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Burçin Çelik, Zeynep Pelin Sürücü, Volkan Yılmaz, Hale Kefeli Çelik
Secondary spontaneous pneumothorax almost always develops secondary to an underlying lung disease. A pneumothorax secondary to a malignancy is very rare, and is observed most frequently in soft tissue sarcomas. Pazopanib, a tyrosine kinase inhibitor, is used in metastatic soft tissue sarcomas treatment. The rate of pneumothorax that is caused by pazopanib is about 14% in the literature. The patient being presented in this article underwent surgery for soft tissue sarcoma, postoperatively received pazopanib (Votrient® 400 mg, oral, Glaxo Group Ltd, Brentford, UK) treatment due to widespread bilateral lung metastases, and developed synchronous spontaneous pneumothorax...
January 2018: Turkish Thoracic Journal
James E Frampton
Pazopanib (Votrient®), an orally administered multi-targeted tyrosine kinase inhibitor that predominantly inhibits vascular endothelial growth factor receptor-1, -2 and -3, platelet-derived growth factor receptor-α and -β, and the stem cell factor receptor c-Kit, is approved in the EU, the USA and other countries for the treatment of advanced renal cell carcinoma (RCC). In randomized controlled trials in patients with advanced, predominantly clear-cell RCC, pazopanib significantly improved progression-free survival (PFS) compared with placebo in both treatment-naïve and cytokine-pretreated patients and, as a first-line therapy, was noninferior to intermittent sunitinib with respect to PFS...
August 2017: Targeted Oncology
L V Spirina, E A Usynin, I V Kondakova, Z A Yurmazov, E M Slonimskaya
We analyzed the dynamics of the expression of transcription factors, VEGF and its receptor VEGFR2, serine-threonine protein kinase mTOR and activity of proteasome and calpain in patients with metastatic renal cancer during therapy with tyrosine kinase inhibitor Votrient and mTOR blocker Afinitor. The expression of hypoxic nuclear factor HIF-1α in the tumor tissue decreased during therapy with the target preparations. The decrease of VEGF and its receptor VEGFR2 was observed only in patients treated with mTOR inhibitor...
April 2016: Bulletin of Experimental Biology and Medicine
Vivek Subbiah, Caitlin McMahon, Shreyaskumar Patel, Ralph Zinner, Elvio G Silva, Julia A Elvin, Ishwaria M Subbiah, Chimela Ohaji, Dhakshina Moorthy Ganeshan, Deepa Anand, Charles F Levenback, Jenny Berry, Tim Brennan, Juliann Chmielecki, Zachary R Chalmers, John Mayfield, Vincent A Miller, Philip J Stephens, Jeffrey S Ross, Siraj M Ali
BACKGROUND: Recurrent, metastatic mesenchymal myxoid tumors of the gynecologic tract present a management challenge as there is minimal evidence to guide systemic therapy. Such tumors also present a diagnostic dilemma, as myxoid features are observed in leiomyosarcomas, inflammatory myofibroblastic tumors (IMT), and mesenchymal myxoid tumors. Comprehensive genomic profiling was performed in the course of clinical care on a case of a recurrent, metastatic myxoid uterine malignancy (initially diagnosed as smooth muscle tumor of uncertain malignant potential (STUMP)), to guide identify targeted therapeutic options...
June 11, 2015: Journal of Hematology & Oncology
Jane L Roberts, Mehrad Tavallai, Aida Nourbakhsh, Abigail Fidanza, Tanya Cruz-Luna, Elizabeth Smith, Paul Siembida, Pascale Plamondon, Kelly A Cycon, Christopher D Doern, Laurence Booth, Paul Dent
Prior tumor cell studies have shown that the drugs sorafenib (Nexavar) and regorafenib (Stivarga) reduce expression of the chaperone GRP78. Sorafenib/regorafenib and the multi-kinase inhibitor pazopanib (Votrient) interacted with sildenafil (Viagra) to further rapidly reduce GRP78 levels in eukaryotes and as single agents to reduce Dna K levels in prokaryotes. Similar data were obtained in tumor cells in vitro and in drug-treated mice for: HSP70, mitochondrial HSP70, HSP60, HSP56, HSP40, HSP10, and cyclophilin A...
October 2015: Journal of Cellular Physiology
Arie J Verschoor, Hans Gelderblom
BACKGROUND: Recently, the phase III PALETTE study introduced pazopanib (Votrient®) as treatment for adult patients with locally advanced or metastatic non-liposarcoma soft tissue sarcoma after prior treatment with doxorubicin and/or ifosfamide. Pneumothorax was reported as adverse event in 8 of 246 treated patients (3.3%) in that study. This case series presents the incidence and clinic of this complication in the Leiden University Medical Centre. CASES: Forty-three patients were treated with pazopanib of which six patients (14...
2014: Clinical Sarcoma Research
Tulay Akman, Oytun Erbas, Levent Akman, Ahmet U Yilmaz
Background: Pazopanib (PZP) may induce prolonged cardiac repolarization and proarrhythmic effects, similarly to other tyrosine kinase inhibitors. Objectives: To demonstrate PZP-induced prolonged cardiac repolarization and proarrhythmic electrophysiological effects and to investigate possible preventive effects of metoprolol and diltiazem on ECG changes (prolonged QT) in an experimental rat model. Methods: Twenty-four Sprague-Dawley adult male rats were randomly assigned to 4 groups (n = 6). The first group (normal group) received 4 mL of tap water and the other groups received 100 mg/kg of PZP (Votrient® tablet) perorally, via orogastric tubes...
November 2014: Arquivos Brasileiros de Cardiologia
Zofia F Bielecka, Anna M Czarnecka, Wojciech Solarek, Anna Kornakiewicz, Cezary Szczylik
Clear - cell renal cell carcinoma (ccRCC) is a histological subtype of renal cell carcinoma - the most prevalent adult kidney cancer. Causes of ccRCC are not completely understood and therefore number of available therapies is limited. As a consequence of tumor chemo- and radioresistance as well as restrictions in offered targeted therapies, overall response rate is still unsatisfactory. Moreover, a significant group of patients (circa 1/4) does not respond to the targeted first-line treatment, while in other cases, after an initial period of stable improvement, disease progression occurs...
December 2014: Current Signal Transduction Therapy
Paul L McCormack
Pazopanib (Votrient(®)) is an orally administered multi-tyrosine kinase inhibitor that is approved in the EU, the US and other countries for the treatment of advanced renal cell carcinoma. Pazopanib predominantly inhibits vascular endothelial growth factor receptor-1, -2 and -3, platelet-derived growth factor receptor-α and -β, and the stem cell factor receptor c-Kit, resulting in inhibition of tumour angiogenesis, cell growth and survival. In randomized controlled trials in patients with advanced, predominantly clear-cell, renal cell carcinoma, progression-free survival (PFS) and the objective response rate were significantly greater in pazopanib recipients than in placebo recipients (VEG105192 trial), and pazopanib was noninferior to sunitinib with respect to PFS (COMPARZ study)...
July 2014: Drugs
Raffaele Ratta, Daniele Santini
Renal cell carcinoma is the most common type of kidney cancer in adults. It accounts for approximately 3% of adult malignancies and 90-95% of neoplasms arising from the kidney. At the moment several biological agents are used for the treatment of metastatic renal cell carcinoma. We describe the case of a man who has been treated with pazopanib (Votrient) for metastatic renal cell carcinoma since July 2011. At the time of writing, the patient is still receiving treatment (29 months) and is showing a long-lasting response with a favorable safety profile...
March 2014: Tumori
Lindsey E Dayer, Laura F Hutchins, Jill T Johnson
Metastatic melanoma has a median length of survival after diagnosis of 6-9 months. Unfortunately, the National Comprehensive Cancer Network clinical practice guidelines for treating stage IV, unresectable, metastatic melanoma are limited with regard to treatment options. Pazopanib (Votrient™) is FDA-approved for advanced soft tissue sarcoma and advanced renal cell carcinoma. Limited research exists for using pazopanib in the treatment of metastatic melanoma. We present five cases in which pazopanib was used in combination with paclitaxel ± carboplatin for treatment of unresectable, metastatic melanoma...
June 2015: Journal of Oncology Pharmacy Practice
Harry A Drabkin
Pazopanib (Votrient™, GlaxoSmithKline), a multi-kinase inhibitor with activity against VEGFR and other receptors, was recently approved by the FDA for the treatment of advanced renal cell carcinoma (RCC). Here, we review the history of its development, together with an overview of VEGF and its receptors and co-receptors. Results from selected clinical trial data in RCC and other malignant diseases are presented. Based on available evidence, pazopanib is an effective VEGFR inhibitor with demonstrable clinical activity in metastatic RCC and promising activity in other diseases...
March 12, 2010: Open Access Journal of Urology
Yanli Deng, Caroline Sychterz, A Benjamin Suttle, Mohammed M Dar, David Bershas, Kitaw Negash, Yanwen Qian, Emile P Chen, Peter D Gorycki, May Y K Ho
1. Pazopanib (Votrient) is an oral tyrosine kinase inhibitor that was recently approved for the treatment of renal cell carcinoma and soft tissue sarcoma. 2. In this two-part study, we investigated the metabolism, disposition of [(14)C]pazopanib, and the oral bioavailability of pazopanib tablets in patients with advanced cancer. 3. In part A, three men each received a single oral dose of [(14)C]pazopanib in suspension (400 mg, 70 µCi). Pazopanib was the predominant drug-related component in circulation. Two metabolites derived from hydroxylation and one from N-demethylation were also circulating, but were minor, each accounting for <5% of plasma radioactivity...
May 2013: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
Jaap Verweij, Stefan Sleijfer
INTRODUCTION: Pazopanib (GW786034, Votrient®) is a vascular endothelial growth factor receptor-focused multi-tyrosine kinase inhibitor involved in inhibiting the angiogenesis pathway. The agent was recently registered for use in soft tissue sarcomas, a group of diseases with a major unmet medical need. AREAS COVERED: The relevance of angiogenesis in soft tissue sarcomas is discussed. These data were the basis to decide on the development of pazopanib in these diseases...
May 2013: Expert Opinion on Pharmacotherapy
Miroslav Murár, Gabriela Addová, Andrej Boháč
BACKGROUND: 5-(Ethylsulfonyl)-2-methoxyaniline (5) is part of the structure in 131 compounds possessing different biological activities. In most cases, they have antitumor properties (112 compounds). Other compounds are described as cardiovascular agents, ion-channel blockers, nervous-system blockers, anti-inflammatory agents, or antidiabetic, antiosteoporotic and hypolipemic species. Compound 5 is a precursor of different protein-kinase inhibitors or enzyme modulators (EGFR, PDGFR, ckit, CDK 2 and 4, MMPs 2, 3, 9 and 13, etc...
2013: Beilstein Journal of Organic Chemistry
Hiroyuki Arai, Nobuaki Fukasawa, Fumie Ueta
No abstract text is available yet for this article.
January 2013: Nihon Yakurigaku Zasshi. Folia Pharmacologica Japonica
C Gennigens, G Jerusalem
Renal cell carcinoma accounts for 3% of all malignant tumors. Until a few years ago, immunotherapy (Interferon and/or Interleukin-2) was the only approved systemic treatment in the metastatic setting. Better knowledge of renal cell cancer biology drew attention on the fundamental role of angiogenesis. Several strategies targeting angiogenesis have been developed including VEGF and VEGFR inhibitors. They are now the standard treatment in first and second line. Pazopanib, a VEGFR tyrosine kinase inhibitor, is one of the treatment options recommended for patients with metastatic renal cell carcinoma, in first line and after cytokines failure...
July 2012: Revue Médicale de Liège
Howard A Burris, Afshin Dowlati, Rebecca A Moss, Jeffrey R Infante, Suzanne F Jones, David R Spigel, Kelly T Levinson, Diana Lindquist, Shelby D Gainer, Mohammed M Dar, A Benjamin Suttle, Howard A Ball, Antoinette R Tan
Several phase III trials have shown that the addition of an antiangiogenic agent to conventional chemotherapy can improve clinical benefit in patients with advanced solid tumors. This study examined the feasibility of combining pazopanib (Votrient), an oral antiangiogenic agent, with paclitaxel and carboplatin. This 3 + 3 dose-escalation phase I study evaluated the maximum-tolerated regimen (MTR) of daily pazopanib in combination with paclitaxel 175 mg/m(2) and carboplatin [dosed at area under the curve (AUC) 5 or 6] given every 21 days in patients with advanced solid tumors...
August 2012: Molecular Cancer Therapeutics
Amy M Pick, Kelly K Nystrom
BACKGROUND: Renal cell carcinoma (RCC) is the most common cancer in the kidneys. Until 2005, treatment options were limited to immunotherapy. Since that time, there have been numerous targeted therapy agents approved with improved efficacy toward RCC. Pazopanib is a multi-tyrosine kinase inhibitor that was approved by the US Food and Drug Administration in October 2009 and by the European Medicines Agency in June 2010 for the treatment of metastatic RCC. OBJECTIVE: The objective of this report was to review pazopanib's mechanism of action; pharmacologic, pharmacokinetic, and dynamic properties; potential drug interactions; and the results of clinical trials evaluating efficacy and tolerability associated with pazopanib for the treatment of RCC...
March 2012: Clinical Therapeutics
(no author information available yet)
Renal cell carcinoma accounts for 2-3% of all adult malignancies worldwide, and around 30% of patients with the condition present with advanced or metastatic disease.1,2 Until recently, cytokine therapy (e.g. interleukin-2 or interferon-alfa) was the standard treatment for metastatic renal cell carcinoma but provided only a small survival advantage (e.g. extending life by a median of 2.5 months).3 A key development has been the introduction of drugs known as receptor tyrosine kinase inhibitors, which include ▾sunitinib (Sutent-Pfizer), ▾sorafenib (Nexavar-Bayer) and ▾pazopanib (Votrient-GlaxoSmithKline)...
November 2011: Drug and Therapeutics Bulletin
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