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https://www.readbyqxmd.com/read/29331859/development-of-a-method-to-determine-axitinib-lapatinib-and-afatinib-in-plasma-by-micellar-liquid-chromatography-and-validation-by-the-european-medicines-agency-guidelines
#1
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
https://www.readbyqxmd.com/read/29301831/efficacy-safety-and-pharmacokinetics-of-axitinib-in-nasopharyngeal-carcinoma-a-preclinical-and-phase-2-correlative-study
#2
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
https://www.readbyqxmd.com/read/29283445/simultaneous-analysis-of-oral-anticancer-drugs-for-renal-cell-carcinoma-in-human-plasma-using-liquid-chromatography-electrospray-ionization-tandem-mass-spectrometry
#3
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
https://www.readbyqxmd.com/read/29277834/safety-and-toxicity-of-axitinib-and-sorafenib-monotherapy-for-patients-with-renal-cell-carcinoma-a-meta-analysis
#4
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
https://www.readbyqxmd.com/read/29275532/tyrosine-kinase-inhibitors-in-iodine-refractory-differentiated-thyroid-cancer-experience-in-clinical-practice
#5
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
https://www.readbyqxmd.com/read/29239327/influence-of-vascular-endothelial-growth-factor-and-radiation-on-gap-junctional-intercellular-communication-in-glioblastoma-multiforme-cell-lines
#6
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
https://www.readbyqxmd.com/read/29239194/-immunotherapy-of-renal-cell-carcinoma
#7
A Poprach, R Lakomý, T Büchler
Treatment of renal cell carcinoma is still palliative. Targeted therapy increases response rates and prolongs overall survival and progression-free survival compared with cytokines and chemotherapy. Checkpoint inhibitors constitute the up-date of therapeutic approaches, and anti-PD-1 antibody, one checkpoint inhibitor, is now well established as a second and/or third palliative treatment for patients with renal cell carcinoma. In this study, we present the latest data from current studies on cytokines, cancer vaccines, ipilimumab, and nivolumab...
2017: Klinická Onkologie: Casopis Ceské a Slovenské Onkologické Spolecnosti
https://www.readbyqxmd.com/read/29238223/the-effect-of-medication-nonadherence-on-progression-free-survival-among-patients-with-renal-cell-carcinoma
#8
Jason Shafrin, Jeffrey Sullivan, Jacquelyn W Chou, Michael N Neely, Justin F Doan, J Ross Maclean
Objective: To examine how observed medication nonadherence to 2 second-line, oral anticancer medications (axitinib and everolimus) affects progression-free survival (PFS) among patients with renal cell carcinoma. Methods: We used an adherence-exposure-outcome model to simulate the impact of adherence on PFS. Using a pharmacokinetic/pharmacodynamic (PK/PD) population model, we simulated drug exposure measured by area under the plasma concentration-time curve (AUC) and minimum blood or trough concentration (Cmin) under 2 scenarios: 1) optimal adherence and 2) real-world adherence...
2017: Cancer Management and Research
https://www.readbyqxmd.com/read/29220734/high-throughput-routine-determination-of-17-tyrosine-kinase-inhibitors-by-lc-ms-ms
#9
Camille Merienne, Marine Rousset, Dominique Ducint, Nadège Castaing, Karine Titier, Mathieu Molimard, Stéphane Bouchet
Several studies have shown that therapeutic drug monitoring of tyrosine kinase inhibitors (TKI) can improve their benefit in cancer. An analytical tool has been developed in order to quantify 17 tyrosine kinase inhibitors and 2 metabolites in human plasma (afatinib, axitinib, bosutinib, crizotinib, dabrafenib, dasatinib, erlotinib, gefitinib, imatinib, lapatinib, nilotinib, ponatinib, regorafenib, regorafenib M2, regorafenib M5, ruxolitinib, sorafenib, sunitinib, vandetanib). Drugs were arranged in four groups, according to their plasma concentration range: 0...
November 28, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/29211397/efficacy-of-targeted-therapy-for-advanced-renal-cell-carcinoma-a-systematic-review-and-meta-analysis-of-randomized-controlled-trials
#10
Chao Wei, Shen Wang, Zhangqun Ye, Zhiqiang Chen
We conducted a systematic review and meta-analysis of the literature on the efficacy of the targeted therapies in the treatment of advanced RCC and, via an indirect comparison, to provide an optimal treatment among these agents. A systematic search of Medline, Scopus, Cochrane Library and Clinical Trials unpublished was performed up to Jan 1, 2015 to identify eligible randomized trials. Outcomes of interest assessing a targeted agent included progression free survival (PFS), overall survival (OS) and objective response rate (ORR)...
December 7, 2017: International Braz J Urol: Official Journal of the Brazilian Society of Urology
https://www.readbyqxmd.com/read/29198329/examining-the-bleeding-incidences-associated-with-targeted-therapies-used-in-metastatic-renal-cell-carcinoma
#11
REVIEW
MacKenzie Crist, Elizabeth Hansen, Lipika Chablani, Elizabeth Guancial
A systematic review was conducted to illustrate the bleeding risks associated with targeted therapies used in the treatment of metastatic renal cell carcinoma (mRCC). Eligible studies included phase II, III, or IV clinical trials using pazopanib, sunitinib, cabozantinib, lenvatinib, everolimus, temsirolimus, bevacizumab, axitinib, and/or sorafenib in the setting of mRCC. Types of bleeding event(s), bleeding event frequency, and incidence of thrombocytopenia were collected from the relevant articles. ClinicalTrials...
December 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/29195016/association-of-high-cost-sharing-and-targeted-therapy-initiation-among-elderly-medicare-patients-with-metastatic-renal-cell-carcinoma
#12
Pengxiang Li, Yu-Ning Wong, Jordan Jahnke, Amy R Pettit, Jalpa A Doshi
High out-of-pocket costs may limit access to oral therapies covered by patients' prescription drug benefits. We explored financial barriers to treatment initiation in patients newly diagnosed with metastatic renal cell carcinoma (mRCC) by comparing Medicare Part D patients with low out-of-pocket costs due to receipt of full low-income subsidies (LIS beneficiaries) to their counterparts who were responsible for more than 25% cost sharing during Medicare's initial coverage phase (non-LIS beneficiaries). We used 2011-2013 100% Medicare claims for non-LIS and LIS beneficiaries newly diagnosed with metastases in the liver, lung, or bone to examine targeted therapy treatment initiation rates and time to initiation for (1) oral medications (sorafenib, sunitinib, everolimus, pazopanib, or axitinib) covered under Medicare's prescription drug benefit (Part D); (2) injected or infused medications (temsirolimus or bevacizumab) covered by Medicare's medical benefit (Part B); and (3) any (Part D or Part B) targeted therapy...
December 1, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/29182025/vegf-mediated-tight-junctions-pathological-fenestration-enhances-doxorubicin-loaded-glycolipid-like-nanoparticles-traversing-bbb-for-glioblastoma-targeting-therapy
#13
Lijuan Wen, Yanan Tan, Suhuan Dai, Yun Zhu, Tingting Meng, Xiqin Yang, Yupeng Liu, Xuan Liu, Hong Yuan, Fuqiang Hu
The existence of blood-brain barrier (BBB) greatly hindered the penetration and accumulation of chemotherapeutics into glioblastoma (GBM), accompany with poor therapeutic effects. The growth of GBM supervene the impairment of tight junctions (TJs); however, the pathogenesis of BBB breakdown in GBM is essentially poorly understood. This study found that vascular endothelial growth factor (VEGF) secreted by GBM cells plays an important role in increasing the permeability of BBB by disrupting endothelial tight junction proteins claudin-5 and thus gave doxorubicin (DOX)-loaded glycolipid-like nanoparticles (Ap-CSSA/DOX), an effective entrance to brain tumor region for GBM-targeting therapy...
November 2017: Drug Delivery
https://www.readbyqxmd.com/read/29165815/development-and-validation-of-a-liquid-chromatography-tandem-mass-spectrometry-analytical-method-for-the-therapeutic-drug-monitoring-of-eight-novel-anticancer-drugs
#14
M Herbrink, N de Vries, H Rosing, A D R Huitema, B Nuijen, J H M Schellens, J H Beijnen
To support therapeutic drug monitoring (TDM) of patients with cancer, a fast and accurate method for simultaneous quantification of the registered anticancer drugs afatinib, axitinib, ceritinib, crizotinib, dabrafenib, enzalutamide, regorafenib and trametinib in human plasma using liquid chromatography tandem mass spectrometry was developed and validated. Human plasma samples were collected from treated patients and stored at -20 (o) C. Analytes and internal standards (stable isotopically labeled analytes) were extracted with acetonitrile...
November 22, 2017: Biomedical Chromatography: BMC
https://www.readbyqxmd.com/read/29128510/enzymes-involved-in-tumor-driven-angiogenesis-a-valuable-target-for-anticancer-therapy
#15
REVIEW
Biagio Ricciuti, Jennifer Foglietta, Vanessa Bianconi, Amirhossein Sahebkar, Matteo Pirro
Angiogenesis plays a pivotal role in cancer progression and is required for tissue invasion and metastasis. Starting with Folkman's initial observations in 1971, basic research continued to shed new molecular insight into this multifaceted process, leading to the development of several anti-angiogenic drugs. To date, anti-vascular endothelial growth factor monoclonal antibodies, such as bevacizumab and ramucirumab, and receptor tyrosine kinase inhibitors (e.g., sorafenib, sunitinib, regorafenib and axitinib) have had a profound impact on the way we treat patients with advanced cancer, providing in some cases unprecedented clinical benefit...
November 8, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/29109792/mir-205-yap1-in-activated-fibroblasts-of-breast-tumor-promotes-vegf-independent-angiogenesis-through-stat3-signaling
#16
Yan-E Du, Gang Tu, Guanglun Yang, Genyou Li, Dan Yang, Lei Lang, Lei Xi, Kexin Sun, Yanlin Chen, Kunxian Shu, Huadong Liao, Manran Liu, Yixuan Hou
Tumor microenvironment contributes to tumor angiogenesis. However, the role of the activated cancer associated-fibroblasts (CAFs) in angiogenesis is still unclear. Here we report that miR-205/YAP1 signaling in the activated stromal fibroblasts plays a critical role in VEGF-independent angiogenesis in breast tumor. Methods: miR-205 expression was assessed by quantitative real-time polymerase chain reaction (qRT-PCR); YAP1 expression by qRT-PCR, western blotting and immunohistochemistry; IL11 and IL15 expression by qRT-PCR, western blotting and ELISA...
2017: Theranostics
https://www.readbyqxmd.com/read/29079346/axitinib-attenuates-intraplaque-angiogenesis-haemorrhages-and-plaque-destabilization-in-mice
#17
Bieke Van der Veken, Guido R Y De Meyer, Wim Martinet
AIM: An increased density of intraplaque (IP) microvessels in ruptured versus nonruptured human plaques suggests that IP neovascularization has a major causative effect on plaque development and instability. Possibly, vascular endothelial growth factor (VEGF) or other angiogenic factors mediate IP microvessel growth and plaque destabilization. Because apolipoprotein deficient mice with a heterozygous mutation (C1039G+/-) in the fibrillin-1 gene (ApoE-/-Fbn1C1039G+/-) manifest substantial IP neovascularization, they represent a unique tool to further investigate angiogenesis and its role in atherosclerosis...
October 31, 2017: Vascular Pharmacology
https://www.readbyqxmd.com/read/29046793/updated-recommendation-on-molecular-targeted-therapy-for-metastatic-renal-cell-cancer
#18
Senji Hoshi, Kenji Numahata, Hidenori Kanno, Masahiko Sato, Akihito Kuromoto, Kunihisa Nezu, Takanari Sakai, Chihito Konno, Yuichi Ishizuka, Hideaki Izumi, Katsuyuki Taguchi, Kunio Ono, Kiyotsugu Hoshi, Satoshi Kanto, Rika Takahashi, Bilim Vladimir, Naoe Akimoto, Isoji Sasagawa, Shoichiro Ohta
Molecular-targeted therapy was recommended for the systemic therapy of renal cell cancer (RCC) in the RCC guidelines, but these guidelines do not address the order of administration of the multiple presently available agents. There are several aspects that remain unknown regarding the optimal administration order and combination of molecular-targeted drugs. Until the optimal treatment sequence is determined by clinical trials, treatment individualization is required for each patient based on patient and disease characteristics...
October 2017: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/29033542/axitinib-in-the-treatment-of-renal-cell-carcinoma-design-development-and-place-in-therapy
#19
REVIEW
Audrey Bellesoeur, Edith Carton, Jerome Alexandre, Francois Goldwasser, Olivier Huillard
Since 2005, the approved first-line treatment of metastatic renal cell carcinoma consists in tyrosine kinase inhibitors (TKIs) targeting the vascular endothelial growth factor receptors (VEGFRs). Axitinib is an oral second-generation TKI and a potent VEGFR inhibitor with a half maximal inhibitory concentration for the VEGF family receptors 10-fold lower than other TKIs. Axitinib activity in renal cell carcinoma (RCC) patients has been studied in various settings and particularly as second-line treatment. In this setting, axitinib with clinically based dose escalation compared to sorafenib has demonstrated an improvement in progression-free survival in a randomized Phase III trial leading to US Food and Drug Administration approval...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28988341/randomized-phase-ii-trial-comparing-axitinib-with-the-combination-of-axitinib-and-lomustine-in-patients-with-recurrent-glioblastoma
#20
J Duerinck, S Du Four, F Bouttens, C Andre, V Verschaeve, F Van Fraeyenhove, C Chaskis, N D'Haene, M Le Mercier, A Rogiers, A Michotte, I Salmon, B Neyns
Axitinib is a small molecule tyrosine kinase inhibitor with high affinity and specificity for the family of vascular endothelial growth factor receptors. It has previously demonstrated anti-tumor activity in a small cohort of patients with recurrent glioblastoma (rGB). We conducted a non-comparative randomized phase II clinical trial investigating axitinib monotherapy versus axitinib plus lomustine (LOM) in patients with rGB. Primary endpoint was 6 month progression-free survival (6mPFS). Patients who progressed on axitinib-monotherapy were allowed to cross-over...
October 7, 2017: Journal of Neuro-oncology
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