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Pazopanib and renal cell carcinoma

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https://www.readbyqxmd.com/read/29330204/pazopanib-exposure-relationship-with-clinical-efficacy-and-safety-in-the-adjuvant-treatment-of-advanced-renal-cell-carcinoma
#1
Cora Sternberg, Frede Donskov, Naomi B Haas, Christian Doehn, Paul Russo, Mohamed A Elmeliegy, Guillaume Baneyx, Hiya Banerjee, Paola Aimone, Robert J Motzer
PURPOSE: PROTECT, a phase III randomized placebo-controlled study, evaluated pazopanib efficacy and safety in the adjuvant RCC setting. The relationship between pazopanib exposure (Ctrough) and efficacy and safety was evaluated. EXPERIMENTAL DESIGN: Evaluable steady-state blood trough concentrations were collected from 311 patients at week 3 or 5 (early Ctrough), and 250 patients at week 16 or 20 (late Ctrough). Pazopanib pharmacokinetic (PK) data was analyzed via a population model approach...
January 12, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29329663/reintroducing-pazopanib-reverses-the-primary-resistance-of-nivolumab-in-a-patient-with-metastatic-clear-cell-renal-cell-carcinoma
#2
Harvey Yu-Li Su
No abstract text is available yet for this article.
December 21, 2017: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/29311252/pazopanib-induced-hypertension-in-patients-with-renal-cell-carcinoma-is-associated-with-low-urine-excretion-of-no-metabolites
#3
Anne Robdrup Tinning, Camilla Bengtsen, Niels Viggo Jensen, Lars Bastholt, Boye Lagerbon Jensen, Kirsten Madsen
Drugs targeting VEGF (vascular endothelial growth factor) are often associated with rapid development of hypertension by a yet not fully understood mechanism. VEGF is expressed in renal epithelial cells and stimulates NO production. In the renal medulla, inhibition of NO formation by local L-NAME or by impaired endothelin-1 leads to hypertension. The present study was designed to test the hypothesis that VEGF receptor inhibitor treatment leads to hypertension through decreased renal medullary formation of NO and endothelin-1...
January 8, 2018: Hypertension
https://www.readbyqxmd.com/read/29283445/simultaneous-analysis-of-oral-anticancer-drugs-for-renal-cell-carcinoma-in-human-plasma-using-liquid-chromatography-electrospray-ionization-tandem-mass-spectrometry
#4
Shinya Takasaki, Masaki Tanaka, Masafumi Kikuchi, Masamitsu Maekawa, Yoshihide Kawasaki, Akihiro Ito, Yoichi Arai, Hiroaki Yamaguchi, Nariyasu Mano
An analytical method using high performance liquid chromatography/electrospray ionization tandem mass spectrometry has been developed and validated for simultaneous measurement of four tyrosine kinase inhibitors used for renal cell carcinoma and their metabolites in human plasma. Despite their similar structures, it is difficult to measure plasma levels of these compounds simultaneously using optimal MS parameters for each compound because a quantitative range exceeding 50,000-fold is required. To overcome this problem, we used a linear range shift technique using in-source collision-induced dissociation...
December 28, 2017: Biomedical Chromatography: BMC
https://www.readbyqxmd.com/read/29279698/pazopanib-and-statin-induced-rhabdomyolysis
#5
Jennifer M Logue, Bahram Kiani, Rhonda L Bitting
Background: The VEGF inhibitor pazopanib is a widely used first-line therapy for the treatment of advanced renal cell carcinoma. Potential drug-drug interactions and toxicities may be underrecognized. Case Presentation: A 73-year-old woman with metastatic renal cell carcinoma on treatment with pazopanib presented with progressive inability to ambulate. The initial concern was for metastasis to the spine. However, MRI of the spine revealed diffuse muscle edema with no metastatic deposits or lytic lesions...
September 2017: Case Reports in Oncology
https://www.readbyqxmd.com/read/29279098/systematic-review-and-survival-meta-analysis-of-real-world-evidence-on-first-line-pazopanib-for-metastatic-renal-cell-carcinoma
#6
REVIEW
Miguel A Climent, José Muñoz-Langa, Laura Basterretxea-Badiola, Carmen Santander-Lobera
A systematic review was conducted to identify real world studies reporting outcomes after first-line pazopanib in patients with metastatic renal cell carcinoma. Studies had to be observational and report survival data in terms of progression-free survival and overall survival in order to conduct meta-analysis techniques. These real-world data were compared to those obtained in the phase II and III randomized controlled trials of pazopanib. Real world evidence showed that the clinical and safety outcomes were consistent with those observed in the clinical trials despite the inclusion of unselected patients with a wide spectrum of prognostic features and comorbidities...
January 2018: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/29277808/pazopanib-for-metastatic-renal-cell-carcinoma-a-registry-based-analysis-of-426-patients
#7
Alexandr Poprach, Ondrej Fiala, Renata Chloupkova, Bohuslav Melichar, Radek Lakomy, Katarina Petrakova, Milada Zemanova, Katerina Kopeckova, Ondrej Slaby, Hana Studentova, Jindrich Kopecký, Igor Kiss, Jindrich Finek, Ladislav Dusek, Tomas Buchler
BACKGROUND: Pazopanib is approved for the first-line treatment of patients with metastatic renal cell carcinoma (mRCC). The present study was a retrospective registry-based analysis of 426 patients with mRCC treated with pazopanib as first-line targeted therapy. PATIENTS AND METHODS: The data were obtained from the Renal Cell Carcinoma Information system registry. Patient baseline parameters, treatment course and outcomes, and toxicity were analysed. RESULTS: Median progression-free and overall survival were 12...
January 2018: Anticancer Research
https://www.readbyqxmd.com/read/29260644/recurrent-renal-cell-carcinoma-presenting-as-a-solitary-left-ventricular-mass
#8
Lindsay Wilde, Praveen Mehrotra, Jean Hoffman-Censits
A 73-year-old male with a remote history of renal cell carcinoma presented with an asymptomatic left ventricular mass. Biopsy of the mass revealed a late recurrence of his renal cell carcinoma. Given the size and location of the mass, resection was not possible. Treatment with pazopanib was initiated with good clinical response.
December 2017: Canadian Journal of Urology
https://www.readbyqxmd.com/read/29239846/molecular-subtypes-of-clear-cell-renal-cell-carcinoma-are-associated-with-outcome-during-pazopanib-therapy-in-the-metastatic-setting
#9
Annelies Verbiest, Gabrielle Couchy, Sylvie Job, Jessica Zucman-Rossi, Laure Caruana, Evelyne Lerut, Raymond Oyen, Aurélien de Reyniès, Brigitte Laguerre, Nathalie Rioux-Leclercq, Agnieszka Wozniak, Steven Joniau, Hendrik Van Poppel, Kathleen Van Den Eynde, Benoit Beuselinck
BACKGROUND: We previously described 4 molecular subtypes of metastatic clear cell renal cell carcinoma (mccRCC), named ccrcc1-4 (Beuselinck et al, 2015). These have both prognostic and predictive value for patients treated with first-line sunitinib, with distinctive objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). The ccrcc2 and ccrcc3 tumors have the best outcomes, followed by ccrcc1 and then ccrcc4. We hypothesized that these molecular subtypes would show similar outcomes with first-line pazopanib treatment...
November 7, 2017: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/29230117/outcomes-of-patients-with-late-relapse-metastatic-renal-cell-carcinoma-treated-with-targeted-therapies-a-single-institution-experience
#10
John Kucharczyk, Kamal Mandalapu, Suma Satti, Marc R Matrana
Background: Late relapse with presentation of metastatic disease >5 years after nephrectomy with curative intent is a known behavior of renal cell carcinoma (RCC), but data on outcomes, especially regarding targeted therapies, are limited. In this study, we analyze clinicopathologic features and response to targeted therapy in patients with late-relapse metastatic RCC (mRCC). Methods: We retrospectively reviewed clinical data on consecutive patients treated with targeted therapy for mRCC diagnosed >5 years after nephrectomy with curative intent...
2017: Ochsner Journal
https://www.readbyqxmd.com/read/29223605/updated-european-association-of-urology-guidelines-recommendations-for-the-treatment-of-first-line-metastatic-clear-cell-renal-cancer
#11
REVIEW
Thomas Powles, Laurence Albiges, Michael Staehler, Karim Bensalah, Saeed Dabestani, Rachel H Giles, Fabian Hofmann, Milan Hora, Markus A Kuczyk, Thomas B Lam, Lorenzo Marconi, Axel S Merseburger, Sergio Fernández-Pello, Rana Tahbaz, Alessandro Volpe, Börje Ljungberg, Axel Bex
The randomised phase III clinical trial Checkmate-214 showed a survival superiority for the combination of ipilimumab and nivolumab when compared with the previous standard of care in first-line metastatic/advanced clear cell renal cell carcinoma (RCC) (Escudier B, Tannir NM, McDermott DF, et al. CheckMate 214: efficacy and safety of nivolumab plus ipilimumab vs sunitinib for treatment-naïve advanced or metastatic renal cell carcinoma, including IMDC risk and PD-L1 expression subgroups. LBA5, ESMO 2017, 2017)...
December 6, 2017: European Urology
https://www.readbyqxmd.com/read/29200680/poor-risk-advanced-renal-cell-carcinoma-outcomes-from-a-registry-in-a-tertiary-cancer-center
#12
Anant Ramaswamy, Amit Joshi, Vanita Noronha, Vijay Patil, Arvind Sahu, Deepan R Manickam, Rushabh Kothari, Nilesh Sable, Archi Agrawal, Santosh Menon, Kumar Prabhash
Background: Poor-risk advanced Renal cell carcinoma (RCC) are an under-evaluated and difficult to treat subset of patients with poor prognosis. While Temsirolimus is the approved first line therapy for this category, Tyrosine kinase inhibitors (TKIs) are also commonly uses as initial treatment. We present an analysis of poor-risk advanced RCC treated in our institute. Materials and Methods: Patients diagnosed as poor-risk (as per Heng criteria) advanced RCC from June 2008 to December 2015 were analysed for baseline demographics, treatment received, toxicity (primarily Grade 3 and Grade 4), response rates (RR) and survival...
July 2017: Indian Journal of Medical and Paediatric Oncology
https://www.readbyqxmd.com/read/29198329/examining-the-bleeding-incidences-associated-with-targeted-therapies-used-in-metastatic-renal-cell-carcinoma
#13
REVIEW
MacKenzie Crist, Elizabeth Hansen, Lipika Chablani, Elizabeth Guancial
A systematic review was conducted to illustrate the bleeding risks associated with targeted therapies used in the treatment of metastatic renal cell carcinoma (mRCC). Eligible studies included phase II, III, or IV clinical trials using pazopanib, sunitinib, cabozantinib, lenvatinib, everolimus, temsirolimus, bevacizumab, axitinib, and/or sorafenib in the setting of mRCC. Types of bleeding event(s), bleeding event frequency, and incidence of thrombocytopenia were collected from the relevant articles. ClinicalTrials...
December 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/29195016/association-of-high-cost-sharing-and-targeted-therapy-initiation-among-elderly-medicare-patients-with-metastatic-renal-cell-carcinoma
#14
Pengxiang Li, Yu-Ning Wong, Jordan Jahnke, Amy R Pettit, Jalpa A Doshi
High out-of-pocket costs may limit access to oral therapies covered by patients' prescription drug benefits. We explored financial barriers to treatment initiation in patients newly diagnosed with metastatic renal cell carcinoma (mRCC) by comparing Medicare Part D patients with low out-of-pocket costs due to receipt of full low-income subsidies (LIS beneficiaries) to their counterparts who were responsible for more than 25% cost sharing during Medicare's initial coverage phase (non-LIS beneficiaries). We used 2011-2013 100% Medicare claims for non-LIS and LIS beneficiaries newly diagnosed with metastases in the liver, lung, or bone to examine targeted therapy treatment initiation rates and time to initiation for (1) oral medications (sorafenib, sunitinib, everolimus, pazopanib, or axitinib) covered under Medicare's prescription drug benefit (Part D); (2) injected or infused medications (temsirolimus or bevacizumab) covered by Medicare's medical benefit (Part B); and (3) any (Part D or Part B) targeted therapy...
December 1, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/29192741/taribo-trial-targeted-therapy-with-or-without-nephrectomy-in-metastatic-renal-cell-carcinoma-liquid-biopsy-for-biomarkers-discovery
#15
Elena Verzoni, Raffaele Ratta, Paolo Grassi, Roberto Salvioni, Silvia Stagni, Rosanna Montone, Giovanni Fucà, Vera Cappelletti, Carolina Reduzzi, Ugo De Giorgi, Giuseppe Procopio
PURPOSE: Two randomized trials in the cytokine era showed that cytoreductive nephrectomy (CN) had a role in metastatic renal cell carcinoma (mRCC), increasing life expectancy. The survival benefit of tyrosine kinase inhibitors (TKIs), including first-line sunitinib and pazopanib, in mRCC has been demonstrated, but the majority of patients enrolled in the pivotal phase III studies had undergone nephrectomy. Therefore it is unknown if similar survival benefit with targeted agents could be achieved without CN...
November 29, 2017: Tumori
https://www.readbyqxmd.com/read/29173270/clinical-outcomes-of-the-sequential-use-of-pazopanib-followed-by-everolimus-for-the-treatment-of-metastatic-renal-cell-carcinoma-a-multicenter-study-in-korea
#16
Jeong Ho Kim, Wan Lee, Tae Nam Kim, Jong Kil Nam, Tae Hyo Kim, Ki Soo Lee
INTRODUCTION: The aim of this study was to investigate the real-world clinical outcomes of first-line pazopanib and second-line everolimus in Korean patients with metastatic renal cell carcinoma (mRCC). METHODS: Data of patients who had mRCC with clear-cell component between 2001 and 2015 at multiple institutions were collected retrospectively. To be included in the analysis, patients had to meet the following criteria: age≥18 years; received first-line targeted therapy with pazopanib; and received second-line targeted therapy with everolimus...
December 1, 2017: Canadian Urological Association Journal, Journal de L'Association des Urologues du Canada
https://www.readbyqxmd.com/read/29172746/pazopanib-for-renal-cell-carcinoma-leads-to-elevated-mean-arterial-pressures-in-a-murine-model
#17
Amber Kempton, Cody Justice, Aaron Guo, Matthew Cefalu, Michael Makara, Paul Janssen, Thai H Ho, Sakima A Smith
BACKGROUND: In the setting of metastatic RCC (mRCC), pazopanib is approved as first line therapy. Unfortunately treatment may lead to cardiotoxicity such as hypertension, heart failure, and myocardial ischemia. OBJECTIVE: Define the in vivo role of pazopanib in the development of cardiotoxicity. METHODS: Wild type mice were dosed for 42 days via oral gavage, and separated into control and treatment (pazopanib) groups. Baseline ECG's, echocardiograms, and blood pressures were recorded...
November 27, 2017: Clinical and Experimental Hypertension: CHE
https://www.readbyqxmd.com/read/29172268/effect-of-targeted-therapy-with-pazopanib-on-expression-levels-of-transcription-growth-factors-and-components-of-akt-m-tor-signaling-pathway-in-patients-with-renal-cell-carcinoma
#18
Liudmila V Spirina, Evgeny A Usynin, Zahar A Yurmazov, Elena M Slonimskaya, Irina V Kondakova
Background: The effect of the targeted therapy on cancer molecular markers remains currently unknown. The aim of the study was to investigate the expression and content of transcription, growth factors and components of the AKT/m-TOR signaling pathway in kidney cancer patients before and after targeted therapy with pazopanib. Methods: A total of 157 patients with renal cell carcinoma were enrolled into the study. The level of mRNA expression was investigated by real-time PCR, and the contents of transcription and growth factors, as well as the levels of AKT/m- TOR signaling pathway components were determined by ELISA and Western blotting...
November 26, 2017: Asian Pacific Journal of Cancer Prevention: APJCP
https://www.readbyqxmd.com/read/29134564/seom-clinical-guideline-for-treatment-of-kidney-cancer-2017
#19
E Gallardo, M J Méndez-Vidal, J L Pérez-Gracia, J M Sepúlveda-Sánchez, M Campayo, I Chirivella-González, X García-Del-Muro, A González-Del-Alba, E Grande, C Suárez
The goal of this article is to provide recommendations about the management of kidney cancer. Based on pathologic and molecular features, several kidney cancer variants were described. Nephron-sparing techniques are the gold standard of localized disease. After a randomized trial, sunitinib could be considered in adjuvant treatment in high-risk patients. Patients with advanced disease constitute a heterogeneous population. Prognostic classification should be considered. Both sunitinib and pazopanib are the standard options for first-line systemic therapy in advanced renal cell carcinoma...
November 13, 2017: Clinical & Translational Oncology
https://www.readbyqxmd.com/read/29076108/clinical-and-economic-outcomes-in-elderly-advanced-renal-cell-carcinoma-patients-starting-pazopanib-or-sunitinib-treatment-a-retrospective-medicare-claims-analysis
#20
Nicholas J Vogelzang, Sumanta K Pal, Sameer R Ghate, Elyse Swallow, Nanxin Li, Miranda Peeples, Miriam L Zichlin, Mark K Meiselbach, Jose Ricardo Perez, Neeraj Agarwal
INTRODUCTION: Studies indicate similar survival and toxicity between pazopanib and sunitinib, but few have examined real-world outcomes among elderly patients with advanced renal cell carcinoma (RCC). The purpose of this retrospective claims analysis was to assess real-world overall survival (OS), healthcare resource utilization (HRU), and healthcare costs (both all-cause and associated with RCC diagnosis) among elderly advanced RCC patients starting pazopanib or sunitinib treatment. METHODS: Advanced RCC patients aged 65 years or older who started first-line treatment with pazopanib or sunitinib (index drug; the initiation date was the index date) were identified from the 100% Medicare database plus Part D linkage (January 1, 2006 to December 31, 2014)...
October 26, 2017: Advances in Therapy
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