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Pazopanib

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https://www.readbyqxmd.com/read/27905309/an-impressive-response-to-pazopanib-in-a-patient-with-metastatic-endometrial-carcinoma
#1
M J van der Steen, Y R P de Waal, A Westermann, B Tops, W Leenders, P B Ottevanger
The incidence of endometrial carcinoma is rising and the patients with distant metastases have a poor prognosis, especially when progression of disease occurs after systemic treatment with hormonal therapy or chemotherapy. Pazopanib, a multi-targeted inhibitor of several oncogenic receptor tyrosine kinases, has been investigated in patients with chemotherapy-resistant endometrial carcinoma or patients for whom chemotherapy is contraindicated. In this report we will describe a spectacular response to pazopanib in a patient with recurrent metastatic endometrial carcinoma...
November 2016: Netherlands Journal of Medicine
https://www.readbyqxmd.com/read/27904651/sunitinib-in-the-treatment-of-metastatic-renal-cell-carcinoma
#2
REVIEW
Thomas A Schmid, Martin E Gore
Sunitinib is an oral multi-targeted tyrosine kinase inhibitor (TKI) that targets various receptors, including vascular endothelial growth factor receptors (VEGFRs). Sunitinib received approval in 2006 and became a standard treatment option in the first-line treatment of metastatic renal cell cancer (mRCC) after a phase III trial showed superiority compared with interferon alpha (IFN-α). Sunitinib has also shown activity in second-line treatment in several trials. Most of the combination trials with sunitinib with various agents have led to considerable toxicity without improving efficacy...
December 2016: Therapeutic Advances in Urology
https://www.readbyqxmd.com/read/27842541/heterogeneous-response-and-progression-patterns-reveal-phenotypic-heterogeneity-of-tyrosine-kinase-inhibitor-response-in-metastatic-renal-cell-carcinoma
#3
Shanthini M Crusz, Yen Zhi Tang, Shah-Jalal Sarker, Warner Prevoo, Irfan Kiyani, Luis Beltran, John Peters, Anju Sahdev, Axel Bex, Thomas Powles, Marco Gerlinger
BACKGROUND: Molecular intratumour heterogeneity (ITH) is common in clear cell renal carcinomas (ccRCCs). However, it remains unknown whether this is mirrored by heterogeneity of drug responses between metastases in the same patient. METHODS: We performed a retrospective central radiological analysis of patients with treatment-naïve metastatic ccRCC receiving anti-angiogenic tyrosine kinase inhibitors (TKIs) (sunitinib or pazopanib) within three similar phase II trials...
November 14, 2016: BMC Medicine
https://www.readbyqxmd.com/read/27823651/first-line-antiangiogenics-for-metastatic-renal-cell-carcinoma-a-systematic-review-and-network-meta-analysis
#4
REVIEW
Benoît Rousseau, Emmanuelle Kempf, Gaelle Desamericq, Emilie Boissier, Marie Chaubet-Houdu, Charlotte Joly, Carolina Saldana, Helene Boussion, Cindy Neuzillet, Isabelle Macquin-Mavier, Stéphane Oudard, Laurent Salomon, Alexandre de la Taille, Christophe Tournigand
BACKGROUND: Sunitinib, pazopanib, sorafenib, axitinib and bevacizumab are the five recommended antiangiogenic agents in first-line therapy for metastatic renal cell carcinoma (mRCC). Because these drugs underwent simultaneous clinical development, no direct efficacy and safety comparison was ever conducted, thus preventing optimal therapy choices. METHODS: We performed a traditional and network meta-analysis to evaluate the efficacy and safety of mRCC-recommended first-line antiangiogenic agents...
November 2016: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/27822356/efficacy-of-pazopanib-and-sunitinib-in-advanced-axial-chordoma-a-single-reference-centre-case-series
#5
Astrid Lipplaa, Sander Dijkstra, Hans Gelderblom
BACKGROUND: Chordomas are rare malignant tumours of the axial skeleton and skull base supposed to arise from cellular remnants of the notochord. These tumours have the potential to metastasize (30-40 %), usually in the later course of the disease. However, the greatest morbidity is usually a result of loco-regional recurrence with infiltration and destruction of surrounding bone and soft tissue. Patients with unresectable or metastatic chordoma are faced with a poor prognosis since cytotoxic chemotherapy or other systemic therapies have not proven their efficacy yet...
2016: Clinical Sarcoma Research
https://www.readbyqxmd.com/read/27783942/dual-targeting-of-pdgfr%C3%AE-and-fgfr1-displays-synergistic-efficacy-in-malignant-rhabdoid-tumors
#6
Jocelyn P Wong, Jason R Todd, Martina A Finetti, Frank McCarthy, Malgorzata Broncel, Simon Vyse, Maciej T Luczynski, Stephen Crosier, Karen A Ryall, Kate Holmes, Leo S Payne, Frances Daley, Patty Wai, Andrew Jenks, Barbara Tanos, Aik-Choon Tan, Rachael C Natrajan, Daniel Williamson, Paul H Huang
Subunits of the SWI/SNF chromatin remodeling complex are mutated in a significant proportion of human cancers. Malignant rhabdoid tumors (MRTs) are lethal pediatric cancers characterized by a deficiency in the SWI/SNF subunit SMARCB1. Here, we employ an integrated molecular profiling and chemical biology approach to demonstrate that the receptor tyrosine kinases (RTKs) PDGFRα and FGFR1 are coactivated in MRT cells and that dual blockade of these receptors has synergistic efficacy. Inhibitor combinations targeting both receptors and the dual inhibitor ponatinib suppress the AKT and ERK1/2 pathways leading to apoptosis...
October 25, 2016: Cell Reports
https://www.readbyqxmd.com/read/27764830/activity-of-c-met-alk-inhibitor-crizotinib-and-multi-kinase-vegf-inhibitor-pazopanib-in-metastatic-gastrointestinal-neuroectodermal-tumor-harboring-ewsr1-creb1-fusion
#7
Vivek Subbiah, Oliver Holmes, Kyle Gowen, Daniel Spritz, Behrang Amini, Wei-Lien Wang, Alexa B Schrock, Funda Meric-Bernstam, Ralph Zinner, Sarina Piha-Paul, Maria Zarzour, Julia A Elvin, Rachel L Erlich, David L Stockman, Jo-Anne Vergilio, James H Suh, Philip J Stephens, Vincent Miller, Jeffrey S Ross, Siraj M Ali
Malignant gastrointestinal neuroectodermal tumor (GNET) is an aggressive rare tumor, primarily occurring in young adults with frequent local-regional metastases and recurrence after local control. The tumor is characterized by the presence of EWSR1-ATF1 or EWSR1-CREB1 and immunohistochemical positivity for S-100 protein without melanocytic marker positivity. Due to poor responses to standard sarcoma regimens, GNET has a poor prognosis, and development of effective systemic therapy is desperately needed to treat these patients...
2016: Oncology
https://www.readbyqxmd.com/read/27754995/prognostic-role-of-the-cumulative-toxicity-in-patients-affected-by-metastatic-renal-cells-carcinoma-and-treated-with-first-line-tyrosine-kinase-inhibitors
#8
Roberto Iacovelli, Elena Verri, Maria Cossu Rocca, Gaetano Aurilio, Daniela Cullurà, Ottavio de Cobelli, Franco Nolè
Tyrosine kinase inhibitor-related toxicities have been reported to be predictive and/or prognostic factors in patients affected by metastatic renal cell carcinoma (mRCC). We aim to investigate the incidence of cumulative toxicity and its prognostic role in mRCC patients treated with sunitinib or pazopanib. mRCC patients treated with sunitinib or pazopanib at the European Institute of Oncology in Milan were reviewed for the incidence of adverse events. Cumulative toxicity was defined as the presence of more than one selected adverse event of any grade...
October 14, 2016: Anti-cancer Drugs
https://www.readbyqxmd.com/read/27751846/safety-and-efficacy-of-regorafenib-in-patients-with-advanced-soft-tissue-sarcoma-regosarc-a-randomised-double-blind-placebo-controlled-phase-2-trial
#9
Olivier Mir, Thomas Brodowicz, Antoine Italiano, Jennifer Wallet, Jean-Yves Blay, François Bertucci, Christine Chevreau, Sophie Piperno-Neumann, Emmanuelle Bompas, Sébastien Salas, Christophe Perrin, Corinne Delcambre, Bernadette Liegl-Atzwanger, Maud Toulmonde, Sarah Dumont, Isabelle Ray-Coquard, Stéphanie Clisant, Sophie Taieb, Cécile Guillemet, Maria Rios, Olivier Collard, Laurence Bozec, Didier Cupissol, Esma Saada-Bouzid, Christine Lemaignan, Wolfgang Eisterer, Nicolas Isambert, Loïc Chaigneau, Axel Le Cesne, Nicolas Penel
BACKGROUND: Regorafenib is a multikinase inhibitor with proven activity in refractory gastrointestinal stromal tumours and chemotherapy-refractory advanced colorectal cancers. We assessed this agent's efficacy and safety in patients with metastatic soft tissue sarcomas previously treated with anthracycline. METHODS: In this randomised, double-blind, phase 2 trial undertaken in France and Austria, we enrolled patients aged 18 years and older with advanced soft tissue sarcomas who had received previous doxorubicin or other anthracycline treatment...
October 14, 2016: Lancet Oncology
https://www.readbyqxmd.com/read/27749781/quantification-of-11-therapeutic-kinase-inhibitors-in-human-plasma-for-therapeutic-drug-monitoring-using-liquid-chromatography-coupled-with-tandem-mass-spectrometry
#10
Maikel Herbrink, Niels de Vries, Hilde Rosing, Alwin D R Huitema, Bastiaan Nuijen, Jan H M Schellens, Jos H Beijnen
BACKGROUND: A liquid chromatography/tandem mass spectrometry assay was developed to facilitate therapeutic drug monitoring (TDM) for 10 anticancer compounds (dasatinib, erlotinib, gefitinib, imatinib, lapatinib, nilotinib, pazopanib, sorafenib, sunitinib, and vemurafenib) and the active metabolite, N-desethyl-sunitinib. METHODS: The TDM assay is based on reversed-phase chromatography coupled with tandem mass spectrometry in the positive ion mode using multiple reaction monitoring for analyte quantification...
December 2016: Therapeutic Drug Monitoring
https://www.readbyqxmd.com/read/27747102/neoadjuvant-therapy-in-differentiated-thyroid-cancer
#11
Rajan P Dang, Daniel McFarland, Valerie H Le, Nadia Camille, Brett A Miles, Marita S Teng, Eric M Genden, Krzysztof J Misiukiewicz
Objectives. Invasion of differentiated thyroid cancer (DTC) into surrounding structures can lead to morbid procedures such as laryngectomy and tracheal resection. In these patients, there is a potential role for neoadjuvant therapy. Methods. We identified three studies involving the treatment of DTC with neoadjuvant chemotherapy: two from Slovenia and one from Japan. Results. These studies demonstrate that in selected situations, neoadjuvant chemotherapy can have a good response and allow for a more complete surgical resection, the treatment of DTC...
2016: International Journal of Surgical Oncology
https://www.readbyqxmd.com/read/27721266/a-comparison-of-drug-resistances-of-targeted-drugs-for-advanced-renal-cell-cancer-approved-by-the-food-and-drug-administration-a-meta-analysis-of-randomized-clinical-trials
#12
Ming Guo, Yunsong Cao, Jingzhe Yang, Jingfeng Zhang
PURPOSE: The purpose of this study was to conduct network meta-analysis to assess drug resistances of the Food and Drug Administration-approved drugs for advanced renal cell carcinoma. MATERIALS AND METHODS: Database searches were conducted to identify randomized controlled trials reporting results for eligible treatments. After searching for PubMed, MEDLINE, EMBASE, and ISI Web of Science, 22 studies (n = 7854 patients) were included for the comparison of drug resistance in the present meta-analysis...
October 2016: Journal of Cancer Research and Therapeutics
https://www.readbyqxmd.com/read/27721264/meta-analysis-of-therapeutic-effects-and-the-risks-of-hypertension-and-hyperglycemia-in-patients-with-renal-cell-carcinoma-who-were-receiving-antiangiogenic-drugs
#13
Lingling Chang, Ying An, Shuling Yang, Xiaosu Zhang
PURPOSE: A meta-analysis of published data was conducted to investigate the therapeutic effects in patients with renal cell carcinoma (RCC) who were receiving antiangiogenic drugs. METHODS: A computerized search through electronic databases, including PubMed (until February 2016), was performed to obtain eligible randomized controlled trials that compared the effectiveness of antiangiogenic with control groups (everolimus, placebo, and interferon [IFN] alfa) in patients with RCC...
October 2016: Journal of Cancer Research and Therapeutics
https://www.readbyqxmd.com/read/27699042/simultaneous-occurrence-of-non-hodgkin-lymphoma-renal-cell-carcinoma-and-oncocytoma-a-case-report
#14
Ewa Zabrocka, Ewa Sierko, Stefan Jelski, Marek Z Wojtukiewicz
We herein report the case of a 74 year-old woman with a diffuse large B-cell lymphoma and bilateral renal masses identified on computed tomography scans during the initial staging process. Following partial bilateral nephrectomy, histopathological examination revealed renal cell carcinoma (RCC) and oncocytoma in the left and the right kidneys, respectively. Shortly afterwards, lymphoma of the left palatine tonsil was diagnosed and the patient received chemotherapy with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP regimen), followed by radiotherapy...
October 2016: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/27664394/improvement-in-survival-end-points-of-patients-with-metastatic-renal-cell-carcinoma-through-sequential-targeted-therapy
#15
Emiliano Calvo, Manuela Schmidinger, Daniel Y C Heng, Viktor Grünwald, Bernard Escudier
Survival of patients with metastatic renal cell carcinoma (mRCC) has improved since the advent of targeted therapy. Approved agents include the multi-targeted tyrosine kinase inhibitors (TKIs) sunitinib, sorafenib, axitinib, pazopanib, cabozantinib, and lenvatinib (approved in combination with everolimus), the anti-VEGF monoclonal antibody bevacizumab, the mammalian target of rapamycin (mTOR) inhibitors everolimus and temsirolimus, and the programmed death-1 (PD-1) targeted immune checkpoint inhibitor nivolumab...
September 10, 2016: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/27663599/pharmacokinetically-guided-dosing-of-oral-drugs-true-precision-oncology
#16
Moshe C Ornstein, Brian I Rini
Higher plasma concentrations of tyrosine kinase inhibitors (TKI), such as pazopanib, are associated with improved clinical outcomes. However, TKI pharmacokinetics exhibit significant interpatient variability, resulting in inconsistent and unpredictable plasma drug levels. An individualized dosing approach based on patient pharmacokinetics data and toxicity can potentially optimize plasma concentrations of pazopanib. Clin Cancer Res; 22(23); 5626-8. ©2016 AACRSee related article by Verheijen et al., p. 5738...
December 1, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27663525/risk-factors-for-pneumothorax-in-advanced-and-or-metastatic-soft-tissue-sarcoma-patients-during-pazopanib-treatment-a-single-institute-analysis
#17
Kenji Nakano, Noriko Motoi, Junichi Tomomatsu, Tabu Gokita, Keisuke Ae, Taisuke Tanizawa, Seiichi Matsumoto, Shunji Takahashi
BACKGROUND: After the approval of pazopanib for the treatment of soft tissue sarcoma (STS), pneumothorax was reported as an unexpected adverse event during pazopanib treatment. The incidence and risk factors of pneumothorax during pazopanib treatment for STSs have not been established yet. METHODS: We retrospectively reviewed the cases of all of the STS patients treated with pazopanib between November 2012 and December 2014 at our institute and evaluated the prevalence, incidence, treatment details and risk factors for pneumothorax in the STS patients during pazopanib treatment...
2016: BMC Cancer
https://www.readbyqxmd.com/read/27647404/-relationship-between-treatment-related-hypertension-and-therapeutic-efficacy-of-vascular-endothelial-growth-factor-receptor-tyrosine-kinase-inhibitors-in-metastatic-renal-cell-carcinoma
#18
Y Song, C X Du, W Zhang, Y K Sun, L Yang, C X Cui, Yihebali Chi, A P Zhou, J W Wang, Y Sun
OBJECTIVE: Vascular endothelial growth factor receptor-tyrosine kinase inhibitors (VEGFR-TKIs) are widely used for the treatment of metastatic renal cell carcinoma (mRCC). The aim of this study was to investigate the association between treatment-related hypertension and the therapeutic efficacy of VEGFR-TKIs. METHODS: Clinical data of 155 mRCC patients treated with VEGFR-TKIs at the Cancer Hospital of Chinese Academy of Medical Sciences from 2006 to 2014 were retrospectively analyzed...
September 23, 2016: Zhonghua Zhong Liu za Zhi [Chinese Journal of Oncology]
https://www.readbyqxmd.com/read/27647230/response-to-pazopanib-in-two-pediatric-patients-with-pretreated-relapsing-synovial-sarcoma
#19
Michela Casanova, Eleonora Basso, Chiara Magni, Luca Bergamaschi, Stefano Chiaravalli, Roberto Carta, Elisa Tirtei, Maura Massimino, Franca Fagioli, Andrea Ferrari
Pazopanib is an oral multikinase inhibitor that has proved effective in adults treated for relapsing soft tissue sarcoma and synovial sarcoma in particular. Two cases are reported here of pediatric patients with pretreated relapsing synovial sarcoma whose tumors showed a prolonged response to pazopanib given on compassionate grounds. These results suggest that new agents found effective in adult patients might achieve similar results in adolescents with the same disease. Facilitating the availability of new drugs for children and adolescents is a major challenge for pediatric oncologists...
August 25, 2016: Tumori
https://www.readbyqxmd.com/read/27634566/dynamic-contrast-enhanced-magnetic-resonance-imaging-as-a-pharmacodynamic-biomarker-for-pazopanib-in-metastatic-renal-carcinoma
#20
Randy F Sweis, Milica Medved, Shannon Towey, Gregory S Karczmar, Aytekin Oto, Russell Z Szmulewitz, Peter H O'Donnell, Paul Fishkin, Theodore Karrison, Walter M Stadler
INTRODUCTION/BACKGROUND: Traditional imaging assessment criteria might not correlate well with clinical benefit from vascular endothelial growth factor pathway-directed therapy in metastatic renal cancer. Preclinical data suggest tumor growth is preceded by a rise in K(trans) level, a parameter derived from dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) that reflects vascular permeability. We thus hypothesized that K(trans) might be a predictive biomarker for pazopanib...
August 17, 2016: Clinical Genitourinary Cancer
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