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Crizotinib

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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
#1
E Patras de Campaigno, E Bondon-Guitton, G Laurent, F Montastruc, J L Montastruc, M Lapeyre-Mestre, F Despas
AIMS: To evaluate the risk of cardiac failure (CF) of 15 anticancer protein kinase inhibitors (PKIs) through a case/non-case analysis and to identify which PK(s) and pathways are involved in PKI-induced CF. METHODS: To evaluate the risk of CF, adjusted reporting odds ratios (aRORs) were calculated for the 15 anticancer PKIs in the WHO safety report database (VigiBase®). We realised a literature review to identify 21 PK possibly involved in CF caused by PKIs. Pearson's correlation coefficients (r) between aROR and affinity data of the 15 PKIs for the 21 PKs were calculated to identify the cellular target most likely involved in PKI-induced CF...
January 18, 2017: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28081478/pulmonary-sarcomatoid-carcinoma-with-alk-rearrangement-frequency-clinical-pathologic-characteristics-and-response-to-alk-inhibitor
#2
Xinru Chen, Yu Zhang, Jiabin Lu, Chunwei Xu, Jianzhong Liang, Fang Wang, Wenyong Sun, Sangao Fang, Jingping Yuan, Huijuan Wang, Hui Wang, Xuewen Liu, Likun Chen
PURPOSE: The incidence of anaplastic lymphoma kinase (ALK) rearrangement in pulmonary sarcomatoid carcinoma (PSC) is controversial. In this study, we aimed to reveal the reliable frequency and the clinical-pathologic characteristics of pulmonary sarcomatoid carcinoma (PSC) with ALK rearrangement in Chinese population, and to provide insight into the translatability of anti-ALK treatment in this treatment-refractory disease. METHODS: Immunohistochemistry (IHC) using a Ventana anti-ALK (D5F3) rabbit monoclonal antibody was performed in 141 PSC specimens collected from multiple medical centers...
January 9, 2017: Translational Oncology
https://www.readbyqxmd.com/read/28077299/anaplastic-lymphoma-kinase-alk-inhibitors-in-the-treatment-of-alk-driven-lung-cancers
#3
REVIEW
Robert Roskoski
Anaplastic lymphoma kinase is expressed in two-thirds of the anaplastic large-cell lymphomas as an NPM-ALK fusion protein. Physiological ALK is a receptor protein-tyrosine kinase within the insulin receptor superfamily of proteins that participates in nervous system development. The EML4-ALK fusion protein and four other ALK-fusion proteins play a fundamental role in the development in about 5% of non-small cell lung cancers. The amino-terminal portions of the ALK fusion proteins result in dimerization and subsequent activation of the ALK protein kinase domain that plays a key role in the pathogenesis of various tumors...
January 8, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28075018/c-met-as-a-potential-target-for-the-treatment-of-gastrointestinal-cancer-current-status-and-future-perspectives
#4
REVIEW
Afsaneh Bahrami, Soodabeh Shahidsales, Majid Khazaei, Majid Ghayour-Mobarhan, Mina Maftouh, Seyed Mahdi Hassanian, Amir Avan
Aberrant activation of the HGF/c-Met signalling pathways is shown to be related with cell proliferation, progression, metastasis and worse prognosis in several tumor types, including gastrointestinal cancers, suggesting its value as a stimulating-target for cancer-therapy. Several approaches have been developed for targeting HGF and/or c-Met, and one of them, crizotinib (dual c-Met/ALK inhibitor), is recently been approved by FDA for lung-cancers with ALK-rearrangement. The main aim of current review is to give an overview on the role of c-Met/HGF pathway in gastrointestinal cancer, in preclinical and clinical trials...
January 11, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28066567/sequencing-alk-inhibitors-alectinib-in-crizotinib-resistant-patients-a-phase-2-trial-by-shaw-et-al
#5
EDITORIAL
Laura Mezquita, Benjamin Besse
No abstract text is available yet for this article.
November 2016: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/28065466/sequential-use-of-anaplastic-lymphoma-kinase-inhibitors-in-japanese-patients-with-alk-rearranged-non-small-cell-lung-cancer-a%C3%A2-retrospective-analysis
#6
Tetsuhiko Asao, Yutaka Fujiwara, Kota Itahashi, Shinsuke Kitahara, Yasushi Goto, Hidehito Horinouchi, Shintaro Kanda, Hiroshi Nokihara, Noboru Yamamoto, Kazuhisa Takahashi, Yuichiro Ohe
BACKGROUND: Second-generation anaplastic lymphoma kinase (ALK) inhibitors, such as alectinib and ceritinib, have recently been approved for treatment of ALK-rearranged non-small-cell lung cancer (NSCLC). An optimal strategy for using 2 or more ALK inhibitors has not been established. We sought to investigate the clinical impact of sequential use of ALK inhibitors on these tumors in clinical practice. PATIENTS AND METHODS: Patients with ALK-rearranged NSCLC treated from May 2010 to January 2016 at the National Cancer Center Hospital were identified, and their outcomes were evaluated retrospectively...
December 7, 2016: Clinical Lung Cancer
https://www.readbyqxmd.com/read/28056412/toxicity-of-concurrent-stereotactic-radiotherapy-and-targeted-therapy-or-immunotherapy-a-systematic-review
#7
REVIEW
Stephanie G C Kroeze, Corinna Fritz, Morten Hoyer, Simon S Lo, Umberto Ricardi, Arjun Sahgal, Rolf Stahel, Roger Stupp, Matthias Guckenberger
BACKGROUND AND PURPOSE: Both stereotactic radiotherapy (SRT) and immune- or targeted therapy play an increasingly important role in personalized treatment of metastatic disease. Concurrent application of both therapies is rapidly expanding in daily clinical practice. In this systematic review we summarize severe toxicity observed after concurrent treatment. MATERIAL AND METHODS: PubMed and EMBASE databases were searched for English literature published up to April 2016 using keywords "radiosurgery", "local ablative therapy", "gamma knife" and "stereotactic", combined with "bevacizumab", "cetuximab", "crizotinib", "erlotinib", "gefitinib", "ipilimumab", "lapatinib", "sorafenib", "sunitinib", "trastuzumab", "vemurafenib", "PLX4032", "panitumumab", "nivolumab", "pembrolizumab", "alectinib", "ceritinib", "dabrafenib", "trametinib", "BRAF", "TKI", "MEK", "PD1", "EGFR", "CTLA-4" or "ALK"...
December 19, 2016: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28054318/treating-patients-with-alk-rearranged-non-small-cell-lung-cancer-mechanisms-of-resistance-and-strategies-to-overcome-it
#8
REVIEW
M Drizou, E A Kotteas, N Syrigos
Anaplastic lymphoma kinase (ALK) rearrangement is detected in 3-7% of patients with non-small-cell lung cancer. Crizotinib is an ALK inhibitor, which was approved in 2011 for the treatment of ALK-positive lung cancer. Despite the initial enthusiasm, most of the patients develop resistance within the first year of treatment. The main mechanisms are secondary mutations and bypass track activation. Moreover, crizotinib has low penetration into the central nervous system. The need to overcome these limitations has led to the development of second-generation inhibitors that have better effectiveness against crizotinib-resistant mutations and brain metastases...
January 4, 2017: Clinical & Translational Oncology
https://www.readbyqxmd.com/read/28050598/alk-a-tyrosine-kinase-target-for-cancer-therapy
#9
REVIEW
Vijaykumar R Holla, Yasir Y Elamin, Ann Marie Bailey, Amber M Johnson, Beate C Litzenburger, Yekaterina B Khotskaya, Nora S Sanchez, Jia Zeng, Md Abu Shufean, Kenna R Shaw, John Mendelsohn, Gordon B Mills, Funda Meric-Bernstam, George R Simon
The anaplastic lymphoma kinase (ALK) gene plays an important physiologic role in the development of the brain and can be oncogenically altered in several malignancies, including non-small-cell lung cancer (NSCLC) and anaplastic large cell lymphomas (ALCL). Most prevalent ALK alterations are chromosomal rearrangements resulting in fusion genes, as seen in ALCL and NSCLC. In other tumors, ALK copy-number gains and activating ALK mutations have been described. Dramatic and often prolonged responses are seen in patients with ALK alterations when treated with ALK inhibitors...
January 2017: Cold Spring Harbor Molecular Case Studies
https://www.readbyqxmd.com/read/28050149/treatment-patterns-and-survival-in-patients-with-alk-positive-non-small-cell-lung-cancer-a-canadian-retrospective-study
#10
S Kayaniyil, M Hurry, J Wilson, P Wheatley-Price, B Melosky, J Rothenstein, V Cohen, C Koch, J Zhang, K Osenenko, G Liu
BACKGROUND: Crizotinib was the first agent approved for the treatment of anaplastic lymphoma kinase (ALK)-positive (+) non-small-cell lung cancer (nsclc), followed by ceritinib. However, patients eventually progress or develop resistance to crizotinib. With limited real-world data available, the objective of the present work was to evaluate treatment patterns and survival after crizotinib in patients with locally advanced or metastatic ALK+ nsclc in Canada. METHODS: In this retrospective study at 6 oncology centres across Canada, medical records of patients with locally advanced or metastatic ALK+ nsclc were reviewed...
December 2016: Current Oncology
https://www.readbyqxmd.com/read/28039177/differential-protein-stability-and-clinical-responses-of-eml4-alkfusion-variants-to-various-alk-inhibitors-in-advanced-alk-rearranged-non-small-cell-lung-cancer
#11
C G Woo, S Seo, S W Kim, S J Jang, K S Park, J Y Song, B Lee, M W Richards, R Bayliss, D H Lee, J Choi
BACKGROUND: Anaplastic lymphoma kinase (ALK) inhibition using crizotinib has become the standard of care in advanced ALK-rearranged non-small cell lung cancer (NSCLC), but the treatment outcomes and duration of response vary widely. Echinoderm microtubule-associated protein-like 4 (EML4)-ALK is the most common translocation, and the fusion variants show different sensitivity to crizotinib in vitro. However, there are only limited data on the specific EML4-ALK variants and clinical responses of patients to various ALK inhibitors...
December 29, 2016: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28035616/effects-of-renal-function-on-crizotinib-pharmacokinetics-dose-recommendations-for-patients-with-alk-positive-non-small-cell-lung-cancer
#12
Weiwei Tan, Shinji Yamazaki, Theodore R Johnson, Rong Wang, Melissa T O'Gorman, Leonid Kirkovsky, Tanya Boutros, Nicoletta M Brega, Akintunde Bello
BACKGROUND AND OBJECTIVES: Crizotinib (250 mg twice daily) is the first anaplastic lymphoma kinase (ALK) inhibitor approved for treatment of ALK-positive non-small-cell lung cancer (NSCLC). The objectives of the current study were to evaluate the effects of mild, moderate, and severe renal impairment on crizotinib pharmacokinetics and to make crizotinib dosing recommendations for ALK-positive NSCLC patients with renal impairment on the basis of the findings. METHODS: The effects of varying degrees of renal impairment on crizotinib pharmacokinetics were evaluated by: (1) analysis of mild and moderate renal impairment on multiple-dose pharmacokinetics of crizotinib in ALK-positive NSCLC patients from the PROFILE 1001 and PROFILE 1005 trials; (2) analysis of severe renal impairment on single-dose pharmacokinetics of crizotinib in volunteers (Study 1020); and (3) prediction of the effect of severe renal impairment on multiple-dose crizotinib pharmacokinetics using a physiologically-based pharmacokinetic model of crizotinib...
December 29, 2016: Clinical Drug Investigation
https://www.readbyqxmd.com/read/28032129/first-dose-and-steady-state-pharmacokinetics-of-orally-administered-crizotinib-in-children-with-solid-tumors-a-report-on-advl0912-from-the-children-s-oncology-group-phase-1-pilot-consortium
#13
Frank M Balis, Patrick A Thompson, Yael P Mosse, Susan M Blaney, Charles G Minard, Brenda J Weigel, Elizabeth Fox
PURPOSE: Characterize the pharmacokinetics of oral crizotinib in children with cancer. METHODS: Sixty-four children with solid tumors or anaplastic large-cell lymphoma (ALCL) enrolled on a phase 1/2 trial of the ALK, MET and ROS1 inhibitor, crizotinib, had pharmacokinetic sampling after the first dose (n = 15) or at steady state (n = 49). Dose levels studied were 100, 130, 165, 215, 280 and 365 mg/m(2)/dose administered twice daily. Two capsule and two oral liquid formulations were used over the course of the trial...
December 28, 2016: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28031719/potential-role-of-immunotherapy-in-advanced-non-small-cell-lung-cancer
#14
REVIEW
Ramon Andrade de Mello, Ana Flávia Veloso, Paulo Esrom Catarina, Sara Nadine, Georgios Antoniou
Immuno checkpoint inhibitors have ushered in a new era with respect to the treatment of advanced non-small-cell lung cancer. Many patients are not suitable for treatment with epidermal growth factor receptor tyrosine kinase inhibitors (eg, gefitinib, erlotinib, and afatinib) or with anaplastic lymphoma kinase inhibitors (eg, crizotinib and ceritinib). As a result, anti-PD-1/PD-L1 and CTLA-4 inhibitors may play a novel role in the improvement of outcomes in a metastatic setting. The regulation of immune surveillance, immunoediting, and immunoescape mechanisms may play an interesting role in this regard either alone or in combination with current drugs...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28024693/the-race-to-target-met-exon-14-skipping-alterations-in-non-small-cell-lung-cancer-the-why-the-how-the-who-the-unknown-and-the-inevitable
#15
REVIEW
Thanyanan Reungwetwattana, Ying Liang, Viola Zhu, Sai-Hong Ignatius Ou
A number of small molecule tyrosine kinase inhibitors (TKIs) have now been approved for the treatment of non-small cell lung cancers (NSCLC), including those targeted against epidermal growth factor receptor, anaplastic lymphoma kinase, and ROS1. Despite a wealth of agents developed to target the receptor tyrosine kinase, MET, clinical outcomes have as yet been disappointing, leading to pessimism about the role of MET in the pathogenesis of NSCLC. However, in recent years, there has been a renewed interest in MET exon 14 alterations as potential drivers of lung cancer...
January 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/28018791/successful-ceritinib-treatment-in-a-man-with-mpe-and-an-alk-fusion-gene-mutation-after-multiple-treatments
#16
Hangping Wei, Fangming Du, Yifang Lu, Juan Wei, Xiaofang Dong
INTRODUCTION: Ceritinib is a second-generation anaplastic lymphoma kinase (ALK) inhibitor. It inhibits two of the most common ALK-mutants that confer resistance to crizotinib. Ceritinib was approved by Food and Drug Administration in April 2014. However, the efficacy of ceritinib in Asian patients have not been widely studied. Decrease of malignant pleural effusion (MPE) has been rarely reported after treatment with ceritinib. CASE DESCRIPTION: A 50-year old man diagnosed with stage IV lung adenocarcinoma presented with MPE and an ALK fusion gene mutation...
2016: SpringerPlus
https://www.readbyqxmd.com/read/28008383/better-to-be-alone-than-in-bad-company-the-antagonistic-effect-of-cisplatin-and-crizotinib-combination-therapy-in-non-small-cell-lung-cancer
#17
Nele Van Der Steen, Christophe Deben, Vanessa Deschoolmeester, An Wouters, Filip Lardon, Christian Rolfo, Paul Germonpré, Elisa Giovannetti, Godefridus J Peters, Patrick Pauwels
AIM: To investigate the potential benefit of combining the cMET inhibitor crizotinib and cisplatin we performed in vitro combination studies. METHODS: We tested three different treatment schemes in four non-small cell lung cancer (NSCLC) cell lines with a different cMET/epidermal growth factor receptor genetic background by means of the sulforhodamine B assay and performed analysis with Calcusyn. RESULTS: All treatment schemes showed an antagonistic effect in all cell lines, independent of the cMET status...
December 10, 2016: World Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28007627/clinical-outcome-of-alk-positive-non-small-cell-lung-cancer-nsclc-patients-with-de-novo-egfr-or-kras-co-mutations-receiving-tyrosine-kinase-inhibitors-tki
#18
Sabine Schmid, Oliver Gautschi, Sacha Rothschild, Michael Mark, Patrizia Froesch, Dirk Klingbiel, Hermann Reichegger, Wolfram Jochum, Joachim Diebold, Früh Martin
BACKGROUND: Non-small cell lung cancer (NSCLC) with de novo anaplastic lymphoma kinase (ALK) rearrangements and epidermal growth factor receptor (EGFR) or Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations co-occur very rarely. Outcomes with tyrosine kinase inhibitors (TKIs) in these patients (pts) are poorly understood. METHODS: Outcomes of pts with metastatic NSCLC de novo co- alterations of ALK/EGFR or ALK/KRAS detected by FISH (ALK) and sequencing (EGFR/KRAS) from six Swiss centres were analysed...
December 19, 2016: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28005438/interactions-of-crizotinib-and-gefitinib-with-organic-anion-transporting-polypeptides-oatp-1b1-oatp1b3-and-oatp2b1-gefitinib-shows-contradictory-interaction-with-oatp1b3
#19
Toshihiro Sato, Hajime Ito, Ayaka Hirata, Takaaki Abe, Nariyasu Mano, Hiroaki Yamaguchi
1. The drug-drug interaction (DDI) mediated by organic anion-transporting polypeptide (OATP)1B1, OATP1B3, and OATP2B1 has a major impact on the hepatic clearance of drugs. The effects of tyrosine kinase inhibitors (TKIs) on OATPs have not been well studied. In the present study, we evaluated the contribution of OATPs to the hepatic uptake of crizotinib and gefitinib and the interaction of those TKIs with OATPs to estimate DDIs. 2. To clarify whether crizotinib and gefitinib were substrates for OATPs, we performed uptake studies...
December 22, 2016: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/27987587/clinical-relevance-of-ros1-rearrangements-detection-in-advanced-squamous-cell-carcinomas
#20
Cécilia Gibelin, Virginie Avrillon, Arnaud De La Fouchardiere, Anne Mc Leer-Florin, Sylvie Lantuejoul, Jérôme Fayette
Non-small cell lung cancers (NSCLCs) have molecular characterization and most druggable genetic and molecular abnormalities, such as EGFR, ERBB2 and BRAF mutations, and ALK and ROS1 rearrangements, have been observed in a subset of adenocarcinomas or large cell carcinomas [1]. Even if these abnormalities are seldom detected in squamous cell carcinomas (SQCC), some rare cases of SQCC have been reported to harbor EGFR, ROS1 or ALK genetic alterations with in some cases a response to targeted therapies [2,3]. Here, we describe a patient with a SQCC harboring ROS1 rearrangement and a response to the target therapy, crizotinib...
December 2016: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
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