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Pazopanib renal

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https://www.readbyqxmd.com/read/28983380/acute-pancreatitis-related-to-a-chemotherapy-drug
#1
Ghulam Murtaza, Anadil Faqah, Nicholas Konowitz, Hannah Lu, Aneesh Kuruvilla, Sujeen Adhikari
Drug-induced acute pancreatitis is a rare cause of pancreatitis. We present a case of pancreatitis caused by pazopanib, a tyrosine kinase inhibitor used in the treatment of renal cell carcinoma. A 57-year-old male with no risk factors for pancreatitis and a past medical history of renal cell carcinoma who was being treated with pazopanib presented with epigastric pain with radiation to the back. Lipase was elevated to 7,960 units/L. Pazopanib was discontinued on arrival and his lipase levels decreased from 7,960 to 3,380 units/L one day after discontinuation...
February 2017: World Journal of Oncology
https://www.readbyqxmd.com/read/28950297/a-randomized-phase-2-trial-of-crlx101-in-combination-with-bevacizumab-versus-standard-of-care-in-patients-with-advanced-renal-cell-carcinoma
#2
M H Voss, A Hussain, N Vogelzang, J L Lee, B Keam, S Y Rha, U Vaishampayan, W B Harris, S Richey, J M Randall, D Shaffer, A Cohn, T Crowell, J Li, A Senderowicz, E Stone, R Figlin, R J Motzer, N B Haas, T Hutson
Background: Nanoparticle-drug conjugates (NDC) enhance drug delivery to tumors. Gradual payload release inside cancer cells augments antitumor activity while reducing toxicity. CRLX101 is a novel NDC containing camptothecin a potent inhibitor of topoisomerase I and the hypoxia-inducible factors (HIF) 1α and 2α. In a phase 1b/2 trial, CRLX101+bevacizumab was well tolerated with encouraging activity in metastatic renal cell carcinoma (mRCC). We conducted a randomized phase 2 trial comparing CRLX101+bevacizumab versus standard of care (SOC) in refractory mRCC...
September 11, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28938918/combined-high-dose-radiation-and-pazopanib-in-metastatic-renal-cell-carcinoma-a-phase-i-dose-escalation-trial
#3
Katrien De Wolf, Sylvie Rottey, Karim Vermaelen, Karel Decaestecker, Nora Sundahl, Lizzy De Lobel, Els Goetghebeur, Gert De Meerleer, Nicolaas Lumen, Valérie Fonteyne, Daan De Maeseneer, Piet Ost
BACKGROUND: The primary objective was to determine maximum tolerated radiation dose in patients with metastatic renal cell carcinoma on pazopanib treatment. METHODS: Treatment-naïve patients received pazopanib according to standard of care. Stereotactic body radiotherapy (SBRT) was delivered concurrently to the largest metastatic lesion at day 8, 10 and 12. SBRT doses were escalated in 3 dose levels (24 Gy/3, 30 Gy/3 and 36 Gy/3). Dose level was assigned using Time-to-Event Continual Reassessment Method with the target dose-limiting toxicity rate set to 0...
September 22, 2017: Radiation Oncology
https://www.readbyqxmd.com/read/28903416/overriding-tki-resistance-of-renal-cell-carcinoma-by-combination-therapy-with-il-6-receptor-blockade
#4
Kei Ishibashi, Tobias Haber, Ines Breuksch, Susanne Gebhard, Takashi Sugino, Hitoshi Kubo, Junya Hata, Tomoyuki Koguchi, Michihiro Yabe, Masao Kataoka, Soichiro Ogawa, Hiroyuki Hiraki, Tomohiko Yanagida, Nobuhiro Haga, Joachim W Thüroff, Dirk Prawitt, Walburgis Brenner, Yoshiyuki Kojima
Metastatic renal cell carcinoma (RCC) is a tumor entity with poor prognosis due to limited therapy options. Tyrosine kinase inhibitors (TKI) represent the standard of care for RCCs, however a significant proportion of RCC patients develop resistance to this therapy. Interleukin-6 (IL-6) is considered to be associated with poor prognosis in RCCs. We therefore hypothesized that TKI resistance and IL-6 secretion are causally connected. We first analyzed IL-6 expression after TKI treatment in RCC cells and RCC tumor specimens...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28902533/randomized-phase-iii-trial-of-adjuvant-pazopanib-versus-placebo-after-nephrectomy-in-patients-with-localized-or-locally-advanced-renal-cell-carcinoma
#5
Robert J Motzer, Naomi B Haas, Frede Donskov, Marine Gross-Goupil, Sergei Varlamov, Evgeny Kopyltsov, Jae Lyun Lee, Bohuslav Melichar, Brian I Rini, Toni K Choueiri, Milada Zemanova, Lori A Wood, M Neil Reaume, Arnulf Stenzl, Simon Chowdhury, Ho Yeong Lim, Ray McDermott, Agnieszka Michael, Weichao Bao, Marlene J Carrasco-Alfonso, Paola Aimone, Maurizio Voi, Christian Doehn, Paul Russo, Cora N Sternberg
Purpose This phase III trial evaluated the efficacy and safety of pazopanib versus placebo in patients with locally advanced renal cell carcinoma (RCC) at high risk for relapse after nephrectomy. Patients and Methods A total of 1,538 patients with resected pT2 (high grade) or ≥ pT3, including N1, clear cell RCC were randomly assigned to pazopanib or placebo for 1 year; 403 patients received a starting dose of 800 mg or placebo. To address toxicity attrition, the 800-mg starting dose was lowered to 600 mg, and the primary end point analysis was changed to disease-free survival (DFS) for pazopanib 600 mg versus placebo (n = 1,135)...
September 13, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28891933/tyrosine-kinase-inhibitors-therapies-with-mainly-anti-angiogenic-activity-in-advanced-renal-cell-carcinoma-value-of-pet-ct-in-response-evaluation
#6
REVIEW
Girolamo Ranieri, Ilaria Marech, Artor Niccoli Asabella, Alessandra Di Palo, Mariangela Porcelli, Valentina Lavelli, Giuseppe Rubini, Cristina Ferrari, Cosmo Damiano Gadaleta
Renal cell carcinoma (RCC) is the most frequent renal tumor and the majority of patients are diagnosed with advanced disease. Tumor angiogenesis plays a crucial role in the development and progression of RCC together with hypoxia and glucose metabolism. These three pathways are strictly connected to the cell growth and proliferation, like a loop that is self-feeding. Over the last few years, the ever-deeper knowledge of its contribution in metastatic RCC led to the discovery of numerous tyrosine kinase inhibitors (TKIs) targeting pro-angiogenic receptors at different levels such as sunitinib, sorafenib, pazopanib, axitinib, tivozanib, and dovitinib...
September 9, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28810837/phase-i-dose-escalation-study-of-pazopanib-combined-with-bevacizumab-in-patients-with-metastatic-renal-cell-carcinoma-or-other-advanced-tumors
#7
Sylvie Négrier, David Pérol, Rastislav Bahleda, Antoine Hollebecque, Etienne Chatelut, Helen Boyle, Philippe Cassier, Séverine Metzger, Ellen Blanc, Jean-Charles Soria, Bernard Escudier
BACKGROUND: Vascular endothelial growth factor (VEGF) directed therapies are being used in a large number of advanced tumors. Metastatic renal cell carcinoma (mRCC) is highly dependent on the VEGF pathway; VEGF receptor (VEGFR) tyrosine kinase inhibitors (TKI) and humanized VEGF monoclonal antibody have been registered for clinical use in advanced renal cell carcinoma. The VEGFR TKI, pazopanib, with a rather manageable toxicity profile, was preferred to sunitinib by mRCC patients. We investigate the combination of pazopanib and bevacizumab to determine the maximum tolerated dose (MTD) in mRCC and other advanced solid tumors...
August 15, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28801802/does-dose-modification-affect-efficacy-of-first-line-pazopanib-in-metastatic-renal-cell-carcinoma
#8
Paolo Grassi, Elena Verzoni, Raffaele Ratta, Luca Porcu, Michele Prisciandaro, Alessia Mennitto, Giuseppina Calareso, Filippo de Braud, Giuseppe Procopio
BACKGROUND: Pazopanib is a standard treatment for metastatic renal cell carcinoma (mRCC), and 800 mg/daily is considered the optimal dose. However, some patients require dose modification because of toxicity. Whether a reduced dose of pazopanib is as effective as the standard dose in achieving clinical benefit remains unclear. OBJECTIVES: Our objective was to conduct a retrospective analysis to investigate the clinical effect of different therapeutic doses of first-line pazopanib in patients with mRCC...
August 11, 2017: Drugs in R&D
https://www.readbyqxmd.com/read/28761748/new-treatment-options-for-metastatic-renal-cell-carcinoma
#9
REVIEW
Alejo Rodriguez-Vida, Thomas E Hutson, Joaquim Bellmunt, Michiel H Strijbos
During the last decade, the treatment of advanced or metastatic renal cell carcinoma (RCC) was revolutionised with the advent of antiangiogenic drugs and tyrosine-kinase inhibitors. Several agents targeting the vascular endothelial growth factor (VEGF) pathway (sunitinib, bevacizumab, pazopanib, axitinib) or the mammalian target of rapamycin pathway (temsirolimus, everolimus) were since then progressively approved for first-line or later-line use in the treatment of patients with advanced RCC and became the new standard of care...
2017: ESMO Open
https://www.readbyqxmd.com/read/28753585/overriding-tki-resistance-of-renal-cell-carcinoma-by-combination-therapy-with-il-6-receptor-blockade
#10
Kei Ishibashi, Tobias Haber, Ines Breuksch, Susanne Gebhard, Takashi Sugino, Hitoshi Kubo, Junya Hata, Tomoyuki Koguchi, Michihiro Yabe, Masao Kataoka, Soichiro Ogawa, Hiroyuki Hiraki, Tomohiko Yanagida, Nobuhiro Haga, Joachim W Thüroff, Dirk Prawitt, Walburgis Brenner, Yoshiyuki Kojima
Metastatic renal cell carcinoma (RCC) is a tumor entity with poor prognosis due to limited therapy options. Tyrosine kinase inhibitors (TKI) represent the standard of care for RCCs, however a significant proportion of RCC patients develop resistance to this therapy. Interleukin-6 (IL-6) is considered to be associated with poor prognosis in RCCs. We therefore hypothesized that TKI resistance and IL-6 secretion are causally connected. We first analyzed IL-6 expression after TKI treatment in RCC cells and RCC tumor specimens...
July 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28748721/real-world-costs-and-outcomes-in-metastatic-renal-cell-carcinoma-patients-treated-with-targeted-therapies-a-cohort-study-from-the-french-health-insurance-database
#11
Rana Maroun, Laetitia Fleury, Gaelle Nachbaur, Franck Maunoury, Jean-Louis Vanhille, Isabelle Durand-Zaleski
OBJECTIVES: The objective of this study was to describe treatment patterns, survival, healthcare use and costs in patients with metastatic renal cell carcinoma (mRCC) in a real-world setting. RESEARCH DESIGN AND METHODS: We used the National Health Insurance (NHI) claims database for the Ile-de-France region to perform a retrospective cohort analysis of patients with mRCC treated by a first-line targeted therapy. Treatment naïve patients were identified combining the 10th revision of the International Classification of Diseases (ICD-10) codes (C64 & C77-C79) and a first prescription of targeted therapies...
August 7, 2017: Current Medical Research and Opinion
https://www.readbyqxmd.com/read/28748331/eligibility-for-phase-3-clinical-trials-of-systemic-therapy-in-real-world-patients-with-metastatic-renal-cell-cancer-managed-in-a-rural-region
#12
Carsten Nieder, Mohsan A Syed, Astrid Dalhaug, Adam Pawinski, Jan Norum
Previous research has identified disparities between urban and rural cancer care, including clinical trial access. Therefore, we addressed three different questions in patients with metastatic renal cell cancer managed according to national guidelines in a rural Norwegian standard practice setting. (1) How many patients would have been eligible for three recent landmark randomized clinical trials? (2) Is survival different between eligible and non-eligible patients receiving first-line systemic therapy? (3) Is survival different between eligible patients and published trial results? We performed a retrospective analysis of 101 consecutive patients (2006-2016)...
September 2017: Medical Oncology
https://www.readbyqxmd.com/read/28732453/real-world-chart-review-study-of-adverse-events-management-in-patients-taking-tyrosine-kinase-inhibitors-to-treat-metastatic-renal-cell-carcinoma
#13
Sandy Srinivas, Dara Stein, Dana Y Teltsch, Sunning Tao, Laura Cisar, Krishnan Ramaswamy
Purpose The purpose is to describe management of adverse events of special interest across tyrosine kinase inhibitors approved for metastatic renal cell carcinoma. Methods We conducted a retrospective chart review in metastatic renal cell carcinoma patients initiating tyrosine kinase inhibitor monotherapy between 15 November 2010 and 15 November 2013, and experiencing ≥ 1 adverse events of special interest (diarrhea, fatigue, hand-foot syndrome, hypertension, or stomatitis/mucositis) within 3 months of initiation...
January 1, 2017: Journal of Oncology Pharmacy Practice
https://www.readbyqxmd.com/read/28731496/prognostic-factors-for-survival-in-metastatic-renal-cell-carcinoma-patients-with-brain-metastases-receiving-targeted-therapy
#14
Ibrahim Yildiz, Ahmet Bilici, Nuri Karadurmuş, Leyla Ozer, Deniz Tural, Mehmet A Kaplan, Tülay Akman, Ibrahim V Bayoglu, Mükremin Uysal, Yaşar Yildiz, Özgür Tanriverdi, Ozan Yazici, Zeki Sürmeli, Nazim Serdar Turhal, Sevil Bavbek, Fatih Selçukbiricik, Doğan Koca, Mert Basaran
BACKGROUND: The primary objective of our study was to examine the clinical outcomes and prognosis of patients with metastatic renal cell carcinoma (mRCC) with brain metastases (BMs) receiving targeted therapy. PATIENTS AND METHODS: Fifty-eight patients from 16 oncology centers for whom complete clinical data were available were retrospectively reviewed. RESULTS: The median age was 57 years (range 30-80). Most patients underwent a nephrectomy (n = 41; 70...
July 14, 2017: Tumori
https://www.readbyqxmd.com/read/28683470/integrating-cytokines-and-angiogenic-factors-and-tumour-bulk-with-selected-clinical-criteria-improves-determination-of-prognosis-in-advanced-renal-cell-carcinoma
#15
A J Zurita, R C Gagnon, Y Liu, H T Tran, R A Figlin, T E Hutson, A M D'Amelio, C N Sternberg, L N Pandite, J V Heymach
BACKGROUND: In two clinical trials of the vascular endothelial growth factor (VEGF) receptor inhibitor pazopanib in advanced renal cell carcinoma (mRCC), we found interleukin-6 as predictive of pazopanib benefit. We evaluated the prognostic significance of candidate cytokines and angiogenic factors (CAFs) identified in that work relative to accepted clinical parameters. METHODS: Seven preselected plasma CAFs (interleukin-6, interleukin-8, osteopontin, VEGF, hepatocyte growth factor, tissue inhibitor of metalloproteinases (TIMP-1), and E-selectin) were measured using multiplex ELISA in plasma collected pretreatment from 343 mRCC patients participating in the phase 3 registration trial of pazopanib vs placebo (NCT00334282)...
August 8, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28680399/pazopanib-in-patients-with-clear-cell-renal-cell-carcinoma-seeking-the-right-patient
#16
Camillo Porta, Alessandra Ferrari, Anna M Czarnecka, Cezary A Szczylik
No abstract text is available yet for this article.
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28679190/metastasis-of-renal-cell-carcinoma-to-the-thyroid-gland-9-years-after-nephrectomy-a-case-report-and-literature-review
#17
Zeki Bayraktar, Selami Albayrak
We report a case presenting with thyroid and lung metastases of renal cell carcinoma that was treated with molecular targeted therapy followed metastasectomy. A 52-year-old female underwent radical nephrectomy of right renal cell carcinoma in 2007. The patient presented 9 years after nephrectomy at the age of 61 years with sudden loss of vision on the left side and a mass on the neck. On magnetic resonance imagining, there was a mass on the midline of the neck, extending to the left, measuring 46 x 31 mm and containing central cystic-necrotic areas...
June 30, 2017: Archivio Italiano di Urologia, Andrologia
https://www.readbyqxmd.com/read/28664385/pazopanib-a-review-in-advanced-renal-cell-carcinoma
#18
REVIEW
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
https://www.readbyqxmd.com/read/28636648/cost-effectiveness-of-pazopanib-versus-sunitinib-for-metastatic-renal-cell-carcinoma-in-the-united-kingdom
#19
COMPARATIVE STUDY
Jordan Amdahl, Jose Diaz, Arati Sharma, Jinhee Park, David Chandiwana, Thomas E Delea
BACKGROUND: Sunitinib and pazopanib are the only two targeted therapies for the first-line treatment of locally advanced or metastatic renal cell carcinoma (mRCC) recommended by the United Kingdom's National Institute for Health and Care Excellence. Pazopanib demonstrated non-inferior efficacy and a differentiated safety profile versus sunitinib in the phase III COMPARZ trial. The current analysis provides a direct comparison of the cost-effectiveness of pazopanib versus sunitinib from the perspective of the United Kingdom's National Health Service based on data from COMPARZ and other sources...
2017: PloS One
https://www.readbyqxmd.com/read/28590313/current-management-of-metastatic-renal-cell-carcinoma-evolving-new-therapies
#20
Ravi Kumar, Anil Kapoor
PURPOSE OF REVIEW: Targeted therapies have recently replaced cytokine treatments as the gold standard for management of metastatic renal cell carcinoma (mRCC). Currently approved treatments include the tyrosine kinase inhibitors sunitinib, pazopanib, axitinib, sorafenib, cabozantinib and lenvatinib; the vascular endothelial growth factor (VEGF) inhibitor bevacizumab; the mammalian target of rapamycin (mTOR) inhibitors everolimus and temsirolimus; and the immunologic nivolumab. The purpose of this review is to provide an updated analysis of the clinical data supporting the use of these agents in the first-line and second-line setting...
September 2017: Current Opinion in Supportive and Palliative Care
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