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Vandetanib

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https://www.readbyqxmd.com/read/28345929/utility-of-cyp3a4-and-pxr-car-cyp3a4-3a7-transgenic-mouse-models-to-assess-the-magnitude-of-cyp3a4-mediated-drug-drug-interactions
#1
Justin Q Ly, Kirsten Messick, Ann Qin, Ryan H Takahashi, Edna F Choo
Species differences in the expression, activity, regulation and substrate specificity of metabolizing enzymes preclude the use of animal models to predict clinical drug-drug interactions (DDI). The objective of this work is to determine if the transgenic (Tg) Cyp3a-/-Tg-3A4Hep/Int and Nr1i2/Nr1i3-/--Cyp3a-/-Tg-PXR-CAR-3A4/3A7Hep/Int (PXR-CAR-CYP3A4/3A7) mouse models could be used to predict in vivo DDI of 10 drugs; alprazolam, bosutinib, crizotinib, dasatinib, gefitinib, ibrutinib, regorafenib, sorafenib, triazolam, and vandetinib (as victims), with varying magnitudes of reported CYP3A4 clinical DDI...
March 27, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28318881/targeted-therapy-in-thyroid-cancer-state-of-the-art
#2
L Valerio, L Pieruzzi, C Giani, L Agate, V Bottici, L Lorusso, V Cappagli, L Puleo, A Matrone, D Viola, C Romei, R Ciampi, E Molinaro, R Elisei
Thyroid cancer typically has a good outcome following standard treatments, which include surgery, radioactive iodine ablation for differentiated tumours and treatment with thyrotropine hormone-suppressive levothyroxine. Thyroid cancers that persist or recur following these therapies have a poorer prognosis. Cytotoxic chemotherapy or external beam radiotherapy has a low efficacy in these patients. 'Target therapy' with tyrosine kinase inhibitors (TKIs) represent an important therapeutic option for the treatment of advanced cases of radioiodine refractory (RAI-R) differentiated thyroid cancer (DTC), medullary thyroid cancer (MTC) and possibly for cases of poorly differentiated (PDTC) and anaplastic thyroid cancer (ATC)...
March 16, 2017: Clinical Oncology: a Journal of the Royal College of Radiologists
https://www.readbyqxmd.com/read/28259610/vandetanib-plus-gemcitabine-versus-placebo-plus-gemcitabine-in-locally-advanced-or-metastatic-pancreatic-carcinoma-vip-a-prospective-randomised-double-blind-multicentre-phase-2-trial
#3
Gary Middleton, Daniel H Palmer, William Greenhalf, Paula Ghaneh, Richard Jackson, Trevor Cox, Anthony Evans, Victoria E Shaw, Jonathan Wadsley, Juan W Valle, David Propper, Harpreet Wasan, Stephen Falk, David Cunningham, Fareeda Coxon, Paul Ross, Srinivasan Madhusudan, Nick Wadd, Pippa Corrie, Tamas Hickish, Eithne Costello, Fiona Campbell, Charlotte Rawcliffe, John P Neoptolemos
BACKGROUND: Erlotinib is an EGFR tyrosine kinase inhibitor that has shown a significant but only marginally improved median overall survival when combined with gemcitabine in patients with locally advanced and metastatic pancreatic cancer. Vandetanib is a novel tyrosine kinase inhibitor of VEGFR2, RET, and EGFR, all of which are in involved in the pathogenesis of pancreatic cancer. We investigated the clinical efficacy of vandetanib when used in combination with gemcitabine in patients with advanced pancreatic cancer...
March 1, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28259301/effectiveness-of-antiangiogenic-drugs-in-glioblastoma-patients-a-systematic-review-and-meta-analysis-of-randomized-clinical-trials
#4
REVIEW
Giuseppe Lombardi, Ardi Pambuku, Luisa Bellu, Miriam Farina, Alessandro Della Puppa, Luca Denaro, Vittorina Zagonel
BACKGROUND: glioblastomas are highly vascularized tumors and various antiangiogenic drugs have been investigated in clinical trials showing unclear results. We performed a systematic review and a meta-analysis to clarify and evaluate their effectiveness in glioblastoma patients. PATIENTS AND METHODS: we searched relevant published and unpublished randomized clinical trials analyzing antiangiogenic drugs versus chemotherapy in glioblastoma patients from January 2006 to January 2016 in MEDLINE, WEB of SCIENCE, ASCO, ESMO and SNO databases...
March 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28209747/pediatric-adolescent-and-young-adult-thyroid-carcinoma-harbors-frequent-and-diverse-targetable-genomic-alterations-including-kinase-fusions
#5
Pierre Vanden Borre, Alexa B Schrock, Peter M Anderson, John C Morris, Andreas M Heilmann, Oliver Holmes, Kai Wang, Adrienne Johnson, Steven G Waguespack, Sai-Hong Ignatius Ou, Saad Khan, Kar-Ming Fung, Philip J Stephens, Rachel L Erlich, Vincent A Miller, Jeffrey S Ross, Siraj M Ali
BACKGROUND: Thyroid carcinoma, which is rare in pediatric patients (age 0-18 years) but more common in adolescent and young adult (AYA) patients (age 15-39 years), carries the potential for morbidity and mortality. METHODS: Hybrid-capture-based comprehensive genomic profiling (CGP) was performed prospectively on 512 consecutively submitted thyroid carcinomas, including 58 from pediatric and AYA (PAYA) patients, to identify genomic alterations (GAs), including base substitutions, insertions/deletions, copy number alterations, and rearrangements...
February 16, 2017: Oncologist
https://www.readbyqxmd.com/read/28159923/the-anti-neoplastic-activity-of-vandetanib-against-high-risk-medulloblastoma-variants-is-profoundly-enhanced-by-additional-pi3k-inhibition
#6
Rogerio B Craveiro, Michael Ehrhardt, Julia Velz, Martin Olschewski, Barbara Goetz, Torsten Pietsch, Dagmar Dilloo
Medulloblastoma is comprised of at least four molecular subgroups with distinct clinical outcome (WHO classification 2016). SHH-TP53-mutated as well as MYC-amplified Non-WNT/Non-SHH medulloblastoma show the worst prognosis.Here we present evidence that single application of the multi-kinase inhibitor Vandetanib displays anti-neoplastic efficacy against cell lines derived from high-risk SHH-TP53-mutated and MYC-amplified Non-WNT/Non-SHH medulloblastoma. The narrow target spectrum of Vandetanib along with a favourable toxicity profile renders this drug ideal for multimodal treatment approaches...
January 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/28132823/preparation-and-characterisation-of-vandetanib-eluting-radiopaque-beads-for-locoregional-treatment-of-hepatic-malignancies
#7
Alice Hagan, Gary J Phillips, Wendy M Macfarlane, Andrew W Lloyd, Peter Czuczman, Andrew L Lewis
Since their introduction around a decade ago, embolic drug-eluting beads (DEBs) have become a well-established treatment option for the locoregional transarterial treatment of hepatic malignancies. Despite this success, the therapy is seen to be limited by the choice of drug and more effective options are therefore being sought. These include the small molecule multi-tyrosine kinase inhibitors (MTKi), which exert an anti-angiogenic and anti-proliferative effect that could be highly beneficial in combating some of the unwanted downstream consequences of embolization...
April 1, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28098949/identification-of-cellular-targets-involved-in-cardiac-failure-caused-by-pki-in-oncology-an-approach-combining-pharmacovigilance-and-pharmacodynamics
#8
Emilie Patras de Campaigno, Emmanuelle Bondon-Guitton, Guy Laurent, Francois Montastruc, Jean-Louis Montastruc, Maryse Lapeyre-Mestre, Fabien Despas
AIMS: The aims of the present study were to evaluate the risk of cardiac failure (CF) associated with 15 anticancer protein kinase inhibitors (PKIs) through a case/noncase analysis and to identify which PK(s) and pathways are involved in PKI-induced CF. METHODS: In order to evaluate the risk of CF, adjusted reporting odds ratios (aRORs) were calculated for the 15 anticancer PKIs in the World Health Organization safety report database (VigiBase®). We realised a literature review to identify 21 protein kinases (PKs) that were possibly involved in CF caused by PKIs...
January 18, 2017: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28068878/long-term-control-of-hypercortisolism-by-vandetanib-in-a-case-of-medullary-thyroid-carcinoma-with-a-somatic-ret-mutation
#9
Anne-Cécile Paepegaey, Béatrix Cochand-Priollet, Estelle Louiset, Pierre-Olivier Sarfati, Marco Alifano, Nelly Burnichon, Marie Bienvenu-Perrard, Najiba Lahlou, Léopoldine Bricaire, Lionel Groussin
BACKGROUND: Medullary thyroid carcinomas (MTCs) complicated by ectopic Cushing's syndrome (CS) have a poor prognosis, partially due to the difficulty in controlling hypercortisolism by adrenal blocking drugs. Recent reports (including the initial follow-up of this patient) have suggested that tyrosine kinase inhibitors (TKIs) may be a therapeutic option due to an anti-secretory action on ACTH. However, there is a lack of long-term follow-up studies. PATIENT FINDINGS: The case is reported of a 58-year-old man with MTC-related CS resistant to a combination of several anti-cortisolic drugs...
March 13, 2017: Thyroid: Official Journal of the American Thyroid Association
https://www.readbyqxmd.com/read/28052652/anti-angiogenic-therapy-in-patients-with-advanced-gastric-and-gastroesophageal-junction-cancer-a-systematic-review
#10
Li-Tzong Chen, Do-Youn Oh, Min-Hee Ryu, Kun-Huei Yeh, Winnie Yeo, Roberto Carlesi, Rebecca Cheng, Jongseok Kim, Mauro Orlando, Yoon-Koo Kang
Despite advancements in therapy for advanced gastric and gastroesophageal junction cancers, their prognosis remains dismal. Tumor angiogenesis plays a key role in cancer growth and metastasis, and recent studies indicate that pharmacologic blockade of angiogenesis is a promising approach to therapy. In this systematic review, we summarize current literature on the clinical benefit of anti-angiogenic agents in advanced gastric cancer. We conducted a systematic search of PubMed and conference proceedings including the American Society of Clinical Oncology, the European Society for Medical Oncology, and the European Cancer Congress...
January 3, 2017: Cancer Research and Treatment: Official Journal of Korean Cancer Association
https://www.readbyqxmd.com/read/27986807/effects-of-4-multitargeted-receptor-tyrosine-kinase-inhibitors-on-regional-hemodynamics-in-conscious-freely-moving-rats
#11
Joanne J Carter, Laurice V Fretwell, Jeanette Woolard
VEGF inhibitors, including receptor tyrosine kinase inhibitors, are used as adjunct therapies in a number of cancer treatments. An emerging issue with these drugs is that most cause hypertension. To gain insight into the physiological mechanisms involved, we evaluated their regional hemodynamic effects in conscious rats. Male Sprague Dawley rats (350-450 g) were chronically implanted with pulsed Doppler flow probes (renal and mesenteric arteries, and the descending abdominal aorta) and catheters (jugular vein, peritoneal cavity, and distal abdominal aorta)...
March 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/27983649/design-and-synthesis-of-vandetanib-derivatives-containing-nitroimidazole-groups-as-tyrosine-kinase-inhibitors-in-normoxia-and-hypoxia
#12
Huiqiang Wei, Deguan Li, Xiangbo Yang, Haihua Shang, Saijun Fan, Yiliang Li, Dan Song
Sixteen novel epidermal growth factor receptor (EGFR)/vascular endothelial growth factor (VEGF)-2 inhibitors (nitroimidazole-substituted 4-anilinoquinazoline derivatives (16a-p)) were designed and prepared via the introduction of a nitroimidazole group in the piperidine side chain and modification on the aniline moiety of vandetanib. Preliminary biological tests showed that comparing with vandetanib, some target compounds exhibited excellent EGFR inhibitory activities and anti-proliferative over A549/H446 cells in hypoxia...
December 14, 2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/27940520/exploring-the-benefit-risk-associated-with-antiangiogenic-agents-for-the-treatment-of-non-small-cell-lung-cancer-patients
#13
REVIEW
Razelle Kurzrock, David J Stewart
Following the approval of bevacizumab, an antibody targeting VEGF-A, for advanced non-squamous non-small cell lung cancer (NSCLC) in 2006, intensive efforts were put into the clinical development of antiangiogenic agents for NSCLC. Currently, the other antiangiogenic agents approved for NSCLC are ramucirumab, a VEGF receptor-2 (VEGFR-2)-targeting antibody indicated for both squamous and non-squamous NSCLC in the United States, and nintedanib, an anti-VEGFR-1/2/3, platelet-derived growth factor receptor-α/β, fibroblast growth factor receptor-1/2/3 angiokinase inhibitor indicated for adenocarcinoma of the lung in the European Union...
December 9, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27873490/egf-induced-ret-inhibitor-resistance-in-ccdc6-ret-lung-cancer-cells
#14
Hyun Chang, Ji Hea Sung, Sung Ung Moon, Han Soo Kim, Jin Won Kim, Jong Seok Lee
PURPOSE: Rearrangement of the proto-oncogene rearranged during transfection (RET) has been newly identified potential driver mutation in lung adenocarcinoma. Clinically available tyrosine kinase inhibitors (TKIs) target RET kinase activity, which suggests that patients with RET fusion genes may be treatable with a kinase inhibitor. Nevertheless, the mechanisms of resistance to these agents remain largely unknown. Thus, the present study aimed to determine whether epidermal growth factor (EGF) and hepatocyte growth factor (HGF) trigger RET inhibitor resistance in LC-2/ad cells with CCDC6-RET fusion genes...
January 2017: Yonsei Medical Journal
https://www.readbyqxmd.com/read/27855236/vandetanib-induces-a-marked-anti-tumor-effect-and-amelioration-of-ectopic-cushing-s-syndrome-in-a-medullary-thyroid-carcinoma-patient
#15
Hashem Bseiso, Naama Lev-Cohain, David J Gross, Simona Grozinsky-Glasberg
A 55-year-old woman diagnosed with sporadic MTC underwent total thyroidectomy 20 years ago. After the first surgery, elevated calcitonin levels in parallel with local disease persistence were noted and therefore she underwent repeated neck dissections. During follow-up, multiple foci of metastatic disease were noted in the neck and mediastinal lymph nodes, lungs and bones; however, the disease had an indolent course for a number of years, in parallel with a calcitonin doubling time of more than two years and without significant symptoms...
2016: Endocrinology, Diabetes & Metabolism Case Reports
https://www.readbyqxmd.com/read/27843809/effect-of-an-outreach-programme-on-vandetanib-safety-in-medullary-thyroid-cancer
#16
Lars Bastholt, Michael C Kreissl, Dagmar Führer, Ana L Maia, Laura D Locati, Léa Maciel, Yi Wu, Kevin N Heller, Alan Webster, Rossella Elisei
OBJECTIVES: Effective management of adverse events (AEs) following vandetanib treatment is important to maximize clinical benefits. We examined whether more frequent contact with vandetanib-treated patients reduced AEs of CTCAE grade 2 or higher. STUDY DESIGN: In this open-label, multicentre, phase III study, patients with locally advanced or metastatic medullary thyroid cancer were randomized to a patient outreach programme (outreach) or a standard AE monitoring schedule (vandetanib control) for 52 weeks...
September 2016: European Thyroid Journal
https://www.readbyqxmd.com/read/27825616/vandetanib-in-patients-with-previously-treated-ret-rearranged-advanced-non-small-cell-lung-cancer-luret-an-open-label-multicentre-phase-2-trial
#17
Kiyotaka Yoh, Takashi Seto, Miyako Satouchi, Makoto Nishio, Noboru Yamamoto, Haruyasu Murakami, Naoyuki Nogami, Shingo Matsumoto, Takashi Kohno, Koji Tsuta, Katsuya Tsuchihara, Genichiro Ishii, Shogo Nomura, Akihiro Sato, Atsushi Ohtsu, Yuichiro Ohe, Koichi Goto
BACKGROUND: RET rearrangements are rare oncogenic alterations in non-small-cell lung cancer (NSCLC). Vandetanib is a multitargeted tyrosine kinase inhibitor exhibiting RET kinase activity. We aimed to assess the efficacy and safety of vandetanib in patients with advanced RET-rearranged NSCLC. METHODS: In this open-label, multicentre, phase 2 trial (LURET), patients with advanced RET-rearranged NSCLC continuously received 300 mg of oral vandetanib daily. RET-positive patients were screened using a nationwide genomic screening network of about 200 participating institutions...
January 2017: Lancet Respiratory Medicine
https://www.readbyqxmd.com/read/27819766/safety-and-tolerability-of-vandetanib-in-japanese-patients-with-medullary-thyroid-cancer-a-phase-i-ii-open-label-study
#18
Keita Uchino, Masato Komoda, Junichi Tomomatsu, Takahiro Okamoto, Kiyomi Horiuchi, Akihito Tsuji, Yasuhiro Ito, Takuya Todo, Ki Rito, Shunji Takahashi
OBJECTIVE: In a phase III trial, Western patients with medullary thyroid cancer (MTC) treated with the oral multikinase inhibitor vandetanib showed significantly improved progression-free survival (PFS) and objective response rate (ORR) compared with placebo. The biology of MTC and pharmacokinetics (PK) are similar for Japanese and Western patients; therefore, similar clinical benefit is anticipated in the Japanese population. This study evaluated the safety and tolerability of vandetanib in Japanese patients with unresectable locally advanced or metastatic MTC...
February 2017: Endocrine Practice
https://www.readbyqxmd.com/read/27803005/vandetanib-in-pretreated-patients-with-advanced-non-small-cell-lung-cancer-harboring-ret-rearrangement-a-phase-ii-clinical-trial
#19
S-H Lee, J-K Lee, M-J Ahn, D-W Kim, J-M Sun, B Keam, T M Kim, D S Heo, J S Ahn, Y-L Choi, H-S Min, Y K Jeon, K Park
BACKGROUND: Chromosomal rearrangements involving RET, which are found in about 1% of non-small cell lung cancer (NSCLC), define a unique molecular subset. We performed this study to examine the efficacy and safety of vandetanib 300 mg daily in this patient population. PATIENTS AND METHODS: This study was a multi-center, open-label, phase II clinical trial. Patients were enrolled if they had metastatic or recurrent NSCLC with a RET rearrangement, which was confirmed by fluorescence in situ hybridization, had progressive disease against platinum-based doublet chemotherapy, and had a performance status of 0-2...
November 1, 2016: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/27799362/animal-models-of-medullary-thyroid-cancer-state-of-the-art-and-view-to-the-future
#20
Giovanni Vitale, Germano Gaudenzi, Luisa Circelli, Marco Federico Manzoni, Andrea Bassi, Niccolò Fioritti, Antongiulio Faggiano, Annamaria Al Colao
Medullary thyroid carcinoma is a neuroendocrine tumour originating from parafollicular C cells accounting for 5-10% of thyroid cancers. Increased understanding of disease-specific molecular targets of therapy has led to the regulatory approval of two drugs (vandetanib and cabozantinib) for the treatment of medullary thyroid carcinoma. These drugs increase progression free survival, however, they are often poorly tolerated and most treatment responses are transient. Animal models are indispensable tools for investigating the pathogenesis, mechanisms for tumour invasion and metastasis, and new therapeutic approaches for cancer...
October 31, 2016: Endocrine-related Cancer
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