial pneumonia. Nintedanib, a tyrosine kinase inhibitor approved for the treatment of idiopathic pulmonary fibrosis, has been shown to reduce lung function decline. Therefore, we investigated the effect of nintedanib on the development of pulmonary fibrosis and joint disease in female SKG mice with arthritis induced by intraperitoneal injection of zymosan (5 mg)...
March 15, 2018: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/29532550/fibroblast-matrix-interplay-nintedanib-and-pirfenidone-modulate-the-effect-of-ipf-fibroblast-conditioned-matrix-on-normal-fibroblast-phenotype
#18
Gali Epstein Shochet, Lutz Wollin, David Shitrit
BACKGROUND AND OBJECTIVE: Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease with poor prognosis. Activated fibroblasts are the key effector cells in fibrosis, producing excessive amounts of collagen and extracellular matrix (ECM) proteins. Whether the ECM conditioned by IPF fibroblasts determines the phenotype of naïve fibroblasts is difficult to explore. METHODS: IPF-derived primary fibroblasts were cultured on Matrigel and then cleared using ammonium hydroxide, creating an IPF-conditioned matrix (CM)...
March 12, 2018: Respirology: Official Journal of the Asian Pacific Society of Respirology
https://www.readbyqxmd.com/read/29500603/effects-of-ketoconazole-and-rifampicin-on-the-pharmacokinetics-of-nintedanib-in-healthy-subjects
#19
Doreen Luedtke, Kristell Marzin, Arvid Jungnik, Ute von Wangenheim, Claudia Dallinger
BACKGROUND: Nintedanib is a substrate for p-glycoprotein which can impact bioavailability. We investigated the effects of ketoconazole, a p-glycoprotein inhibitor, and rifampicin, a p-glycoprotein inducer, on the pharmacokinetics of nintedanib. METHODS: In the ketoconazole study, 34 healthy subjects received nintedanib 50 mg orally alone and 1 h after the last dose of ketoconazole given orally at a dose of 400 mg once daily for 3 days in 1 of 2 randomized sequences...
March 2, 2018: European Journal of Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/29490307/real-world-experience-with-nintedanib-in-patients-with-idiopathic-pulmonary-fibrosis
#20
Eva Brunnemer, Julia Wälscher, Svenja Tenenbaum, Julia Hausmanns, Karen Schulze, Marianne Seiter, Claus Peter Heussel, Arne Warth, Felix J F Herth, Michael Kreuter
BACKGROUND: Nintedanib, an oral tyrosine kinase inhibitor, has been shown to slow down the progression of idiopathic pulmonary fibrosis (IPF) in two randomised placebo-controlled trials by reducing the annual decline in forced vital capacity (FVC). However, real-world experience is limited. OBJECTIVE: To assess the efficacy and safety of nintedanib in a large cohort of patients treated at a tertiary referral site for interstitial lung diseases. METHODS: The records of patients with a confirmed diagnosis of IPF were reviewed...
2018: Respiration; International Review of Thoracic Diseases
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