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Pazopanib and renal cell carcinoma

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https://www.readbyqxmd.com/read/29786782/preclinical-impact-of-high-dose-intermittent-antiangiogenic-tyrosine-kinase-inhibitor-pazopanib-in-intrinsically-resistant-tumor-models
#1
Elaine Reguera-Nuñez, Shan Man, Ping Xu, Robert S Kerbel
Antiangiogenic tyrosine kinase inhibitors (TKIs) target vascular endothelial growth factor receptors and other receptor tyrosine kinases. As a result of toxicity, the clinical failures or the modest benefits associated with antiangiogenic TKI therapy may be related in some cases to suboptimal drug dosing and scheduling, thereby facilitating resistance. Most antiangiogenic TKIs, including pazopanib, are administered on a continuous daily basis. Here, instead, we evaluated the impact of increasing the dose and administering the drug intermittently...
May 21, 2018: Angiogenesis
https://www.readbyqxmd.com/read/29784193/adjuvant-vascular-endothelial-growth-factor-targeted-therapy-in-renal-cell-carcinoma-a-systematic-review-and-pooled-analysis
#2
REVIEW
Maxine Sun, Lorenzo Marconi, Tim Eisen, Bernard Escudier, Rachel H Giles, Naomi B Haas, Lauren C Harshman, David I Quinn, James Larkin, Sumanta K Pal, Thomas Powles, Christopher W Ryan, Cora N Sternberg, Robert Uzzo, Toni K Choueiri, Axel Bex
CONTEXT: Contradictory data exist with regard to adjuvant vascular endothelial growth factor receptor (VEGFR)-targeted therapy in surgically managed patients for localized renal cell carcinoma (RCC). OBJECTIVE: To systematically evaluate the current evidence regarding the therapeutic benefit (disease-free survival [DFS] and overall survival [OS]) and grade 3-4 adverse events (AEs) for adjuvant VEGFR-targeted therapy for resected localized RCC. EVIDENCE ACQUISITION: A critical review of PubMed/Medline, Embase, and the Cochrane Library in January 2018 according to the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) statement was performed...
May 18, 2018: European Urology
https://www.readbyqxmd.com/read/29783587/re-randomized-phase-iii-trial-of-adjuvant-pazopanib-versus-placebo-after-nephrectomy-in-patients-with-localized-or-locally-advanced-renal-cell-carcinoma
#3
https://www.readbyqxmd.com/read/29774795/prospective-evaluation-of-hypogonadism-in-male-metastatic-renal-cell-carcinoma-patients-treated-with-targeted-therapies
#4
Julie Bastin, Emilie Werbrouck, Annelies Verbiest, Kevin Punie, Oliver Bechter, Sherida Feng Woei-A-Jin, Pascal Wolter, Hans Wildiers, Evelyne Lerut, Herlinde Dumez, Brigitte Decallonne, Paul Clement, Dirk Vanderschueren, Maarten Albersen, Raymond Oyen, Patrick Schöffski, Benoit Beuselinck
Objectives To study the prevalence of hypogonadism in male patients with metastatic renal cell carcinoma (mRCC) starting with targeted therapies and the impact of the vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs) sunitinib and pazopanib on the luteinizing hormone (LH)/testosterone (TT)-axis. Methods Male mRCC patients starting with targeted therapies were prospectively included in this study. TT- and LH-levels were sampled at start as well as during systemic therapy. Endpoints of the study were gonadal status (TT- and LH-levels) at start of targeted therapy and TT- and LH-evolution during targeted therapy...
May 18, 2018: Acta Clinica Belgica
https://www.readbyqxmd.com/read/29708353/-treatment-of-metastatic-renal-cell-carcinoma
#5
Igor Richter, Josef Dvořák
INTRODUCTION: Renal cell cancer accounts for approximately 2-3% of all cases of malignancy. The incidence of kidney cancer in the Czech Republic is the highest in the world. Approximately 70% of renal cell carcinomas are clear-cell renal cancer. Various treatment options for metastatic renal cell cancer (mRCC) have been developed. Treatment regimens comprise antiangiogenic drugs in combination with vascular endothelial growth factor receptor inhibitors, mTOR inhibitors, and immunotherapy...
2018: Klinická Onkologie: Casopis Ceské a Slovenské Onkologické Spolecnosti
https://www.readbyqxmd.com/read/29706106/the-impact-of-pazopanib-on-the-cardiovascular-system
#6
Cody N Justice, Mohamed H Derbala, Tesla M Baich, Amber N Kempton, Aaron S Guo, Thai H Ho, Sakima A Smith
Pazopanib is an approved treatment for renal cell carcinoma and a second-line treatment for nonadipocytic soft-tissue sarcoma. However, its clinical efficacy is limited by its cardiovascular side effects. Pazopanib and other vascular endothelial growth factor receptor tyrosine kinase inhibitors have been associated with the development of hypertension, QT interval prolongation, and other cardiovascular events; however, these mechanisms are largely unknown. Gaining a deeper understanding of these mechanisms is essential for the development of appropriate surveillance strategies and possible diagnostic biomarkers to allow us to monitor patients and modulate therapy prior to significant cardiac insult...
January 1, 2018: Journal of Cardiovascular Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29700053/tk-inhibitor-pazopanib-primes-dcs-by-downregulation-of-the-%C3%AE-catenin-pathway
#7
Ilaria Grazia Zizzari, Chiara Napoletano, Andrea Botticelli, Salvatore Caponnetto, Fabio Calabrò, Alain Gelibter, Aurelia Rughetti, Ilary Ruscito, Hassan Rahimi, Ernesto Rossi, Giovanni Schinzari, Paolo Marchetti, Marianna Nuti
Tyrosine kinase inhibitors (TKIs) target angiogenesis by affecting, for example, the VEGF receptors in tumors and have improved outcomes for patients with metastatic renal cell carcinoma (mRCC). Immune checkpoint inhibitors (ICIs) have also been proposed for treatment of mRCC with encouraging results. A better understanding of the activity of immune cells in mRCC, the immuneomodulatory effects of TKIs, and the characteristics defining patients most likely to benefit from various therapies will help optimize immunotherapeutic approaches...
April 26, 2018: Cancer Immunology Research
https://www.readbyqxmd.com/read/29692506/efficacy-and-safety-of-third-and-fourth-line-targeted-therapy-in-japanese-patients-with-metastatic-renal-cell-carcinoma-a-retrospective-analysis
#8
Negishi Takahito, Nagase Kei, Iwai Hidenori, Furubayashi Nobuki, Taguchi Kenichi, Nakamura Motonobu
Introduction: There is limited data on the efficacy of sequential targeted therapy for metastatic renal cell carcinoma (mRCC) beyond the second line, especially for Asian patients. We evaluated the efficacy and side effects of targeted therapy beyond the second line. Materials and Methods: We retrospectively reviewed 69 patients who were administered targeted therapy for mRCC at our institution between 2008 and 2016. Sunitinib, pazopanib, sorafenib, axitinib, everolimus, and temsirolimus were available in Japan in 2016, and treatment had been conducted with those six agents...
April 2018: Indian Journal of Urology: IJU: Journal of the Urological Society of India
https://www.readbyqxmd.com/read/29684209/drug-review-pazopanib
#9
Shingo Miyamoto, Shigenori Kakutani, Yujiro Sato, Akira Hanashi, Yoshitaka Kinoshita, Akira Ishikawa
Pazopanib (Votrient®) is an oral small-molecule multi-kinase inhibitor that primarily inhibits vascular endothelial growth factor receptor-1, -2 and -3, platelet endothelial growth factor receptor-α, and -β, and the stem-cell factor receptor c-kit. In preliminary experiments using angiogenesis models with mice and rabbits, pazopanib inhibited angiogenesis caused by combined vascular endothelial growth factor and basic fibroblast growth factor. Although pazopanib was developed as a therapeutic agent against various tumors, it is currently approved in many countries for advanced soft-tissue sarcoma and renal cell carcinoma...
April 19, 2018: Japanese Journal of Clinical Oncology
https://www.readbyqxmd.com/read/29669553/significant-response-to-nivolumab-for-metastatic-chromophobe-renal-cell-carcinoma-with-sarcomatoid-differentiation-a-case-report
#10
Go Noguchi, Sohgo Tsutsumi, Masato Yasui, Shinji Ohtake, Susumu Umemoto, Noboru Nakaigawa, Masahiro Yao, Takeshi Kishida
BACKGROUND: The treatment of advanced or metastatic renal cell carcinoma (RCC) has drastically changed since the approval of immune checkpoint therapy. Nivolumab is a treatment option for patients with metastatic RCC, previously treated with targeted antiangiogenic therapy. The efficacy of nivolumab for patients with RCC was established by the Checkmate 025 clinical trial. Chromophobe RCC (CRCC) represents around 5% of RCC cases, but non-clear cell RCC (non-ccRCC) subtypes were excluded from the Checkmate 025 clinical trial...
April 18, 2018: BMC Urology
https://www.readbyqxmd.com/read/29629905/presurgical-pazopanib-for-renal-cell-carcinoma-with-inferior-vena-caval-thrombus-a-single-institution-study
#11
Tomoaki Terakawa, Ahmed A Hussein, Yukari Bando, Khurshid A Guru, Junya Furukawa, Katsumi Shigemura, Kenichi Harada, Nobuyuki Hinata, Yuzou Nakano, Masato Fujisawa
The aim of this study was to investigate the clinical benefit of presurgical therapy with pazopanib in renal cell carcinoma (RCC) patients with a tumor thrombus extending to a high level in the vena cava. A retrospective review was performed for seven consecutive patients with RCC and tumor thrombus involving the vena cava above the hepatic vein (level 3-4, Mayo Clinic classification) treated with pazopanib without initial cytoreductive nephrectomy at our institution. The effect of pazopanib was assessed in terms of the primary site response, thrombus diameter, and height (before and after treatment) on computed tomography or MRI...
April 6, 2018: Anti-cancer Drugs
https://www.readbyqxmd.com/read/29589470/the-merit-of-tyrosine-kinase-inhibitors-in-the-adjuvant-setting-of-high-risk-renal-cell-carcinoma-a-meta-analysis
#12
Hampig Raphael Kourie, Ziad Bakouny, Roland Eid, Fady Gh Haddad, Joseph Kattan
AIM: As no meta-analyses have evaluated tyrosine kinase inhibitors in the adjuvant setting of high-risk renal cell carcinoma (RCC), the aim was to evaluate the benefit of sunitinib and pazopanib in the adjuvant setting. METHODS: This meta-analysis included all Phase III randomized controlled trials evaluating adjuvant sunitinib and pazopanib in high-risk RCC. Primary outcome was the comparison of disease-free survival (DFS) between tyrosine kinase inhibitors and placebo...
March 28, 2018: Future Oncology
https://www.readbyqxmd.com/read/29571135/simultaneous-monitoring-of-pazopanib-and-its-metabolites-by-uplc-ms-ms
#13
Marie-Noëlle Paludetto, Florent Puisset, Félicien Le Louedec, Ben Allal, Thierry Lafont, Etienne Chatelut, Cécile Arellano
Pazopanib is a multi-targeted tyrosine kinase inhibitor (TKI) approved as first-line treatment for patients with advanced renal cell carcinoma (RCC) and as second-line treatment for patients with advanced soft tissue sarcoma (STS) previously treated with chemotherapy. The most common adverse events, observed during the RCC and STS trials, were gastrointestinal disorders, hypertension, fatigue, elevated ALAT and ASAT, but the molecular mechanisms explaining pazopanib toxicity remain unclear. Therapeutic activity is considered to be mainly dependent on pazopanib exposure as the primary metabolites are inactive or display low plasma concentrations, but metabolites may be involved in toxicity as relationships between metabolite profiles and toxicity have not been evaluated...
March 9, 2018: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/29556268/molecular-targeted-therapies-of-renal-cell-carcinoma-considering-life-stage-of-the-patient-two-case-reports
#14
Hisashi Takeuchi, Naoto Tokuyama, Isao Kuroda, Teiichiro Aoyagi
Molecular targeted therapies have markedly improved the prognosis of metastatic renal cell carcinoma (RCC) and patients are able to receive specific treatments depending on their condition. The cases of two patients who presented with large RCC with very different statuses were examined in the current study. One of the patients was elderly with numerous comorbidities, and the other was young and had Case 1 was an elderly female with various comorbidities including a history of cerebral infarction and impaired eyesight...
April 2018: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29554654/radiotherapy-and-vascular-endothelial-growth-factor-receptor-tyrosine-kinase-inhibitors-in-renal-cancer
#15
Michele Fiore, Rolando Maria D Apos Angelillo, Carlo Greco, Iacopo Fioroni, Edy Ippolito, Daniele Santini, Sara Ramella
Treatment of metastatic renal cell carcinoma (mRCC) has seen substantial progress over the last decade. A number of targeted therapies have been shown to improve clinical outcome. Vascular endothelial growth factor receptor (VEGFR)-tyrosine kinase inhibitors (TKIs) are an effective option in treating mRCC. RCC is traditionally perceived to be a radioresistant malignancy with a limited role of radiotherapy (RT) in the management of localized disease. While RCC appears to be radioresistant using conventionally fractionated RT, preclinical data suggest increased radiosensitivity when an ablative, hypofractionated schedule is used...
March 19, 2018: Chemotherapy
https://www.readbyqxmd.com/read/29487220/effect-of-concomitant-ph-elevating-medications-with-pazopanib-on-progression-free-survival-and-overall-survival-in-patients-with-metastatic-renal-cell-carcinoma
#16
Renee K McAlister, Jonathan Aston, Megan Pollack, Liping Du, Tatsuki Koyama, David D Chism
BACKGROUND: Pazopanib is an oral tyrosine-kinase inhibitor that is approved by the U.S. Food and Drug Administration for treatment of metastatic renal cell carcinoma (mRCC). Pharmacokinetic data have shown that concomitant administration of pazopanib and esomeprazole, a proton pump inhibitor (PPI), leads to decreased area under the curve and thus decreased exposure of pazopanib by 40%. Despite the pharmacokinetic data published to date, the clinical significance and impact on patient outcomes resulting from decreased pazopanib exposure remains unknown...
February 27, 2018: Oncologist
https://www.readbyqxmd.com/read/29464464/pazopanib-related-tumor-lysis-syndrome-in-metastatic-clear-cell-renal-cell-carcinoma-a-case-report
#17
Michael W van Kalleveen, Maudy Walraven, Mathijs P Hendriks
Introduction Tumor lysis syndrome (TLS) is a life-threatening emergency caused by rapid cell death as a result of anti-tumor therapy. In the era of targeted therapy it has increasingly been observed in solid malignancies such as hepatocellular carcinoma (HCC) and renal cell carcinoma (RCC). Case We describe the case of a 58-year old man with the medical history of a memorial sloan kettering cancer centre (MSKCC) poor prognosis metastasized clear cell renal cell carcinoma (mRCC) who developed TLS within six days after initiating therapy with the tyrosine kinase inhibitor (TKI) pazopanib...
February 20, 2018: Investigational New Drugs
https://www.readbyqxmd.com/read/29463434/molecular-subtypes-of-clear-cell-renal-cell-carcinoma-are-prognostic-for-outcome-after-complete-metastasectomy
#18
Annelies Verbiest, Gabrielle Couchy, Sylvie Job, Laure Caruana, Evelyne Lerut, Raymond Oyen, Aurélien de Reyniès, Lorenzo Tosco, Steven Joniau, Hendrik Van Poppel, Dirk Van Raemdonck, Kathleen Van Den Eynde, Agnieszka Wozniak, Jessica Zucman-Rossi, Benoit Beuselinck
BACKGROUND: Metastasectomy is routinely performed in selected patients with metastatic clear-cell renal cell carcinoma (ccRCC) as an alternative to systemic therapy. In the absence of randomized trials, the benefit and best way of patient selection remain unclear. Earlier, we described four molecular ccRCC-subtypes (ccrcc1-4) that have a prognostic and predictive value upon first-line sunitinib or pazopanib. OBJECTIVE: Assess the prognostic value of ccrcc1-4 subtypes after complete metastasectomy...
February 17, 2018: European Urology
https://www.readbyqxmd.com/read/29454306/record-4-multicenter-phase-2-trial-of-second-line-everolimus-in-patients-with-metastatic-renal-cell-carcinoma-asian-versus-non-asian-population-subanalysis
#19
Lin Yang, Anna Alyasova, Dingwei Ye, Antonia Ridolfi, Luca Dezzani, Robert J Motzer
BACKGROUND: RECORD-4 assessed everolimus in patients with metastatic renal cell carcinoma (mRCC) who progressed after 1 prior anti-vascular endothelial growth factor (VEGF) or cytokine and reinforced the clinical benefit of second-line everolimus. Because of the high percentage of patients from China enrolled in RECORD-4 (41%) and some reported differences in responses to certain targeted agents between Chinese and Western patients, this subanalysis evaluated outcomes in Asian versus non-Asian patients...
February 17, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29449091/adjuvant-therapies-in-nonmetastatic-renal-cell-carcinoma-a-review-of-the-literature
#20
REVIEW
Marco Bandini, Ariane Smith, Michele Marchioni, Raisa S Pompe, Tristan F Martel, Luca Cindolo, Francesco Montorsi, Shahrokh F Shariat, Alberto Briganti, Anil Kapoor, Umberto Capitanio, Pierre I Karakiewicz
To conduct a review of literature on adjuvant therapy in nonmetastatic renal-cell carcinoma (nmRCC) treated with nephrectomy and to describe the efficacy of adjuvant agents on cancer control outcomes. A review of the literature was performed in January 2018 to identify all studies evaluating adjuvant therapy in patients with nmRCC treated with nephrectomy using PubMed, Embase, Medline, and Cochrane Library databases. The following keywords were used: adjuvant therapy, renal-cell carcinoma, nonmetastatic, targeted molecular therapy, kidney cancer...
February 2, 2018: Clinical Genitourinary Cancer
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