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Adjuvant sunitinib

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https://www.readbyqxmd.com/read/30412222/adjuvant-sunitinib-in-patients-with-high-risk-renal-cell-carcinoma-safety-therapy-management-and-patient-reported-outcomes-in-the-s-trac-trial
#1
M Staehler, R J Motzer, D J George, H S Pandha, F Donskov, B Escudier, A J Pantuck, A Patel, L DeAnnuntis, H Bhattacharyya, K Ramaswamy, G Zanotti, X Lin, M Lechuga, L Serfass, J Paty, A Ravaud
Background: Adjuvant sunitinib has significantly improved disease-free survival versus placebo in patients with renal cell carcinoma at high risk of recurrence post-nephrectomy (hazard ratio 0.76; 95% confidence interval, 0.59-0.98; two-sided P = 0.03). We report safety, therapy management, and patient-reported outcomes for patients receiving sunitinib and placebo in the S-TRAC trial. Patients and methods: Patients were stratified by the University of California, Los Angeles Integrated Staging System and Eastern Cooperative Oncology Group performance status score, and randomized (1 : 1) to receive sunitinib (50 mg/day) or placebo...
October 1, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/30401688/phase-iii-trial-of-adjuvant-sunitinib-in-patients-with-high-risk-renal-cell-carcinoma-exploratory-pharmacogenomic-analysis
#2
Daniel J George, Jean-Francois Martini, Michael Staehler, Robert J Motzer, Ahmed Magheli, Frede Donskov, Bernard Escudier, Sherry Li, Michelle Casey, Olga Valota, Brigitte Laguerre, Allan J Pantuck, Hardev Pandha, Anup Patel, Maria J Lechuga, Alain Ravaud
PURPOSE: In the S-TRAC trial, adjuvant sunitinib prolonged disease-free survival (DFS) versus placebo in patients with loco-regional renal cell carcinoma at high risk of recurrence after nephrectomy. An exploratory analysis evaluated associations between single nucleotide polymorphisms (SNPs) in several angiogenesis- or hypoxia-related genes and clinical outcomes in S-TRAC. EXPERIMENTAL DESIGN: Blood samples were genotyped for 10 SNPs and one insertion/deletion mutation using TaqMan assays...
November 6, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/30372398/perioperative-therapy-in-renal-cell-carcinoma-what-do-we-know-what-have-we-learned-what-s-next
#3
Naomi B Haas, Robert G Uzzo
Recent adjuvant vascular endothelial growth factor tyrosine kinase inhibitor trials in resected high-risk renal cell carcinoma that compared sunitinib, sorafenib, pazopanib, and axitinib with placebo controls have demonstrated mixed impact on disease-free survival, no improvement in overall survival, and, thus, controversy. Here, we discuss the results and conduct of these trials to provide new insight into the goals and strategies of treating resected renal cell cancer that is at high risk for recurrence. The potential for leveraging what we have learned from these trials to conduct successful contemporary adjuvant and perioperative immune checkpoint inhibition trials and future adjuvant trial design is discussed...
October 29, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/30345423/adjuvant-antiangiogenic-agents-in-post-nephrectomy-renal-cell-carcinoma-a-systematic-review-and-meta-analysis
#4
Mohamad B Sonbol, Belal Firwana, Talal Hilal, Zhen Wang, Diana Almader-Douglas, Richard W Joseph, Thai H Ho
Context: The role of antiangiogenic agents in advanced renal cell carcinoma (RCC) is well established. However, it is still not clear whether this benefit can be extrapolated to the adjuvant setting. Objective: To determine the efficacy and safety of antiangiogenic agents in patients with RCC and a high risk of relapse after nephrectomy. Evidence acquisition: We searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials for randomized controlled trials (RCTs) evaluating the use of any oral antiangiogenic agent compared to placebo in post-nephrectomy RCC patients...
June 2018: European urology oncology
https://www.readbyqxmd.com/read/30187355/immune-checkpoint-inhibitors-toward-new-paradigms-in-renal-cell-carcinoma
#5
REVIEW
Ronan Flippot, Bernard Escudier, Laurence Albiges
Immune modulatory treatment regimens, led by immune checkpoint inhibitors, have transformed the treatment of clear-cell renal cell carcinoma. First-in-class, the PD-1 inhibitor nivolumab improved overall survival in advanced renal cell carcinoma following prior anti-angiogenic therapy, an important shift in the management of clear-cell renal cell carcinoma. Further improvements of long-term outcomes will be driven by combinations in the first-line setting, including PD-1/PD-L1 associated with antiangiogenic therapies, or PD1/PD-L1 inhibitors with other immune checkpoint inhibitors such as anti-CTLA-4, anti-LAG-3 or TIM-3 targeted therapies...
September 2018: Drugs
https://www.readbyqxmd.com/read/30148828/adjuvant-treatment-in-renal-cell-carcinoma
#6
REVIEW
Nazli Dizman, Jacob J Adashek, JoAnn Hsu, Paulo G Bergerot, Cristiane D Bergerot, Sumanta K Pal
In parallel with advances in the treatment of metastatic renal cell carcinoma (RCC), multiple adjuvant treatments have been tested for RCC. Adjuvant approaches now extend beyond conventional immunotherapies, such as interferon alfa and interleukins, to targeted therapies and immune checkpoint inhibitors. Most treatment approaches before the targeted treatment era did not improve patient outcomes, or study results were mixed. For example, a recent study found that disease-free survival was longer with sunitinib than with placebo in high-risk clear cell RCC, which led to the regulatory approval of sunitinib...
August 2018: Clinical Advances in Hematology & Oncology: H&O
https://www.readbyqxmd.com/read/30130544/patterns-of-relapse-and-implications-for-post-nephrectomy-surveillance-for-patients-with-high-risk-non-clear-cell-renal-cell-carcinoma-subgroup-analysis-of-the-phase-3-ecog-acrin-e2805-trial
#7
Vivek Narayan, Maneka Puligandla, Naomi B Haas, Pearl Subramanian, Robert S DiPaola, Robert Uzzo
PURPOSE: The natural history of non-clear cell renal cell carcinomas (non-ccRCC) following surgery with curative intent remains poorly defined, with post-operative surveillance informed by guidelines largely intended for clear cell RCC (ccRCC). We evaluated the patterns of relapse and potential implications for post-nephrectomy surveillance for patients with non-ccRCC enrolled in the largest randomized trial of adjuvant anti-angiogenic therapy for high-risk RCC (E2805). MATERIALS AND METHODS: This was a retrospective analysis of patients with completely resected non-ccRCC...
August 18, 2018: Journal of Urology
https://www.readbyqxmd.com/read/30116683/an-attempt-to-quantitate-value-in-medical-oncologic-therapy
#8
Christie Hancock, Linda Green, Timothy Lestingi, Jacob Bitran Md
Objective We wanted to examine the incremental cost-effective ratio (ICER) for a variety of Food and Drug Administration (FDA) approved oncology drugs in the adjuvant or curative setting to determine the value provided. Design We examined the annualized incremental drug costs of a variety of FDA approved chemotherapeutic drugs used in an adjuvant or curative setting based on National Comprehensive Cancer Network (NCCN) category 1 practice guidelines for melanoma, Her2/neu over-expressive breast cancer, renal cell carcinoma, stage IIIA non-small cell lung cancer, myeloma, B cell lymphoma, and Hodgkin lymphoma...
June 14, 2018: Curēus
https://www.readbyqxmd.com/read/29935800/developments-in-urologic-oncology-oncoforum-the-best-of-2017
#9
F Gómez-Veiga, A Alcaraz-Asensio, J Burgos-Revilla, J Cózar-Olmo
OBJECTIVE: To put forth new findings of urologic oncology with impact on clinical practice presented during 2017 in the main annual meetings. METHODS: This document reviews abstracts on prostate, kidney and bladder cancer presented at the congresses of 2016 (EAU, AUA, ASCO, ESMO and ASTRO) and publications with the highest impact in this period valued with the highest scores by the OncoForum committee. RESULTS: Among patients at high risk of recurrent renal cell carcinoma after nephrectomy, adjuvant sunitinib compared to placebo showed a benefit in patients at higher risk of recurrence...
October 2018: Actas Urologicas Españolas
https://www.readbyqxmd.com/read/29877179/kidney-cancer-research-network-of-canada-consensus-statement-on-the-role-of-adjuvant-therapy-after-nephrectomy-for-high-risk-non-metastatic-renal-cell-carcinoma-a-comprehensive-analysis-of-the-literature-and-meta-analysis-of-randomized-controlled-trials
#10
Pierre I Karakiewicz, Emanuele Zaffuto, Anil Kapoor, Naveen S Basappa, Georg A Bjarnason, Normand Blais, Rodney H Breau, Christina Canil, Darrel Drachenberg, Sebastien J Hotte, Claudio Jeldres, Michael A S Jewett, Wassim Kassouf, Christian Kollmannsberger, Luke T Lavallée, Ranjena Maloni, Francois Patenaude, Frédéric Pouliot, M Neil Reaume, Robert Sabbagh, Bobby Shayegan, Alan So, Denis Soulières, Simon Tanguay, Lori Wood, Marco Bandini
INTRODUCTION: The Kidney Cancer Research Network of Canada (KCRNC) collaborated to prepare this consensus statement about the use of target agents as adjuvant therapy in patients with non-metastatic renal cell carcinoma (nmRCC) after nephrectomy. We reviewed the published data and performed a meta-analysis of studies that focused on vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKIs). METHODS: A systematic literature search identified seven trials on adjuvant target therapy in nmRCC...
June 2018: Canadian Urological Association Journal, Journal de L'Association des Urologues du Canada
https://www.readbyqxmd.com/read/29868467/advances-and-challenges-on-management-of-gastrointestinal-stromal-tumors
#11
REVIEW
Lin Mei, Wei Du, Michael Idowu, Margaret von Mehren, Sosipatros A Boikos
Gastrointestinal stromal tumors (GISTs) originate from interstitial cells of Cajal and account for over 5,000 newly diagnosed cases in the United States. The discovery of activated KIT and PDGFRA mutations and introduction of imatinib revolutionized the treatment strategy and opened up the new era of target therapy for solid tumors. Although surgery remains the primary modality of treatment for curative purpose, almost half of the patients experienced disease recurrence. Tailoring (neo)-adjuvant treatment with imatinib is ongoing to meet the need for an effective therapy...
2018: Frontiers in Oncology
https://www.readbyqxmd.com/read/29784745/updates-to-the-management-of-kidney-cancer
#12
Eric Jonasch
Several updates were made to the 2018 NCCN Guidelines for Kidney Cancer. Adjuvant sunitinib is the first adjuvant therapy to be endorsed by the panel for patients with stage II and III clear cell histology renal cell carcinoma (RCC; category 2B). A promising new treatment-ipilimumab plus nivolumab for patients at intermediate and poor risk in the frontline setting-was added to the guidelines as well. Cabozantinib was added as a first-line option for poor- and intermediate-risk patients with advanced RCC.
May 2018: Journal of the National Comprehensive Cancer Network: JNCCN
https://www.readbyqxmd.com/read/29784193/adjuvant-vascular-endothelial-growth-factor-targeted-therapy-in-renal-cell-carcinoma-a-systematic-review-and-pooled-analysis
#13
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...
November 2018: European Urology
https://www.readbyqxmd.com/read/29773662/validation-of-the-16-gene-recurrence-score-in-patients-with-locoregional-high-risk-renal-cell-carcinoma-from-a-phase-iii-trial-of-adjuvant-sunitinib
#14
Brian I Rini, Bernard Escudier, Jean-Francois Martini, Ahmed Magheli, Christer Svedman, Margarita Lopatin, Dejan Knezevic, Audrey D Goddard, Phillip G Febbo, Rachel Li, Xun Lin, Olga Valota, Michael Staehler, Robert J Motzer, Alain Ravaud
Purpose: Adjuvant sunitinib prolonged disease-free survival (DFS; HR, 0.76) in patients with locoregional high-risk renal cell carcinoma (RCC) in the S-TRAC trial (ClinicalTrials.gov NCT00375674). The 16-gene Recurrence Score (RS) assay was previously developed and validated to estimate risk for disease recurrence in patients with RCC after nephrectomy. This analysis further validated the prognostic value of RS assay in patients from S-TRAC and explored the association of RS results with prediction of sunitinib benefit...
May 17, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29726794/ectopic-rhabdoid-meningioma-of-the-orbit-in-a-child-case-report-and-review-of-the-literature
#15
Yağmur Seda Yeşiltaş, Kaan Gündüz, Aylin Okçu Heper, Esra Erden
In August 2016, an 11-year-old boy presented to the authors' institution with a right orbital tumor that was located superotemporally (superolaterally) and adherent to the sclera. The patient's past medical history revealed that he had undergone 2 previous craniotomies elsewhere in June 2008 and July 2010 for a superomedially located orbital lesion that had been histopathologically diagnosed as a neurothekeoma. After the second craniotomy, the patient underwent adjuvant intensity modulated radiotherapy (IMRT) to the right medial orbit...
August 2018: Journal of Neurosurgery. Pediatrics
https://www.readbyqxmd.com/read/29662544/sunitinib-in-the-treatment-of-renal-cell-carcinoma-an-update-on-recent-evidence
#16
REVIEW
Mimma Rizzo, Camillo Porta
Sunitinib is a multitarget tyrosine kinase inhibitor endowed mainly by antiangiogenic effects, although an indirect inhibitory effect on tumor growth and, more recently, a complex activity on antitumor immune response has been described. From approval by the US Food and Drug Administration (FDA) in January 2006, sunitinib represents a key molecule in the treatment of metastatic renal cell carcinoma (mRCC) due to the peculiar molecular pathogenesis of this neoplasm. Over the past 10 years, clinical trials and real-world experiences helped clinicians to understand how, when and for how long to use sunitinib...
August 2017: Therapeutic Advances in Urology
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
#17
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...
April 2018: Future Oncology
https://www.readbyqxmd.com/read/29573266/sorafenib-paradoxically-activates-the-ras-raf-erk-pathway-in-polyclonal-human-nk-cells-during-expansion-and-thereby-enhances-effector-functions-in-a-dose-and-time-dependent-manner
#18
J Lohmeyer, T Nerreter, J Dotterweich, H Einsele, R Seggewiss-Bernhardt
Natural killer (NK) cells play a major role in host immunity against leukaemia and lymphoma. However, clinical trials applying NK cells have not been as efficient as hoped for. Patients treated with rapidly accelerated fibrosarcoma (RAF) inhibitors exhibit increased tumour infiltration by immune cells, suggesting that a combination of RAF inhibitors with immunotherapy might be beneficial. As mitogen-activated protein kinases (MAPKs) such as raf-1 proto-oncogene, serine/threonine kinase (CRAF) regulate NK cell functions, we performed an in-vitro investigation on the potential of clinically relevant short-acting tyrosine kinase inhibitors (TKIs) as potential adjuvants for NK cell therapy: NK cells from healthy human blood donors were thus treated with sorafenib, sunitinib or the pan-RAF inhibitor ZM336372 during ex-vivo expansion...
July 2018: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/29522146/the-us-food-and-drug-administration-s-approval-of-adjuvant-sunitinib-for-renal-cell-cancer-a-case-of-regulatory-capture
#19
Bishal Gyawali, Daniel A Goldstein
No abstract text is available yet for this article.
May 1, 2018: JAMA Oncology
https://www.readbyqxmd.com/read/29507530/the-tyrosine-kinase-inhibitor-nilotinib-is-more-efficient-than-mitotane-in-decreasing-cell-viability-in-spheroids-prepared-from-adrenocortical-carcinoma-cells
#20
Elaine Silveira, Isadora Pontes Cavalcante, Jean Lucas Kremer, Pedro Omori Ribeiro de Mendonça, Claudimara Ferini Pacicco Lotfi
Background: New drugs for adrenocortical carcinoma (ACC) are needed because most patients undergo rapid disease progression despite surgery and adjuvant therapy with mitotane. In this study, we aimed to investigate the in vitro effects of different chemotherapy drugs, alone or combined with mitotane, on the viability of adrenocortical carcinoma cells. Methods: Everolimus, sunitinib, zoledronic acid, imatinib and nilotinib cytotoxicity, alone or combined with mitotane were tested on ACC H295R cells in monolayer or spheroid cultures using MTS assays and confocal microscopy...
2018: Cancer Cell International
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