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Hiroto Matsuda, Satoshi Tamada, Minoru Kato, Akira Yamamoto, Taro Iguchi, Tatsuya Nakatani
A 73-year-old woman with chief complaint of macroscopic hematuria was diagnosed as having left renal tumor with pancreatic invasion. Nephrectomy was performed. Pathological diagnosis was clear cell carcinoma, pT3a. Three months after the operation, liver metastasis appeared and sunitinib was started. Most of the liver metastases disappeared; however, a new lesion appeared, and sunitinib was switched to axitinib, which was effective on the residual lesion, but the new lesion had poor response. Transarterial chemoembolization was performed to treat the liver metastases, and all metastatic lesions disappeared...
March 2018: Urology Case Reports
Yousef Zakharia, Arup Bhattacharya, Youcef M Rustum
Selenium (Se)-containing molecules exert antioxidant properties and modulate targets associated with tumor growth, metastasis, angiogenesis, and drug resistance. Prevention clinical trials with low-dose supplementation of different types of Se molecules have yielded conflicting results. Utilizing several xenograft models, we earlier reported that the enhanced antitumor activity of various chemotherapeutic agents by selenomethione and Se-methylselenocysteine in several human tumor xenografts is highly dose- and schedule-dependent...
February 13, 2018: Oncotarget
Toni K Choueiri, James Larkin, Mototsugu Oya, Fiona Thistlethwaite, Marcella Martignoni, Paul Nathan, Thomas Powles, David McDermott, Paul B Robbins, David D Chism, Daniel Cho, Michael B Atkins, Michael S Gordon, Sumati Gupta, Hirotsugu Uemura, Yoshihiko Tomita, Anna Compagnoni, Camilla Fowst, Alessandra di Pietro, Brian I Rini
BACKGROUND: The combination of an immune checkpoint inhibitor and a VEGF pathway inhibitor to treat patients with advanced renal-cell carcinoma might increase the clinical benefit of these drugs compared with their use alone. Here, we report preliminary results for the combination of avelumab, an IgG1 monoclonal antibody against the programmed cell death protein ligand PD-L1, and axitinib, a VEGF receptor inhibitor approved for second-line treatment of advanced renal-cell carcinoma, in treatment-naive patients with advanced renal-cell carcinoma...
March 9, 2018: Lancet Oncology
Ryoma Igarashi, Takamitsu Inoue, Nobuhiro Fujiyama, Norihiko Tsuchiya, Kazuyuki Numakura, Hideaki Kagaya, Mitsuru Saito, Shintaro Narita, Shigeru Satoh, Takenori Niioka, Masatomo Miura, Tomonori Habuchi
Axitinib is a potent second-line molecular-targeted agent for metastatic renal cell carcinoma (mRCC). Axitinib pharmacokinetics and its relation with genetic polymorphisms were evaluated to predict the adverse events (AEs) and efficacy of axitinib. We analyzed 46 patients with mRCC who were treated with axitinib. The plasma axitinib level was measured at 0, 2, 4, 8, and 12 h after administration (C0 , C2 , C4 , C8 , and C12 ; ng/mL) on day 7 of the treatment. Genetic polymorphisms related to axitinib pharmacokinetics, including SLCO1B1, SLCO1B3, SLCO2B1, ABCB1, ABCG2, CYP2C19, CYP3A5, and UGT1A1, were analyzed...
March 9, 2018: Medical Oncology
Ying-Ying Zhang, Naitee Ting
When Phase III treatment effect is diluted from what was observed from Phase II results, we propose to determine the Bayesian sample size for a Phase III clinical trial based on the normal, uniform, and truncated normal prior distributions of the treatment effects on an interval, which starts from an acceptable treatment effect to the observed treatment effect from Phase II. After incorporating the prior information of the treatment effects, the Bayesian sample size is the number of patients of the Phase III trial for a given Bayesian Predictive Power (BPP) or Bayesian Historical Predictive Power (BHPP)...
March 7, 2018: Journal of Biopharmaceutical Statistics
Heinz Läubli, Philipp Müller, Lucia D'Amico, Mélanie Buchi, Abhishek S Kashyap, Alfred Zippelius
Cancer immunotherapies have significantly improved the prognosis of cancer patients. Despite the clinical success of targeting inhibitory checkpoint receptors, including PD-1 and/or CTLA-4 on T cells, only a minority of patients derive benefit from these therapies. New strategies to improve cancer immunotherapy are therefore needed. Combination therapy of checkpoint inhibitors with targeted agents has promisingly shown to increase the efficacy of immunotherapy. Here, we analyzed the immunomodulatory effects of the multi-receptor tyrosine kinase inhibitor axitinib and its efficacy in combination with immunotherapies...
February 27, 2018: Cancer Immunology, Immunotherapy: CII
(no author information available yet)
Axitinib plus pembrolizumab has a 73% response rate in previously untreated advanced renal cell carcinoma.
February 23, 2018: Cancer Discovery
Michael B Atkins, Elizabeth R Plimack, Igor Puzanov, Mayer N Fishman, David F McDermott, Daniel C Cho, Ulka Vaishampayan, Saby George, Thomas E Olencki, Jamal C Tarazi, Brad Rosbrook, Kathrine C Fernandez, Mariajose Lechuga, Toni K Choueiri
BACKGROUND: Previous studies combining PD-1 checkpoint inhibitors with tyrosine kinase inhibitors of the VEGF pathway have been characterised by excess toxicity, precluding further development. We hypothesised that axitinib, a more selective VEGF inhibitor than others previously tested, could be combined safely with pembrolizumab (anti-PD-1) and yield antitumour activity in patients with treatment-naive advanced renal cell carcinoma. METHODS: In this ongoing, open-label, phase 1b study, which was done at ten centres in the USA, we enrolled patients aged 18 years or older who had advanced renal cell carcinoma (predominantly clear cell subtype) with their primary tumour resected, and at least one measureable lesion, Eastern Cooperative Oncology Group performance status 0-1, controlled hypertension, and no previous systemic therapy for renal cell carcinoma...
February 9, 2018: Lancet Oncology
Rongrui Wei, Qinge Ma, Tao Li, Wenmin Liu, Zhipei Sang, Mingbo Li, Saimei Liu
Two new carbazole alkaloids 1 and 2, and eleven known congeners 3-13 were isolated and identified from Clausena sanki for the first time. Their structures were elucidated on the basis of extensive UV, IR, MS, NMR spectroscopic data and comparison with literatures. The compounds 1-13 were evaluated by MTT assay to determine whether they decreased VEGF-mediated cell proliferation in HUVECs with Axitinib as positive control. Among them, compounds 1, 2, 6, 8, and 13 (μM) exhibited moderate antiangiogenic activities, which inhibited VEGF-induced HUVEC proliferation in vitro with IC50 values of 12...
January 31, 2018: Bioorganic Chemistry
Robert D Barrows, Kristin M Blacklock, Paul R Rablen, Sagar D Khare, Spencer Knapp
Replacement of the sulfur atom in biologically active diaryl and heteroaryl thioethers (Ar-S-Ar', HAr-S-Ar, and HAr-S-HAr') with any of several one-atom or two-atom linkers can be expected to reduce the susceptibility of the analogue to metabolic oxidation, a well-documented problem for thioethers intended for medicinal chemistry applications. Ab initio calculations indicate how well various proposed thioether isosteric groups, including some new and unusual ones, may perform structurally and electronically in replacing the bridging sulfur atom...
February 1, 2018: Journal of Molecular Graphics & Modelling
Steve J Edwards, Victoria Wakefield, Peter Cain, Charlotta Karner, Kayleigh Kew, Mariana Bacelar, Natalie Masento, Fatima Salih
BACKGROUND: Several therapies have recently been approved for use in the NHS for pretreated advanced or metastatic renal cell carcinoma (amRCC), but there is a lack of comparative evidence to guide decisions between them. OBJECTIVE: To evaluate the clinical effectiveness and cost-effectiveness of axitinib (Inlyta®, Pfizer Inc., NY, USA), cabozantinib (Cabometyx®, Ipsen, Slough, UK), everolimus (Afinitor®, Novartis, Basel, Switzerland), nivolumab (Opdivo®, Bristol-Myers Squibb, NY, USA), sunitinib (Sutent®, Pfizer, Inc...
January 2018: Health Technology Assessment: HTA
Michael Ehrhardt, Rogerio B Craveiro, Julia Velz, Martin Olschewski, Anna Casati, Stefan Schönberger, Torsten Pietsch, Dagmar Dilloo
Aberrant receptor kinase signalling and tumour neovascularization are hallmarks of medulloblastoma development and are both considered valuable therapeutic targets. In addition to VEGFR1/2, expression of PDGFR α/β in particular has been documented as characteristic of metastatic disease correlating with poor prognosis. Therefore, we have been suggested that the clinically approved multi-kinase angiogenesis inhibitor Axitinib, which specifically targets these kinases, might constitute a promising option for medulloblastoma treatment...
January 29, 2018: Journal of Cellular and Molecular Medicine
Fei Qin, Hao Yu, Chang-Rong Xu, Hui-Hui Chen, Jian-Ling Bai
We sought to investigate safety of axitinib or sorafenib in renal cell carcinoma (RCC) patients and compare toxicity of these two vascular endothelial growth factor receptor inhibitors. Databases of PubMed and Embase were searched. We included phase II and III prospective trials, as well as retrospective studies, in which patients diagnosed with RCC were treated with axitinib or sorafenib monotherapy at a starting dose of 5 mg and 400 mg twice daily, respectively. The overall incidence of high grade hypertension, fatigue, gastrointestinal toxicity and hand-foot syndrome, along with their 95% confidence intervals (CI), were calculated using fixed- or random- effects model according to heterogeneity test results...
January 18, 2018: Journal of Biomedical Research
Chongwen Xu, Guodong Xiao, Boxiang Zhang, Meng Wang, Jichang Wang, Dapeng Liu, Jing Zhang, Hong Ren, Xin Sun
Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related mortalities worldwide, yet this condition remains a poorly understood malignancy, and the subgroup of cancer stem cells (CSCs) leading to therapeutic resistance and adverse prognosis have not been well studied. CSCs frequently undergo symmetric division, which facilitates expansion of the stem cell pool, contributing to long-term relapse and therapy failure. CCAT1 could act as a miRNA sponge to influence downstream genes; however, its roles in NSCLC stem cell are unclear...
January 19, 2018: Gene Therapy
Jaume Albiol-Chiva, Josep Esteve-Romero, Juan Peris-Vicente
A method based on micellar liquid chromatography to quantify the tyrosine kinase inhibitors axitinib, lapatinib and afatinib in plasma is reported. The sample pretreatment was a simple 1/5-dilution in a pure micellar solution, filtration and direct injection, without requiring extraction or purification steps. The three drugs were resolved from the matrix in 17min, using an aqueous solution of 0.07M sodium dodecyl sulfate - 6.0% 1-pentanol, buffered at pH7 with 0.01M phosphate salt as mobile phase, running under isocratic mode at 1mL/min through a C18 column...
January 2, 2018: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
Edwin P Hui, Brigette B Y Ma, Herbert Loong, Frankie Mo, Leung Li, Ann D King, Ki Wang, Anil T Ahuja, Charles Ml Chan, Connie Wc Hui, Chi-Hang Wong, Anthony Tc Chan
PURPOSE: We hypothesized that axitinib is active with improved safety profile in nasopharyngeal carcinoma (NPC). EXPERIMENTAL DESIGN: We evaluated axitinib in preclinical models of NPC, and studied its efficacy in a phase 2 clinical trial in recurrent or metastatic NPC patients who progressed after at least one line of prior platinum-based chemotherapy. We excluded patients with local recurrence or vascular invasion. Axitinib was started at 5 mg twice-daily in continuous 4-weeks cycles...
January 4, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Shinya Takasaki, Masaki Tanaka, Masafumi Kikuchi, Masamitsu Maekawa, Yoshihide Kawasaki, Akihiro Ito, Yoichi Arai, Hiroaki Yamaguchi, Nariyasu Mano
An analytical method using high performance liquid chromatography/electrospray ionization tandem mass spectrometry has been developed and validated for simultaneous measurement of four tyrosine kinase inhibitors used for renal cell carcinoma and their metabolites in human plasma. Despite their similar structures, it is difficult to measure plasma levels of these compounds simultaneously using optimal MS parameters for each compound because a quantitative range exceeding 50,000-fold is required. To overcome this problem, we used a linear range shift technique using in-source collision-induced dissociation...
December 28, 2017: Biomedical Chromatography: BMC
Fei Qin, Hao Yu, Jianling Bai
We sought to investigate safety of axitinib or sorafenib in renal cell carcinoma (RCC) patients receiving and compare toxicity of these two vascular endothelial growth factor receptor inhibitors. Databases of PubMed and Embase were searched. Studies enrolled were phase II and III prospective trials, as well as retrospective studies, in which patients diagnosed with RCC were treated with axitinib or sorafenib monotherapy at a starting dose of 5 mg and 400 mg twice daily, respectively. The overall incidence of high grade hypertension, fatigue, gastrointestinal toxicity and hand-foot syndrome, along with their 95% confidence intervals (CI), were calculated using fixed or random effects model according to heterogeneity test results...
November 1, 2017: Journal of Biomedical Research
M Molina-Vega, J García-Alemán, A Sebastián-Ochoa, I Mancha-Doblas, J M Trigo-Pérez, F Tinahones-Madueño
PURPOSE: The aim of this study is to describe our clinical experience with tyrosine kinase inhibitors (TKIs) and to evaluate their efficacy and tolerability in patients with iodine-refractory differentiated thyroid cancer (DTC). METHODS: There were 17 patients (47.1% women, mean age: 65.7) with DTC iodine-refractory (9 papillary, 2 follicular and 3 Hürthle cell), treated with TKIs: 16 with sorafenib and 1 with lenvatinib as first-line treatment; 7 required second-line treatment (4 lenvatinib and 3 axitinib)...
December 23, 2017: Endocrine
Reinhardt Krcek, Pauline Latzer, Irenäus Anton Adamietz, Helmut Bühler, Carsten Theiss
Glioblastoma multiforme (GBM) is a highly aggressive glial brain tumor with an unfavorable prognosis despite all current therapies including surgery, radiation and chemotherapy. One characteristic of this tumor is a strong synthesis of vascular endothelial growth factor (VEGF), an angiogenesis factor, followed by pronounced vascularization. VEGF became a target in the treatment of GBM, for example with bevacizumab or the tyrosine kinase inhibitor axitinib, which blocks VEGF receptors. To improve patients' prognosis, new targets in the treatment of GBM are under investigations...
November 2017: Neural Regeneration Research
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