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https://www.readbyqxmd.com/read/28645482/proton-pump-inhibitors-and-survival-outcomes-in-patients-with-metastatic-renal-cell-carcinoma
#1
Aly-Khan A Lalani, Rana R McKay, Xun Lin, Ronit Simantov, Marina D Kaymakcalan, Toni K Choueiri
INTRODUCTION: Proton pump inhibitors (PPIs) are potent inhibitors of gastric acid secretion and can affect the optimal absorption of concomitant oral medications, such as vascular endothelial growth factor (VEGF) tyrosine kinase inhibitors (TKIs). The purpose of this study was to investigate the effect of PPI use on survival in metastatic renal cell carcinoma (mRCC) patients treated in the targeted therapy era. MATERIALS AND METHODS: We conducted a pooled analysis of mRCC patients treated in phase II and III clinical trials...
May 31, 2017: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/28640364/a-phase-2-study-of-the-efficacy-and-biomarker-on-the-combination-of-transarterial-chemoembolization-and-axitinib-in-the-treatment-of-inoperable-hepatocellular-carcinoma
#2
Stephen L Chan, Winnie Yeo, Frankie Mo, Anthony W H Chan, Jane Koh, Leung Li, Edwin P Hui, Charing C N Chong, Paul B S Lai, Tony S K Mok, Simon C H Yu
BACKGROUND: A surge of vascular endothelial growth factor (VEGF) after transarterial chemoembolization (TACE) may contribute to tumor progression. Axitinib is a potent antiangiogenic agent with main activity against VEGF receptors 1 to 3. To the authors' knowledge, its role in combination with TACE for the treatment of patients with inoperable hepatocellular carcinoma (HCC) is unclear. METHODS: A phase 2 clinical trial (ClinicalTrials.gov identifier NCT01352728) was conducted to evaluate the combination treatment...
June 22, 2017: Cancer
https://www.readbyqxmd.com/read/28590313/current-management-of-metastatic-renal-cell-carcinoma-evolving-new-therapies
#3
Ravi Kumar, Anil Kapoor
PURPOSE OF REVIEW: Targeted therapies have recently replaced cytokine treatments as the gold standard for management of metastatic renal cell carcinoma (mRCC). Currently approved treatments include the tyrosine kinase inhibitors sunitinib, pazopanib, axitinib, sorafenib, cabozantinib and lenvatinib; the vascular endothelial growth factor (VEGF) inhibitor bevacizumab; the mammalian target of rapamycin (mTOR) inhibitors everolimus and temsirolimus; and the immunologic nivolumab. The purpose of this review is to provide an updated analysis of the clinical data supporting the use of these agents in the first-line and second-line setting...
June 5, 2017: Current Opinion in Supportive and Palliative Care
https://www.readbyqxmd.com/read/28579443/value-based-pricing-and-the-end-of-pharmaceutical-pricing-as-we-know-it-a-case-study-on-sorafenib-and-axitinib
#4
EDITORIAL
Panagiotis Petrou
No abstract text is available yet for this article.
June 1, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28572534/contrast-media-enhancement-reduction-predicts-tumor-response-to-presurgical-molecular-targeting-therapy-in-patients-with-advanced-renal-cell-carcinoma
#5
Shogo Hosogoe, Shingo Hatakeyama, Ayumu Kusaka, Itsuto Hamano, Yoshimi Tanaka, Kazuhisa Hagiwara, Hideaki Hirai, Satoko Morohashi, Hiroshi Kijima, Hayato Yamamoto, Yuki Tobisawa, Tohru Yoneyama, Takahiro Yoneyama, Yasuhiro Hashimoto, Takuya Koie, Chikara Ohyama
BACKGROUND AND OBJECTIVE: A quantitative tumor response evaluation to molecular-targeting agents in advanced renal cell carcinoma (RCC) is debatable. We aimed to evaluate the relationship between radiologic tumor response and pathological response in patients with advanced RCC who underwent presurgical therapy. RESULTS: Of 34 patients, 31 underwent scheduled radical nephrectomy. Presurgical therapy agents included axitinib (n = 26), everolimus (n = 3), sunitinib (n = 1), and axitinib followed by temsirolimus (n = 1)...
May 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28561652/evolving-treatment-paradigm-in-metastatic-renal-cell-carcinoma
#6
David M Gill, Neeraj Agarwal, Ulka Vaishampayan
The treatment paradigm for advanced and metastatic renal cell carcinoma (mRCC) has evolved rapidly since the arrival of targeted therapies and novel immunotherapies. mRCC was previously treated only with cytokines. However, discoveries of mutations affecting the von Hippel-Lindau tumor suppressor gene (leading to increased expression of VEGF and hypoxia inducible factor/HIF-1) and of deregulations in the phosphatidylinositol-3 kinase/AKT/mTOR pathway (resulting in tumor angiogenesis, cell proliferation, and tumor growth) have led to the development of numerous targeted therapies...
2017: American Society of Clinical Oncology Educational Book
https://www.readbyqxmd.com/read/28548943/intra-tumour-molecular-heterogeneity-of-clear-cell-renal-cell-carcinoma-reveals-the-diversity-of-the-response-to-targeted-therapies-using-patient-derived-xenograft-models
#7
Baoan Hong, Yong Yang, Sheng Guo, Shayiremu Duoerkun, Xiaohu Deng, Dawei Chen, Shijun Yu, Wubin Qian, Qixiang Li, Qing Li, Kan Gong, Ning Zhang
Inter- and intra-tumour molecular heterogeneity is increasingly recognized in clear cell renal cell carcinoma (ccRCC). It may partially explain the diversity of responses to targeted therapies and the various clinical outcomes. In this study, a 56-year-old male ccRCC patient with multiple metastases received radical nephrectomy and resection of the metastatic tumour in chest wall. The surgical specimens were implanted into nude mice to establish patient-derived xenograft (PDX) models with KI2367 model derived from the primary tumour and KI2368 model from the metastastic tumour...
May 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28544544/insulin-like-growth-factor-1-signaling-is-responsible-for-cathepsin-g-induced-aggregation-of-breast-cancer-mcf-7-cells
#8
Riyo Morimoto-Kamata, Satoru Yui
Cathepsin G (CG), a neutrophil serine protease, induces cell migration and multicellular aggregation of human breast cancer MCF-7 cells in a process that is dependent on E-cadherin and CG enzymatic activity. While these tumor cell aggregates can cause tumor emboli that could represent intravascular growth and extravasation into the surrounding tissues, resulting in metastasis, the molecular mechanism underlying this process remains poorly characterized. In this study, we aimed to identify the signaling pathway that is triggered during CG-mediated stimulation of cell aggregation...
May 24, 2017: Cancer Science
https://www.readbyqxmd.com/read/28532444/haemoglobin-level-increase-as-an-efficacy-biomarker-during-axitinib-treatment-for-metastatic-renal-cell-carcinoma-a-retrospective-study
#9
Alison C Johnson, Margarida Matias, Helen Boyle, Bernard Escudier, Alicia Molinier, Brigitte Laguerre, Carole Helissey, Pierre-Emmanuel Brachet, Audrey Emmanuelle Dugué, Loic Mourey, Elodie Coquan, Florence Joly
BACKGROUND: Axitinib is used after failure of first line treatment for metastatic renal cell carcinoma (mRCC). A known side effect is the increase of haemoglobin level (HbL) during treatment with a suspected correlation with better outcome. Our objective was to examine whether HbL increase during the first three months of axitinib treatment is associated with better prognosis. METHODS: Retrospective multicentre analysis including patients with mRCC treated with axitinib for at least three months from 2012 to 2014...
May 22, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28511146/real-world-prospective-experience-of-axitinib-in-metastatic-renal-cell-carcinoma%C3%A2-in-a-large-comprehensive-cancer-centre
#10
Margarida Matias, Gwénaël Le Teuff, Laurence Albiges, Annalisa Guida, Caroline Brard, Giulia Bacciarelo, Yohann Loriot, Christophe Massard, Nathalie Lassau, Karim Fizazi, Bernard Escudier
BACKGROUND: Axitinib has shown activity in metastatic renal cell carcinoma (mRCC) in a large phase III clinical trial and was approved in patients who failed first-line therapy. This drug has been available in France since November 2012. The objective is to report efficacy and safety of axitinib in mRCC outside of clinical trials. METHODS: A prospective evaluation of mRCC patients treated by axitinib in second or further next-line therapy at Gustave Roussy was conducted from 2012 to 2015...
May 13, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28485672/axitinib-in-metastatic-renal-cell-carcinoma-patient-characteristics-and-treatment-patterns-in-us-community-oncology-centers
#11
Thomas E Hutson, Xiaolong Jiao, Thomas Wilson, Laura Cisar, Elizabeth A MacLean
AIM: To study patient characteristics and treatment patterns in real-world axitinib use for metastatic renal cell carcinoma. PATIENTS & METHODS: We conducted a retrospective analysis of second- or third-line axitinib use between 1 January 2012 and 31 October 2014 in 135 metastatic renal cell carcinoma patients using the US Oncology Network database. RESULTS: Overall, 86.7% had clear cell histology, 57.8% had stage III/IV disease at diagnosis and 55...
May 9, 2017: Future Oncology
https://www.readbyqxmd.com/read/28475010/computational-analysis-of-abl-kinase-mutations-allows-predicting-drug-sensitivity-against-selective-kinase-inhibitors
#12
Swapna Kamasani, Sravani Akula, Sree Kanth Sivan, Vijjulatha Manga, Justus Duyster, Dashavantha Reddy Vudem, Rama Krishna Kancha
The ABL kinase inhibitor imatinib has been used as front-line therapy for Philadelphia-positive chronic myeloid leukemia. However, a significant proportion of imatinib-treated patients relapse due to occurrence of mutations in the ABL kinase domain. Although inhibitor sensitivity for a set of mutations was reported, the role of less frequent ABL kinase mutations in drug sensitivity/resistance is not known. Moreover, recent reports indicate distinct resistance profiles for second-generation ABL inhibitors. We thus employed a computational approach to predict drug sensitivity of 234 point mutations that were reported in chronic myeloid leukemia patients...
May 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28451830/hemodialysis-does-not-impact-axitinib-exposure-clinical-case-of-a-patient-with-metastatic-renal-cell-carcinoma
#13
Antoine Thiery-Vuillemin, Emeline Orillard, Guillaume Mouillet, Fabien Calcagno, Nadège Devillard, Stéphane Bouchet, Bernard Royer
Axitinib is approved with indication in patients with advanced renal cell carcinoma (RCC). Due to the localization of this cancer, physicians sometimes have to deal with hemodialyzed patients. Data exploring hemodialysis (HD) impact on axitinib pharmacokinetic (PK) or safety are lacking. To date, no data have been published on that problematic. This is the first publication discussing the assessment of axitinib PK for a patient undergoing HD. Our results suggest that there is no influence of HD on axitinib blood concentration...
June 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28451413/a-case-of-metastatic-xp11-2-translocation-renal-cell-carcinoma-successfully-managed-by-cytoreductive-nephrectomy-followed-by-axitinib-therapy
#14
Koichi Nishimura, Toshio Takagi, Naohiro Toda, Tomoko Yamamoto, Tsunenori Kondo, Hideki Ishida, Yoji Nagashima, Kazunari Tanabe
Targeted medications for metastatic adult Xp11.2 translocation renal cell carcinoma (RCC) remain to be identified. We herein report a case of metastatic Xp11.2 translocation RCC controlled with cytoreductive nephrectomy (CN) and axitinib therapy. A 57-year-old woman complained of fatigue and low back pain. Imaging studies revealed a right renal tumor, with multiple lung and mediastinal lymph node metastases. Although the patient received 10 mg axitinib therapy for 5 months at the hospital she was initially admitted to, the size of the primary and metastatic lesions was not reduced...
March 2017: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/28439491/translating-new-data-to-the-daily-practice-in-second-line-treatment-of-renal-cell-carcinoma-the-role-of-tumor-growth-rate
#15
EDITORIAL
Enrique Grande, Olga Martínez-Sáez, Pablo Gajate-Borau, Teresa Alonso-Gordoa
The therapeutic options for patients with metastatic renal cell carcinoma (mRCC) have completely changed during the last ten years. With the sequential use of targeted therapies, median overall survival has increased in daily practice and now it is not uncommon to see patients surviving kidney cancer for more than four to five years. Once treatment fails with the first line targeted therapy, head to head comparisons have shown that cabozantinib, nivolumab and the combination of lenvatinib plus everolimus are more effective than everolimus alone and that axitinib is more active than sorafenib...
April 10, 2017: World Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28426267/a-phase-2-trial-of-single-agent-axitinib-as-maintenance-therapy-following-first-line-treatment-with-modified-folfox-bevacizumab-in-patients-with-metastatic-colorectal-cancer
#16
Johanna C Bendell, Mathew Joseph, Kirk Barnes, Mark Mainwaring, Dianna Shipley, Chandra Reddy, Laura Blakely, Ronald Blachly, Cassie M Lane, Chris Earwood, Michel Kuzur
This phase-2 trial evaluated the efficacy of axitinib as maintenance therapy for patients with metastatic colorectal cancer (mCRC) following first-line treatment with FOLFOX/bevacizumab. Patients with mCRC received mFOLFOX/bevacizumab followed by axitinib maintenance after four cycles. The primary endpoint was progression-free survival (PFS). Seventy patients were enrolled. Common treatment-related toxicities were fatigue, nausea, diarrhea, and peripheral neuropathy during FOLFOX/bevacizumab treatment; and fatigue, hypertension, diarrhea, and peripheral neuropathy during axitinib treatment...
April 20, 2017: Cancer Investigation
https://www.readbyqxmd.com/read/28413127/evolution-of-circulating-tumor-dna-profile-from-first-line-to-subsequent-therapy-in-metastatic-renal-cell-carcinoma
#17
Sumanta K Pal, Guru Sonpavde, Neeraj Agarwal, Nicholas J Vogelzang, Sandy Srinivas, Naomi B Haas, Sabina Signoretti, Bradley A McGregor, Jeremy Jones, Richard B Lanman, Kimberly C Banks, Toni K Choueiri
BACKGROUND: Treatment of metastatic renal cell carcinoma (mRCC) typically entails mechanistically distinct agents across the first- and second-line setting. Activity of these agents may be predicated on selective pressure that modulates RCC biology. Circulating tumor DNA (ctDNA) is a platform to noninvasively ascertain temporal changes in genomic profile. OBJECTIVE: To assess the ctDNA profile in a large cohort of mRCC patients, and to assess changes across patients receiving first-line and later lines of therapy...
April 13, 2017: European Urology
https://www.readbyqxmd.com/read/28403496/-interdisciplinary-recommendations-for-the-treatment-of-metastatic-renal-cell-carcinoma
#18
Kurt Miller, Lothar Bergmann, Christian Doehn, Jürgen Gschwend, Ulrich Keilholz
Thanks to the use of targeted therapies, the prognosis of patients with metastatic renal cell carcinoma (mRCC) has improved significantly. A median overall survival of more than 2 years is a realistic claim. These improvements are also reflected in recent discussions about 3 and more lines of therapy.Sunitinib, pazopanib, the combination of bevacizumab and interferon alpha, and temsirolimus are approved for first-line therapy of mRCC. Sunitinib and pazopanib are also approved for second-line therapy, which, for pazopanib, is confined to the use after cytokine failure...
February 2017: Aktuelle Urologie
https://www.readbyqxmd.com/read/28388255/boosting-axitinib-exposure-with-a-cyp3a4-inhibitor-making-axitinib-treatment-personal
#19
Floor J E Lubberman, Nielka P van Erp, Rob Ter Heine, Carla M L van Herpen
No abstract text is available yet for this article.
April 7, 2017: Acta Oncologica
https://www.readbyqxmd.com/read/28378918/a-pharmacometric-framework-for-axitinib-exposure-efficacy-and-safety-in-metastatic-renal-cell-carcinoma-patients
#20
Emilie Schindler, Michael A Amantea, Mats O Karlsson, Lena E Friberg
The relationships between exposure, biomarkers (vascular endothelial growth factor (VEGF), soluble VEGF receptors (sVEGFR)-1, 2, 3, and soluble stem cell factor receptor (sKIT)), tumor sum of longest diameters (SLD), diastolic blood pressure (dBP) and overall survival (OS) were investigated in a modeling framework. The dataset included 64 metastatic renal cell carcinoma patients (mRCC) treated with oral axitinib. Biomarker time-courses were described by indirect response (IDR) models where axitinib inhibits sVEGFR-1, 2 and 3 production, and VEGF degradation...
April 5, 2017: CPT: Pharmacometrics & Systems Pharmacology
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