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cabozantinib kidney

Steven S Yu, David I Quinn, Tanya B Dorff
Clear cell (cc) renal cell carcinoma (RCC) is the most common type of cancer found in the kidney accounting for ~90% of all kidney cancers. In 2012, there were ~337,000 new cases of RCC diagnosed worldwide with an estimated 143,000 deaths, with the highest incidence and mortality in Western countries. Despite improvements in cancer control achieved with VEGF- and mTOR-targeted therapy for RCC, progression remains virtually universal and additional therapies are needed. The pivotal results of the METEOR trial led to cabozantinib's designation as a breakthrough drug by the US Food and Drug Administration and its approval for treatment of advanced RCC in 2016...
2016: OncoTargets and Therapy
Sebastiano Buti, Alessandro Leonetti, Alice Dallatomasina, Melissa Bersanelli
INTRODUCTION: Renal cell carcinoma (RCC) is the most common type of kidney cancer in adults, and its pathogenesis is strictly related to altered cellular response to hypoxia, in which mTOR signaling pathway is implicated. Everolimus, an mTOR serine/threonine kinase inhibitor, represents a therapeutic option for the treatment of advanced RCC. AIM: The objective of this article is to review the evidence for the treatment of metastatic RCC with everolimus. EVIDENCE REVIEW: Everolimus was approved for second- and third-line therapy in patients with advanced RCC according to the results of a Phase III pivotal trial that demonstrated a benefit in median progression-free survival of ~2 months compared to placebo after failure of previous lines of therapy, of which at least one was an anti-VEGFR tyrosine kinase inhibitor (TKI)...
2016: Core Evidence
Karim Fizazi
The last 2 years (2014 and 2015) have witnessed major advances in the treatment of genitourinary malignancies. Of note and in marked contrast to previous years, all four major cancers (prostate cancer, testicular cancer, kidney cancer, and bladder cancer) have benefited from this progress. In prostate cancer, it was clearly demonstrated that a local treatment should be administered for high-risk localised disease. The standard of care was changed for patients with upfront metastatic disease with combined androgen deprivation therapy plus docetaxel becoming the new standard for fit patients with multiple bony metastases...
October 2016: European Journal of Cancer
Zuoquan Xie, Young H Lee, Marta Boeke, Lucia B Jilaveanu, Zongzhi Liu, Donald P Bottaro, Harriet M Kluger, Brian Shuch
BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is the most lethal form of kidney cancer. Small molecule VEGFR inhibitors are widely used but are not curative and various resistance mechanisms such as activation of the MET pathway have been described. Dual MET/VEGFR2 inhibitors have recently shown clinical benefit but limited preclinical data evaluates their effects in ccRCC. METHODS: An interrogation of the Cancer Genome Atlas (TCGA) dataset was performed to evaluate oncogenic alterations in the MET/VEGFR2 pathway...
2016: Journal of Cancer
Ulka N Vaishampayan
Although two phase III trials support the recommendation of nephrectomy followed by interferon alpha in metastatic renal cell carcinoma (RCC), this procedure cannot be applied to every patient with this condition. Systemic therapy has changed from interferon alpha to antiangiogenic-targeted therapy, and the clinical impact of nephrectomy in the era of targeted therapy has not been proven. The SEER database shows that only 35% of patients with advanced RCC undergo nephrectomy as their initial treatment. Retrospective studies showed improved overall survival (OS) outcomes with nephrectomy and interleukin-2 (IL-2) therapy; however, the inherent selection bias of younger and healthier patients receiving IL-2 likely accounts for this finding...
2016: American Society of Clinical Oncology Educational Book
Clément Bonnet, Guillaume Beinse, Luc Cabel, Delphine Cochereau, Pernelle Lavaud, Pauline Rochefort, Emeline Tabouret, Anthony Turpin, Loic Verlingue, Cécile Vicier, Christophe Massard
The ESMO/ECC congress (European Society for Medical Oncology/European Cancer Congress) took place in Vienna, Austria, September 25-29. The main topic of the conference was immunotherapies especially in advanced kidney cancer with nivolumab in phase III and in metastatic lung cancer with atezolizumab in phase II. Targeted therapies were also highlighted with cabozantinib proposed in advanced renal cancer or everolimus in differenciated neuroendocrine tumors grade 1 or 2. Furthermore the current challenges remain unchanged: improving patients' care through better selection and finding biomarkers using simple samples (blood or urine)...
June 2016: Bulletin du Cancer
Luke Worley
No abstract text is available yet for this article.
November 2015: Lancet Oncology
Clemens Thoma
No abstract text is available yet for this article.
November 2015: Nature Reviews. Clinical Oncology
Clemens Thoma
No abstract text is available yet for this article.
December 2015: Nature Reviews. Urology
Toni K Choueiri, Bernard Escudier, Thomas Powles, Paul N Mainwaring, Brian I Rini, Frede Donskov, Hans Hammers, Thomas E Hutson, Jae-Lyun Lee, Katriina Peltola, Bruce J Roth, Georg A Bjarnason, Lajos Géczi, Bhumsuk Keam, Pablo Maroto, Daniel Y C Heng, Manuela Schmidinger, Philip W Kantoff, Anne Borgman-Hagey, Colin Hessel, Christian Scheffold, Gisela M Schwab, Nizar M Tannir, Robert J Motzer
BACKGROUND: Cabozantinib is an oral, small-molecule tyrosine kinase inhibitor that targets vascular endothelial growth factor receptor (VEGFR) as well as MET and AXL, each of which has been implicated in the pathobiology of metastatic renal-cell carcinoma or in the development of resistance to antiangiogenic drugs. This randomized, open-label, phase 3 trial evaluated the efficacy of cabozantinib, as compared with everolimus, in patients with renal-cell carcinoma that had progressed after VEGFR-targeted therapy...
November 5, 2015: New England Journal of Medicine
Xianqin Wang, Shuanghu Wang, Feiyan Lin, Qingwei Zhang, HuiLing Chen, Xianchuan Wang, Congcong Wen, Jianshe Ma, Lufeng Hu
Cabozantinib (XL184) is a novel small molecule inhibitor of receptor tyrosine kinases (RTKs) targeted at mesenchymal-epithelial transition factor (MET). In order to study the pharmacokinetics and tissue distribution in rat, a specific ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed with midazolam as internal standard. The calibration curves in plasma and tissues were linear in the range of 5-5000ng/mL (r(2)>0.99). The recoveries were better than 80.4% and matrix effects ranged from 96...
March 1, 2015: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
George K Philips, Michael B Atkins
The vascular endothelial growth factor (VEGF) pathway blockers and mammalian target of rapamycin (mTOR) inhibitors have dramatically improved the treatment options and outcome for patients with advanced renal cell carcinoma (RCC). However, because the vast majority of patients will still succumb to their disease, novel treatment approaches are still necessary. Efforts to identify novel therapeutic target treatments are focused on better understanding unique aspects of tumor cell biology guided the Cancer Genome Atlas analyses and the interaction of the tumor with its microenvironment...
2014: American Society of Clinical Oncology Educational Book
T K Choueiri, S K Pal, D F McDermott, S Morrissey, K C Ferguson, J Holland, W G Kaelin, J P Dutcher
BACKGROUND: Cabozantinib targets tyrosine kinases including the hepatocyte growth factor receptor (MET) and vascular endothelial growth factor (VEGF) receptor 2, which are important drug targets in renal cell carcinoma (RCC). PATIENTS AND METHODS: This single-arm open-label phase I trial evaluated the safety and tolerability of cabozantinib in heavily pretreated patients with metastatic clear cell RCC. RESULTS: The study enrolled 25 RCC patients for whom standard therapy had failed...
August 2014: Annals of Oncology: Official Journal of the European Society for Medical Oncology
Joaquim Bellmunt, Francesc Pons, Abigail Foreshew, André P Fay, Thomas Powles, Camillo Porta, Sergio Bracarda, Megan E Lampron, Linda Cerbone, Cora N Sternberg, Thomas E Hutson, Toni K Choueiri
INTRODUCTION/BACKGROUND: Patients with metastatic renal cell carcinoma (mRCC) in whom first-line therapies have failed might derive clinical benefit with sequential targeted agents. Limited data are available on the efficacy and toxicity of subsequent therapies after disease progression during pazopanib therapy. PATIENTS AND METHODS: Patients with mRCC who received subsequent systemic treatment after pazopanib treatment failure were identified across 7 institutions...
August 2014: Clinical Genitourinary Cancer
Tanya B Dorff, Sumanta K Pal, David I Quinn
Although targeted therapy against VEGF and mTOR have revolutionized the treatment of advanced renal cell carcinoma (RCC), additional agents are required due to toxicity and resistance to currently available drugs. Some next-generation tyrosine kinase inhibitors have focused on VEGF, narrowing the spectrum of receptors which are inhibited and enhancing binding affinity. However, targeting novel receptors with tyrosine kinase inhibition of additional receptor targets has also emerged as an important future therapeutic strategy for RCC, both clear cell and variant histology...
January 2014: Expert Review of Clinical Pharmacology
Viktor Grünwald, Axel Stuart Merseburger
The field of renal cell carcinoma (RCC) treatment has changed dramatically during recent years. Sunitinib, sorafenib and pazopanib were the first generation of vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKIs) to have significant clinical activity in metastatic clear cell RCC. These TKI share inhibition of VEGFR family members, but differ in their ability to block other cellular kinases. Axitinib and tivozanib are 2nd generation TKIs, which show high specificity for VEGFR inhibition and exert a favourable toxicity profile...
July 2013: European Journal of Cancer
Ulka Vaishampayan
Cabozantinib/XL184 (Exelexis, Inc.) has demonstrated remarkable responses in kidney cancer. Preclinical results revealed VEGF, KIT and MET inhibition in a variety of solid tumors such as thyroid, ovarian, renal, lung, liver and prostate cancers. A phase II trial demonstrated efficacy in renal cancer with a 28 % objective response rate, stable disease rate of 62 % and median progression free survival of 14.7 months. Predominant toxicities of fatigue and diarrhea were noted. Dramatic responses in bone metastases (three of four patients) make the agent especially valuable for palliation in a disease, where presence of bone metastases is a predictor of worse survival...
April 2013: Current Oncology Reports
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