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https://www.readbyqxmd.com/read/28330784/vascular-endothelial-growth-factor-vegf-and-vegf-receptor-inhibitors-in-the-treatment-of-renal-cell-carcinomas
#1
REVIEW
Robert Roskoski
One Von Hippel-Lindau (VHL) tumor suppressor gene is lost in most renal cell carcinomas while the nondeleted allele exhibits hypermethylation-induced inactivation or inactivating somatic mutations. As a result of these genetic modifications, there is an increased production of VEGF-A and pro-angiogenic growth factors in this disorder. The important role of angiogenesis in the pathogenesis of renal cell carcinomas and other tumors has focused the attention of investigators on the biology of VEGFs and VEGFR1-3 and to the development of inhibitors of the intricate and multifaceted angiogenic pathways...
March 18, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28276433/renal-cell-carcinoma
#2
REVIEW
James J Hsieh, Mark P Purdue, Sabina Signoretti, Charles Swanton, Laurence Albiges, Manuela Schmidinger, Daniel Y Heng, James Larkin, Vincenzo Ficarra
Renal cell carcinoma (RCC) denotes cancer originated from the renal epithelium and accounts for >90% of cancers in the kidney. The disease encompasses >10 histological and molecular subtypes, of which clear cell RCC (ccRCC) is most common and accounts for most cancer-related deaths. Although somatic VHL mutations have been described for some time, more-recent cancer genomic studies have identified mutations in epigenetic regulatory genes and demonstrated marked intra-tumour heterogeneity, which could have prognostic, predictive and therapeutic relevance...
March 9, 2017: Nature Reviews. Disease Primers
https://www.readbyqxmd.com/read/28264536/-a-case-of-papillary-renal-cell-carcinoma-40-years-after-radiation-therapy
#3
Kenta Onishi, Satoshi Anai, Yusuke Iemura, Yasushi Nakai, Makito Miyake, Yoshitomo Chihara, Nobumichi Tanaka, Kiyohide Fujimoto
Here, we report a case of papillary renal cell carcinoma in a 47-year-old woman. In 1970 (at 5 years old), she was diagnosed with Wilms tumor in her right kidney, and underwent surgery. However, nephrectomy was not possible. Consequently, she received radiation therapy (61. 5 Gy) at the former hospital. Thereafter, the patient regularly visited her physician and had no further problems. In 1998 (at 33 years old), blood was detected in her urine, and renal cell carcinoma was suspected. A computed tomography (CT)-guided biopsy was performed, but tissue collection was difficult due to calcification of the renal parenchyma after radiation treatment...
February 2017: Hinyokika Kiyo. Acta Urologica Japonica
https://www.readbyqxmd.com/read/28262413/checkmate-025-randomized-phase-3-study-outcomes-by-key-baseline-factors-and-prior-therapy-for-nivolumab-versus-everolimus-in-advanced-renal-cell-carcinoma
#4
Bernard Escudier, Padmanee Sharma, David F McDermott, Saby George, Hans J Hammers, Sandhya Srinivas, Scott S Tykodi, Jeffrey A Sosman, Giuseppe Procopio, Elizabeth R Plimack, Daniel Castellano, Howard Gurney, Frede Donskov, Katriina Peltola, John Wagstaff, Thomas C Gauler, Takeshi Ueda, Huanyu Zhao, Ian M Waxman, Robert J Motzer
BACKGROUND: The randomized, phase 3 CheckMate 025 study of nivolumab (n=410) versus everolimus (n=411) in previously treated adults (75% male; 88% white) with advanced renal cell carcinoma (aRCC) demonstrated significantly improved overall survival (OS) and objective response rate (ORR). OBJECTIVE: To investigate which baseline factors were associated with OS and ORR benefit with nivolumab versus everolimus. DESIGN, SETTING, AND PARTICIPANTS: Subgroup OS analyses were performed using Kaplan-Meier methodology...
March 2, 2017: European Urology
https://www.readbyqxmd.com/read/28253548/patterns-of-care-among-patients-receiving-sequential-targeted-therapies-for-advanced-renal-cell-carcinoma-a-retrospective-chart-review-in-the-usa
#5
Sumanta K Pal, James E Signorovitch, Nanxin Li, Miriam L Zichlin, Zhimei Liu, Sameer R Ghate, Jose Ricardo Perez, Nicholas J Vogelzang
OBJECTIVES: To assess real-world treatment patterns of targeted therapies after failure of first-line tyrosine kinase inhibitors in patients with advanced renal cell carcinoma. METHODS: A large, retrospective review of medical charts of patients with advanced renal cell carcinoma in the USA was carried out. Descriptive statistics were used to summarize physicians' and patients' characteristics, treatment sequences, and reasons for treatment choices. P-values were calculated using χ(2) -tests for categorical variables and Wilcoxon rank-sum tests for continuous variables...
March 2, 2017: International Journal of Urology: Official Journal of the Japanese Urological Association
https://www.readbyqxmd.com/read/28249615/secondary-hemophagocytic-lymphohistiocytosis-in-the-setting-of-metastatic-renal-cell-carcinoma-a-case-report
#6
Monica El-Masry, Lauren Eisenbud, Minh-Ha Tran
BACKGROUND: Hemophagocytic lymphohistiocytosis is a disease process characterized by unregulated hyperactivation of the immune system associated with multiorgan involvement and high mortality rates. Early recognition is crucial and a recently validated diagnostic schema, the H-Score, may facilitate diagnosis particularly in secondary hemophagocytic lymphohistiocytosis cases. We present a patient with secondary hemophagocytic lymphohistiocytosis in association with metastatic renal cell carcinoma in whom high-dose steroid therapy induced a remarkable response...
March 2, 2017: Journal of Medical Case Reports
https://www.readbyqxmd.com/read/28221861/inhibiting-histone-deacetylase-as-a-means-to-reverse-resistance-to-angiogenesis-inhibitors-phase-i-study-of-abexinostat-plus-pazopanib-in-advanced-solid-tumor-malignancies
#7
Rahul Aggarwal, Scott Thomas, Nela Pawlowska, Imke Bartelink, Jennifer Grabowsky, Thierry Jahan, Amy Cripps, Armand Harb, Jim Leng, Anne Reinert, Ilaria Mastroserio, Thach-Giao Truong, Charles J Ryan, Pamela N Munster
Purpose This phase I trial evaluated epigenetic modulation of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor by using a histone deacetylase abexinostat in combination with pazopanib to enhance response and reverse resistance. Patients and Methods Pazopanib was administered once a day on days 1 to 28 and abexinostat was administered orally twice a day on days 1 to 5, 8 to 12, and 15 to 19 (schedule A) or on days 1 to 4, 8 to 11, and 15 to 18 (schedule B). Dose escalation (3 + 3 design) in all solid tumors was followed by dose expansion in renal cell carcinoma (RCC)...
February 21, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28208511/re-first-line-sunitinib-versus-pazopanib-in-metastatic-renal-cell-carcinoma-results-from-the-international-metastatic-renal-cell-carcinoma-database-consortium
#8
https://www.readbyqxmd.com/read/28197036/induction-of-trismus-by-sunitinib-and-pazopanib-in-metastatic-renal-cell-carcinoma
#9
Ridhima Iyer, Bruce Montgomery, Hardev S Pandha
Tyrosine kinase inhibitors sunitinib and pazopanib are used as first-line agents in the treatment of metastatic renal cell carcinoma. Treatment-related toxicities have been described with both these drugs. This report describes a patient with metastatic renal carcinoma who developed trismus while being treated with these agents and is, to the best of our knowledge, the first such case to be reported.
January 2017: Indian Journal of Urology: IJU: Journal of the Urological Society of India
https://www.readbyqxmd.com/read/28185218/clinical-pharmacokinetics-and-pharmacodynamics-of-pazopanib-towards-optimized-dosing
#10
REVIEW
Remy B Verheijen, Jos H Beijnen, Jan H M Schellens, Alwin D R Huitema, Neeltje Steeghs
Pazopanib is an inhibitor of the vascular endothelial growth factor receptor, platelet-derived growth factor receptor, fibroblast growth factor receptor and stem cell receptor c-Kit, and has been approved for the treatment of renal cell carcinoma and soft tissue sarcoma. The pharmacokinetics of pazopanib are complex and are characterized by pH-dependent solubility, large interpatient variability and low, non-linear and time-dependent bioavailability. Exposure to pazopanib is increased by both food and coadministration of ketoconazole, but drastically reduced by proton pump inhibitors...
February 10, 2017: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/28152737/financial-risk-sharing-agreements-using-options-to-make-marginal-benefits-cost-effective
#11
(no author information available yet)
41 Background: New cancer treatments have become increasingly costly. Although new drugs may be sufficiently cost-efficiency for a primary indication (i1) to receive funding, subsequent indications (ia) may not prove cost-effective. A financial risk-sharing agreement to increase access is proposed. A potential 2012 real-world implementation in Canada for pazopanib use in metastatic renal cell carcinoma (mRCC) as i1, and soft-tissue sarcoma (STS) as ia is presented. METHODS: The market value of an indication can be approximated by its net-present-value (NPV) of expected cash flows...
March 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28152689/comparative-effectiveness-research-in-renal-cell-carcinoma-lenvatinib-with-everolimus-as-a-potential-new-treatment-option
#12
Corey Pelletier, Unnati Majethia, Anna Forsythe
27 Background: Renal cell carcinoma (RCC) is the most common type of kidney cancer and represents about 90% of all kidney cancers. As comprehensive comparison of the efficacy associated with mRCC treatments is not available, the goal of this research was to provide a comparative effectiveness analysis including overall survival (OS) and progression free survival (PFS) for first and second line treatments. METHODS: Systematic literature review yielded the following randomized active-controlled studies: lenvatinib + everolimus (LEN+EVE) versus everolimus (EVE), axinitib (AXI) versus sorafenib (SOR), cabozantinib (CAB) versus EVE, nivolumab (NIV) versus EVE, and pazopanib (PAZ) versus sunitinib (SUN)...
March 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28144093/managing-metastatic-renal-cell-carcinoma-challenges-pitfalls-and-outcomes-in-the-real-world
#13
Karnam Ashok Kumar, Gundeti Sadashivudu, K V Krishnamani, Vijay Gandhi Linga, Lakshmi Srinivas Maddali, Raghunadha Rao Digumarti
INTRODUCTION: Renal cell carcinoma (RCC) is the most common cancer of the kidney accounting for 85% of renal tumors. Metastatic RCC (mRCC) had a poor prognosis and with the introduction of tyrosine-kinase inhibitors, such as sunitinib, pazopanib the outcomes improved. There is only one study reported from India on the use of sunitinib in mRCC. We present our analysis of mRCC and use of sunitinib at our institute over 5 years. MATERIALS AND METHODS: All patients with mRCC receiving sunitinib were analyzed with respect to patient characteristics, response, toxicity, and outcomes...
October 2016: Indian Journal of Medical and Paediatric Oncology
https://www.readbyqxmd.com/read/28143997/targeted-therapy-for-metastatic-renal-cell-carcinoma
#14
REVIEW
Andika Afriansyah, Agus Rizal Ah Hamid, Chaidir A Mochtar, Rainy Umbas
In the past 10 years, recent development of targeted therapy in metastatic renal cell carcinoma (mRCC) has provided a new hope and significantly enhanced the prognosis of the disease. Three class of targeted therapy were developed, including multi-targeted tyrosine kinase inhibitors (TKI), the mammalian target of rapamycin (mTOR) complex-1 kinase inhibitors, and the humanized antivascular endothelial growth factor (VEGF) monoclonal antibody. Hence, the objective of this article was to critically examine the current evidence of targeted therapy treatment for patients with mRCC...
October 2016: Acta Medica Indonesiana
https://www.readbyqxmd.com/read/28139444/real-world-survival-outcomes-and-prognostic-factors-among-patients-receiving-first-targeted-therapy-for-advanced-renal-cell-carcinoma-a-seer-medicare-database-analysis
#15
Sumanta K Pal, Sameer R Ghate, Nanxin Li, Elyse Swallow, Miranda Peeples, Miriam L Zichlin, Jose Ricardo Perez, Neeraj Agarwal, Nicholas J Vogelzang
BACKGROUND: The real-world survival outcomes and prognostic factors among patients receiving first-line targeted therapy for advanced renal cell carcinoma (aRCC) are not well known. PATIENTS AND METHODS: Adult patients diagnosed with RCC and treated with first-line targeted therapy were identified from the Surveillance, Epidemiology, and End Results-Medicare database (January 1, 1993 to December 31, 2012). The patients were grouped into early (2006-2009) or late (2010-2012) targeted therapy era cohorts by the year of the first-line targeted therapy initiation...
January 5, 2017: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/28108284/first-line-pazopanib-in-non-clear-cell-renal-carcinoma-the-italian-retrospective-multicenter-panorama-study
#16
Sebastiano Buti, Melissa Bersanelli, Francesca Maines, Gaetano Facchini, Francesco Gelsomino, Fable Zustovich, Matteo Santoni, Elena Verri, Ugo De Giorgi, Cristina Masini, Franco Morelli, Maria Giuseppa Vitale, Teodoro Sava, Giuseppe Prati, Carmelinda Librici, Anna Paola Fraccon, Giuseppe Fornarini, Marco Maruzzo, Francesco Leonardi, Orazio Caffo
INTRODUCTION: Pazopanib is a standard first-line treatment for metastatic clear-cell renal cell carcinoma (ccRCC). Very few data on its activity in non-clear-cell renal cell carcinoma (nccRCC) are currently available. The aim of this study was to retrospectively analyze efficacy and toxicity of pazopanib in nccRCC patients. PATIENTS AND METHODS: Records from advanced nccRCC patients (consecutive sample) treated with first-line pazopanib between 2010 and 2015 at 17 Italian centers were reviewed...
December 29, 2016: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/28096934/first-line-treatment-options-in-metastatic-renal-cell-cancer
#17
REVIEW
Anil Kapoor
The introduction of targeted therapy a decade ago revolutionized the treatment of metastatic renal cell carcinoma (mRCC). The current standard of care focuses on the inhibition of angiogenesis through the targeting of the vascular endothelial growth factor receptor (VEGFR) and the mammalian target of rapamycin (mTOR). Currently recommended first-line treatments in Canada include sunitinib, pazopanib, and temsirolimus. With the heterogeneity of mRCC disease, the choice of treatment is driven largely by prognostic factors...
November 2016: Canadian Urological Association Journal, Journal de L'Association des Urologues du Canada
https://www.readbyqxmd.com/read/28089721/angiotensin-inhibitors-as-treatment-of-sunitinib-pazopanib-induced-hypertension-in%C3%A2-metastatic-renal-cell-carcinoma
#18
Patrick Penttilä, Juhana Rautiola, Tuija Poussa, Katriina Peltola, Petri Bono
BACKGROUND: Research suggests that baseline use of angiotensin system inhibitors (ASIs) improves outcome in patients with metastatic renal cell carcinoma (mRCC), but it remains unknown whether the type of antihypertensive medication used to initiate management at onset of treatment-induced hypertension (HTN) is associated with outcome. We evaluated the association of ASIs and outcome among patients with mRCC treated with first-line tyrosine kinase inhibitors (TKIs). PATIENTS AND METHODS: We identified 303 consecutive patients with mRCC who were treated with sunitinib or pazopanib in a single university hospital cancer center...
December 22, 2016: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/28077238/patterns-of-care-and-clinical-outcomes-in-patients-with-metastatic-renal-cell-carcinoma-results-from-a-tertiary-cancer-center-in-india
#19
Anant Ramaswamy, Amit Joshi, Vanita Noronha, Vijay M Patil, Rushabh Kothari, Arvind Sahu, Ram Abhinav Kannan, Nilesh Sable, Palak Popat, Santosh Menon, Kumar Prabhash
INTRODUCTION: The current treatment of metastatic renal cell carcinoma (mRCC) revolves around targeted agents, which have resulted in a median overall survival of 22 to 26 months in registration trials. However, the outcomes in a non-trial, real-world Indian population have not yet been evaluated. MATERIALS AND METHODS: The present study was a part of a prospective Clinical Trials Registry-India-registered study, the Kidney Cancer Registry, a prospectively maintained kidney cancer registry...
October 19, 2016: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/27986807/effects-of-4-multitargeted-receptor-tyrosine-kinase-inhibitors-on-regional-hemodynamics-in-conscious-freely-moving-rats
#20
Joanne J Carter, Laurice V Fretwell, Jeanette Woolard
VEGF inhibitors, including receptor tyrosine kinase inhibitors, are used as adjunct therapies in a number of cancer treatments. An emerging issue with these drugs is that most cause hypertension. To gain insight into the physiological mechanisms involved, we evaluated their regional hemodynamic effects in conscious rats. Male Sprague Dawley rats (350-450 g) were chronically implanted with pulsed Doppler flow probes (renal and mesenteric arteries, and the descending abdominal aorta) and catheters (jugular vein, peritoneal cavity, and distal abdominal aorta)...
March 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
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