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https://www.readbyqxmd.com/read/28808717/the-opening-closure-of-the-p-loop-and-hinge-of-bcr-abl1-decodes-the-low-high-bioactivities-of-dasatinib-and-axitinib
#1
Jianyi Wang, Qing Chen, Mian Wang, Cheng Zhong
To obtain new insights into the resistance caused by T315I and the differential selectivities of dasatinib and axitinib against BCR-ABL1(WT) and BCR-ABL1(T315), molecular dynamics simulations and free energy calculations were performed. A rule is summarized that the opening/closure of the P-loop and hinge of BCR-ABL1 could reflect the low/high bioactivities of dasatinib and axitinib. This may be because strong interactions of the ligands with key residues induce the P-loop and hinge of BCR-ABL1 to close, being favorable for the retention of the ligand in the binding site...
August 15, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/28807653/the-effects-of-neoadjuvant-axitinib-on-anthropometric-parameters-n-patients-with-locally-advanced-non-metastatic-renal-cell-carcinoma
#2
Shivashankar Damodaran, E Jason Abel
No abstract text is available yet for this article.
August 11, 2017: Urology
https://www.readbyqxmd.com/read/28761748/new-treatment-options-for-metastatic-renal-cell-carcinoma
#3
REVIEW
Alejo Rodriguez-Vida, Thomas E Hutson, Joaquim Bellmunt, Michiel H Strijbos
During the last decade, the treatment of advanced or metastatic renal cell carcinoma (RCC) was revolutionised with the advent of antiangiogenic drugs and tyrosine-kinase inhibitors. Several agents targeting the vascular endothelial growth factor (VEGF) pathway (sunitinib, bevacizumab, pazopanib, axitinib) or the mammalian target of rapamycin pathway (temsirolimus, everolimus) were since then progressively approved for first-line or later-line use in the treatment of patients with advanced RCC and became the new standard of care...
2017: ESMO Open
https://www.readbyqxmd.com/read/28752352/presurgical-axitinib-therapy-increases-fibrotic-reactions-within-tumor-thrombus-in-renal-cell-carcinoma-with-thrombus-extending-to-the-inferior-vena-cava
#4
Yoshimi Tanaka, Shingo Hatakeyama, Shogo Hosogoe, Toshikazu Tanaka, Itsuto Hamano, Ayumu Kusaka, Hiromich Iwamura, Naoki Fujita, Hayato Yamamoto, Yuki Tobisawa, Tohru Yoneyama, Takahiro Yoneyama, Yasuhiro Hashimoto, Takuya Koie, Chikara Ohyama
BACKGROUND: Clinical benefits of presurgical axitinib therapy for renal cell carcinoma (RCC) extending into the inferior vena cava (IVC) remain unclear. We aimed to investigate surgical benefits and pathological antitumor effects of presurgical axitinib therapy for RCC with IVC thrombus. METHODS: Of 56 consecutive RCC patients with IVC thrombus between January 1994 and December 2016, 41 patients who underwent radical nephrectomy (RN) were categorized as upfront RN (Upfront group) or presurgical axitinib followed by RN (Presurgical group)...
July 27, 2017: International Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28748721/real-world-costs-and-outcomes-in-metastatic-renal-cell-carcinoma-patients-treated-with-targeted-therapies-a-cohort-study-from-the-french-health-insurance-database
#5
Rana Maroun, Laetitia Fleury, Gaelle Nachbaur, Franck Maunoury, Jean-Louis Vanhille, Isabelle Durand-Zaleski
OBJECTIVES: The objective of this study was to describe treatment patterns, survival, healthcare use and costs in patients with metastatic renal cell carcinoma (mRCC) in a real-world setting. RESEARCH DESIGN AND METHODS: We used the National Health Insurance (NHI) claims database for the Ile-de-France region to perform a retrospective cohort analysis of patients with mRCC treated by a first-line targeted therapy. Treatment naïve patients were identified combining the 10th revision of the International Classification of Diseases (ICD-10) codes (C64 & C77-C79) and a first prescription of targeted therapies...
August 7, 2017: Current Medical Research and Opinion
https://www.readbyqxmd.com/read/28733794/fatigue-associated-with-newly-approved-vascular-endothelial-growth-factor-receptor-tyrosine-kinase-inhibitors-in-cancer-patients-an-up-to-date-meta-analysis
#6
REVIEW
Jing Li, Jian Gu
The fatigue associated with five newly approved vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs) (regorafenib, vandetanib, cabozantinib, lenvatinib, axitinib) is poorly understood. We conducted this systematic review to fully investigate the fatigue associated with these VEGFR-TKIs in cancer patients. Relevant studies of randomized controlled trials in cancer patients treated with the five VEGFR-TKIs were retrieved and a systematic evaluation was conducted. EMBASE, MEDLINE, and PubMed were searched for articles published until March 2017...
July 21, 2017: International Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28732453/real-world-chart-review-study-of-adverse-events-management-in-patients-taking-tyrosine-kinase-inhibitors-to-treat-metastatic-renal-cell-carcinoma
#7
Sandy Srinivas, Dara Stein, Dana Y Teltsch, Sunning Tao, Laura Cisar, Krishnan Ramaswamy
Purpose The purpose is to describe management of adverse events of special interest across tyrosine kinase inhibitors approved for metastatic renal cell carcinoma. Methods We conducted a retrospective chart review in metastatic renal cell carcinoma patients initiating tyrosine kinase inhibitor monotherapy between 15 November 2010 and 15 November 2013, and experiencing ≥ 1 adverse events of special interest (diarrhea, fatigue, hand-foot syndrome, hypertension, or stomatitis/mucositis) within 3 months of initiation...
January 1, 2017: Journal of Oncology Pharmacy Practice
https://www.readbyqxmd.com/read/28710508/risk-of-gastrointestinal-events-with-newly-approved-after-2011-vascular-endothelial-growth-factor-receptor-tyrosine-kinase-inhibitors-in-cancer-patients-a-meta-analysis-of-randomized-controlled-trials
#8
REVIEW
Jing Li, Jian Gu
PURPOSE: We performed a meta-analysis to systematically review the gastrointestinal (GI) events (diarrhea, nausea, vomiting, anorexia) of five newly approved (after 2011) VEGFR-TKIs in cancer patients. METHODS: The relevant studies of the randomized controlled trials (RCTs) in cancer patients treated with cabozantinib, vandetanib, lenvatinib, regorafenib, and axitinib were retrieved and the systematic evaluation was conducted. RESULTS: Forty-one randomized controlled trials and 10,860 patients were included...
July 15, 2017: European Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28707479/axitinib-in-metastatic-renal-cell-carcinoma-beyond-the-second-line-setting
#9
Yoshiko Umeyama, Yoshiyuki Shibasaki, Hideyuki Akaza
Treatment options for advanced and metastatic renal cell carcinoma have advanced considerably in the past decade with the approval of several targeted agents, including axitinib. Axitinib is a potent and selective inhibitor of VEGFRs 1-3, and is well established as second-line treatment. This article summarizes factors to be considered when administering axitinib, such as individualized dose titration and axitinib-associated adverse events, in order to retain patients longer on treatment, which would likely lead to improved efficacy outcomes...
July 14, 2017: Future Oncology
https://www.readbyqxmd.com/read/28706336/palmoplantar-exfoliation-due-to-chloroquine
#10
Pragya Ashok Nair, Trusha Patel
Chloroquine is the drug very frequently used for the treatment of malaria. It is also used in amebiasis, rheumatoid arthritis, and various dermatological conditions. Chloroquine can cause muscle problems, loss of appetite, and diarrhea as a side effect. Cutaneous toxicity includes pruritus, hair loss, photosensitivity, and color changes. Exfoliation of skin over palms and soles is caused by chemotherapeutic drugs such as axitinib, fluorouracil, idarubicin, doxorubicin, sunitinib, sorafenib, and paclitaxel. Here, a case of a 40-year-old female is presented who developed palmoplantar exfoliation with depigmentation after taking chloroquine...
March 2017: Indian Journal of Pharmacology
https://www.readbyqxmd.com/read/28705573/the-effects-of-neoadjuvant-axitinib-on-anthropometric-parameters-in-patients-with-locally-advanced-non-metastatic-renal-cell-carcinoma
#11
Lisly Chéry, Leonardo D Borregales, Bryan Fellman, Diana L Urbauer, Naveen Garg, Nathan Parker, Matthew H G Katz, Christopher G Wood, Jose A Karam
OBJECTIVE: To examine the effect that neoadjuvant axitinib for the treatment of localized renal cell carcinoma has on body compartment composition. PATIENTS AND METHODS: The study was based on a single-institution, single-arm clinical trial that enrolled 24 patients with locally advanced non-metastatic biopsy-proven clear cell renal cell carcinoma. Patients received axitinib orally for up to 12 weeks. Computed tomography scans were completed before the start of treatment, after 7 weeks of treatment and at the completion of 12 weeks of treatment...
July 10, 2017: Urology
https://www.readbyqxmd.com/read/28687563/axitinib-treatment-in-advanced-rai-resistant-differentiated-thyroid-cancer-dtc-and-refractory-medullary-thyroid-cancer-mtc
#12
Jaume Capdevila, Jose Manuel Trigo, Javier Aller, Jose Luis Manzano, Silvia Garcia-Adrian, Carles Zafon, Oscar Reig, Uriel Bohn, Teresa Ramon Y Cajal, Manuel Duran, Beatriz Gonzalez-Astorga, Ana Lopez-Alfonso, Javier Medina, Ignacio Porras, Juan Jose Reina, Nuria Palacios, Enrique Grande, Elena Cillan, Ignacio Matos, Juan Jose Grau
BACKGROUND: Axitinib, an antiangiogenic multikinase inhibitor (MKI) was evaluated in the compassionate-use-program in Spain (October 2012-November 2014). MATERIALS AND METHODS: 47 patients with advanced radioactive iodine-refractory differentiated thyroid cancer (DTC, n=34) or medullary thyroid cancer (MTC, n=13) with documented disease progression were treated with axitinib 5 mg bid. The primary efficacy endpoint was overall response rate (ORR) by RECIST v1.1. Progression-free survival (PFS) and adverse events (AEs) were secondary objectives...
July 7, 2017: European Journal of Endocrinology
https://www.readbyqxmd.com/read/28668864/axitinib-for-gemcitabine-refractory-advanced-biliary-tract-cancer-report-of-5-cases
#13
Naohiro Okano, Akiyoshi Kasuga, Kirio Kawai, Takaaki Kobayashi, Daisuke Naruge, Fumio Nagashima, Junji Furuse
BACKGROUND/AIM: Vascular endothelial growth factor receptor (VEGFR) has been identified as a treatment target for biliary tract cancer (BTC) and axitinib is a selective inhibitor of vascular endothelial growth factor receptor (VEGFR)-1/2/3. This study was conducted as a preliminary evaluation of the safety and efficacy of axitinib for patients with advanced BTC. PATIENTS AND METHODS: Patients refractory to gemcitabine-based regimens were administered axitinib at the dose of 5 mg twice daily...
July 2017: Anticancer Research
https://www.readbyqxmd.com/read/28645482/proton-pump-inhibitors-and-survival-outcomes-in-patients-with-metastatic-renal-cell-carcinoma
#14
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
#15
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
#16
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...
September 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
#17
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
#18
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)...
July 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28561652/evolving-treatment-paradigm-in-metastatic-renal-cell-carcinoma
#19
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
#20
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...
July 25, 2017: Oncotarget
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