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Crizotinib

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https://www.readbyqxmd.com/read/29474558/phase-3-study-of-ceritinib-vs-chemotherapy-in-alk-rearranged-nsclc-patients-previously-treated-with-chemotherapy-and-crizotinib-ascend-5-japanese-subset
#1
Katsuyuki Kiura, Fumio Imamura, Hiroshi Kagamu, Shingo Matsumoto, Toyoaki Hida, Kazuhiko Nakagawa, Miyako Satouchi, Isamu Okamoto, Mitsuhiro Takenoyama, Yasuhito Fujisaka, Takayasu Kurata, Masayuki Ito, Kota Tokushige, Ben Hatano, Makoto Nishio
Background: In the global, Phase 3, ASCEND-5 study, ceritinib improved progression-free survival (PFS) vs chemotherapy in patients with anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer (NSCLC) who had previously progressed on crizotinib and platinum-based chemotherapy. Here, we report efficacy and safety in a subset of Japanese patients from the ASCEND-5 study. Methods: Patients with advanced ALK-rearranged NSCLC received oral ceritinib 750 mg/day or chemotherapy (intravenous pemetrexed 500 mg/m2 or docetaxel 75 mg/m2 [investigator's choice], every 21 days)...
February 21, 2018: Japanese Journal of Clinical Oncology
https://www.readbyqxmd.com/read/29470986/silencing-of-lncrna-hotair-decreases-drug-resistance-of-non-small-cell-lung-cancer-cells-by-inactivating-autophagy-via-suppressing-the-phosphorylation-of-ulk1
#2
Yan Yang, Caiyu Jiang, Yang Yang, Lu Guo, Jiang Huang, Xingren Liu, Chi Wu, Jun Zou
Drug resistance is an important factor leading to the recurrence and metastasis of Non-Small Cell Lung Cancer (NSCLC). Long non-coding RNAs (LncRNAs) play important roles in drug resistance of tumor cells. The aim of our study was to investigate the mechanism of LncRNA-HOTAIR in regulating drug resistance of NSCLC cells. Our data indicated that HOTAIR was overexpressed in NSCLC cell lines. Silencing of HOTAIR decreased cell proliferation and increased apoptosis of NSCLC cells (A549). Besides that, HOTAIR shRNA transfection suppressed drug resistance of A549 cells to Crizotinib by more effectively inhibiting cell viability and promoting apoptosis compared with HOTAIR scramble group...
February 19, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29469073/ros1-rearranged-nonsmall-cell-lung-cancer-and-crizotinib-an-indian-experience
#3
V Noronha, M V Chandrakanth, A P Joshi, V Patil, A Chougule, A Mahajan, A K Janu, R Chanana, K Prabhash
ROS1 rearrangement acts as a driver mutation in 1-2% of NSCLC. Crizotinib is approved in this situation both in treatment naïve and pre-treated patients. Here we report our experience with crizotinib in patients with advanced NSCLC harbouring ROS1 rearrangement. Eleven patients were included in our study. More than half of our patients had associated comorbidities and one fourth of them had a compromised performance status. Out of 11 patients, 5 of them were exposed to crizotinib .The response rates among crizotinib treated patients was 80%...
April 2017: Indian Journal of Cancer
https://www.readbyqxmd.com/read/29468455/evaluation-of-hepatic-impairment-on-pharmacokinetics-and-safety-of-crizotinib-in-patients-with-advanced-cancer
#4
Anthony B El-Khoueiry, John Sarantopoulos, Cindy L O'Bryant, Kristen K Ciombor, Huiping Xu, Melissa O'Gorman, Jayeta Chakrabarti, Tiziana Usari, Bassel F El-Rayes
PURPOSE: This phase 1 study evaluated the effect of hepatic impairment on pharmacokinetics and safety of crizotinib in patients with advanced cancer. METHODS: Patients were dosed according to hepatic function classified by modified National Cancer Institute Organ Dysfunction Working Group criteria and group assignment [normal (A1 and A2), mild (B), moderate (C1 and C2), or severe (D)]. Primary pharmacokinetic endpoints included area under the concentration-time curve as daily exposure (AUCdaily ) and maximum plasma concentration (Cmax ) at steady state...
February 21, 2018: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/29467147/alectinib-for-advanced-alk-positive-non-small-cell-lung-cancer
#5
REVIEW
Ashley C Ly, Jacqueline L Olin, Morgan B Smith
PURPOSE: The pharmacology, pharmacokinetics, clinical efficacy, safety and tolerability, dosage and administration, and place in therapy of alectinib for treatment of patients with non-small-cell lung cancer (NSCLC) are reviewed. SUMMARY: In patients with NSCLC driven by mutations of ALK , the gene coding for anaplastic lymphoma kinase (ALK), treatment with the ALK inhibitor crizotinib has been found to provide median progression-free survival (PFS) of 10.9 months; however, therapeutic failures and tumor progression to brain metastases are common with crizotinib use, prompting research to find more potent and tolerable ALK inhibitors that target major oncogenic drivers of NSCLC...
February 21, 2018: American Journal of Health-system Pharmacy: AJHP
https://www.readbyqxmd.com/read/29466887/access-to-anti-cancer-drugs-in-india-is-there-a-need-to-revise-reimbursement-policies
#6
Gertruud Haitsma, Himanshu Patel, Parthasarathi Gurumurthy, Maarten J Postma
BACKGROUND: The aim of this study was to examine the access of Indian cancer patients to optimum cancer care under selected government schemes by reviewing reimbursement schemes for cancer care in India. METHODS: All cancer care reimbursement schemes in India were identified and three highly utilized schemes (VAS, RAS, CMCHS) were selected. Quality of breast, colorectal, lung, head & neck, and gastric cancer care was reviewed with respect to NCCN guidelines...
February 22, 2018: Expert Review of Pharmacoeconomics & Outcomes Research
https://www.readbyqxmd.com/read/29460035/frequent-genomic-alterations-and-better-prognosis-among-young-patients-with-non-small-cell-lung-cancer-aged-40-years-or-younger
#7
X Pan, T Lv, F Zhang, H Fan, H Liu, Y Song
BACKGROUND: The subgroup of young patients with non-small-cell lung cancer (NSCLC) is poorly understood. We retrospectively studied the clinical characteristics, gene mutations, and outcomes of patients with NSCLC (aged ≤ 40 years). RESULTS: Of the 7494 patients with lung cancer diagnosed from February 2001 to October 2016, 252 aged ≤ 40 years showed NSCLC. We divided their cases into non-squamous cell carcinoma and squamous cell carcinoma groups according to their histology results...
February 19, 2018: Clinical & Translational Oncology
https://www.readbyqxmd.com/read/29458783/precision-medicine-in-alk-rearranged-nsclc-a-rapidly-evolving-scenario
#8
REVIEW
Alfredo Addeo, Fabrizio Tabbò, Tim Robinson, Lucio Buffoni, Silvia Novello
IMPORTANCE: The identification of anaplastic lymphoma kinase (ALK) rearrangements in 2-5% of non-small cell lung cancer (NSCLC) patients led to the rapid clinical development of its oral tyrosine kinase inhibitor (TKI). Crizotinib was the first ALK inhibitor approved and utilised in the treatment of ALK+ NSCLC patients in the second line setting first and subsequently in the first line one. Since then many other ALK inhibitors have been developed (ceritinib, alectinib, brigatinib, lorlatinib,etc) and the treatment paradigm of these patients has considerably drifted...
February 2018: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/29458286/cost-effectiveness-of-ceritinib-in-previously-untreated-anaplastic-lymphoma-kinase-positive-metastatic-non-small-cell-lung-cancer-in-the-united-states
#9
Zheng-Yi Zhou, Alex Mutebi, Simeng Han, Arielle G Bensimon, Marie Louise Ricculli, Jipan Xie, Anand Dalal, Ken Culver
AIMS: To assess the cost-effectiveness of first-line ceritinib versus crizotinib and platinum doublet chemotherapy for anaplastic lymphoma kinase (ALK)-positive metastatic non-small cell lung cancer (NSCLC) from a US third-party payer's perspective. MATERIALS AND METHODS: A partitioned survival model with three health states (stable disease, progressive disease, death) was developed over a 20-year time horizon. Ceritinib's efficacy inputs (progression-free and overall survival) were estimated from ASCEND-4; parametric survival models extrapolated data beyond the trial period...
February 19, 2018: Journal of Medical Economics
https://www.readbyqxmd.com/read/29456853/crizotinib-associated-toxic-epidermal-necrolysis-in-an-alk-positive-advanced-nsclc-patient
#10
Shaoyu Yang, Liming Wu, Xin Li, Jie Huang, Jianbo Zhong, Xueqin Chen
Crizotinib is an oral small-molecule inhibitor of anaplastic lymphoma kinase (ALK) tyrosine-kinase that has been approved for treating patients with advanced echinoderm microtubule associated protein like 4-ALK rearranged non-small-cell lung cancer (NSCLC). Toxic epidermal necrolysis (TEN) is a rare adverse event associated with crizotinib. The present study reported a case of a 75-year-old Chinese male patient with advanced NSCLC with ALK fusion, who developed TEN after 56 days of crizotinib treatment and demised due to this dermatological adverse event...
March 2018: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/29455675/the-function-and-therapeutic-targeting-of-anaplastic-lymphoma-kinase-alk-in-non-small-cell-lung-cancer-nsclc
#11
REVIEW
Brandon Golding, Anita Luu, Robert Jones, Alicia M Viloria-Petit
Lung cancer is the leading cause of death by cancer in North America. A decade ago, genomic rearrangements in the anaplastic lymphoma kinase (ALK) receptor tyrosine kinase were identified in a subset of non-small cell lung carcinoma (NSCLC) patients. Soon after, crizotinib, a small molecule ATP-competitive ALK inhibitor was proven to be more effective than chemotherapy in ALK-positive NSCLC patients. Crizotinib and two other ATP-competitive ALK inhibitors, ceritinib and alectinib, are approved for use as a first-line therapy in these patients, where ALK rearrangement is currently diagnosed by immunohistochemistry and in situ hybridization...
February 19, 2018: Molecular Cancer
https://www.readbyqxmd.com/read/29455642/role-and-targeting-of-anaplastic-lymphoma-kinase-in-cancer
#12
REVIEW
Carminia Maria Della Corte, Giuseppe Viscardi, Raimondo Di Liello, Morena Fasano, Erika Martinelli, Teresa Troiani, Fortunato Ciardiello, Floriana Morgillo
Anaplastic lymphoma kinase (ALK) gene activation is involved in the carcinogenesis process of several human cancers such as anaplastic large cell lymphoma, lung cancer, inflammatory myofibroblastic tumors and neuroblastoma, as a consequence of fusion with other oncogenes (NPM, EML4, TIM, etc) or gene amplification, mutation or protein overexpression. ALK is a transmembrane tyrosine kinase receptor that, upon ligand binding to its extracellular domain, undergoes dimerization and subsequent autophosphorylation of the intracellular kinase domain...
February 19, 2018: Molecular Cancer
https://www.readbyqxmd.com/read/29455091/an-uplc-ms-ms-method-to-determine-ct-707-and-its-two-metabolites-in-plasma-of-alk-positive-advanced-non-small-cell-lung-cancer-patients
#13
Cheng Cui, Pei Hu, Ji Jiang, Fansheng Kong, Hong Luo, Qian Zhao
CT-707, a mutant-selective inhibitor of an important cancer target, anaplastic lymphoma kinase (ALK), is designed to be a targeted therapeutic agent for non-small cell lung cancer (NSCLC) patients harboring ALK active and crizotinib resistant mutations. A rapid and sensitive ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed and validated for the determination of CT-707 and its two metabolites (M1 and M2) in human plasma. The samples were purified by solid phase extraction (SPE) and separated on a BEH C18 column (2...
January 31, 2018: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/29451020/the-brigatinib-experience-a-new-generation-of-therapy-for-alk-positive-non-small-cell-lung-cancer
#14
Idoroenyi Amanam, Rohan Gupta, Isa Mambetsariev, Ravi Salgia
Lung cancer remains the leading cause of cancer deaths in the world with 1.69 million deaths in 2015. A total of 85% of lung cancer cases are non-small-cell lung cancers (NSCLCs). Driver mutations associated with anaplastic lymphoma kinase (ALK) have been identified in a variety of malignancies, including NSCLC. An ALK inhibitor (crizotinib, ceritinib and alectinib) is the preferred therapeutic approach to those advanced ALK fusion variant-positive NSCLC patients. Brigatinib, a next-generation ALK inhibitor, shows promising activity in ALK-rearranged NSCLC that have previously received crizotinib with response rates in ALTA ranging from 42-50%, intracranial response 42-67% and median progression-free survival 9...
February 16, 2018: Future Oncology
https://www.readbyqxmd.com/read/29450203/real-life-experience-of-ceritinib-in-crizotinib-pretreated-alk-advanced-non-small-cell-lung-cancer-patients
#15
Jacques Cadranel, Alexis B Cortot, Hervé Lena, Bertrand Mennecier, Pascal Do, Eric Dansin, Julien Mazieres, Christos Chouaid, Maurice Perol, Fabrice Barlesi, Gilles Robinet, Sylvie Friard, Luc Thiberville, Clarisse Audigier-Valette, Alain Vergnenegre, Virginie Westeel, Khemaies Slimane, Alexandru Buturuga, Denis Moro-Sibilot, Benjamin Besse
Here we report our experience of ceritinib in crizotinib-pretreated patients with anaplastic lymphoma kinase ( ALK ) positive ( ALK + ) non-small cell lung cancer (NSCLC) in a French temporary authorisation for use (TAU) study. The French TAU study included crizotinib-pretreated patients with advanced ALK + or ROS proto-oncogene 1 positive ( ROS1 + ) tumours. Patients received oral ceritinib (750 mg·day -1 as a starting dose) and best tumour response (as evaluated by the investigator) and safety were reported every 3 months...
January 2018: ERJ Open Research
https://www.readbyqxmd.com/read/29444468/a-major-component-of-vitamin-e-%C3%AE-tocopherol-inhibits-the-anti-tumor-activity-of-crizotinib-against-cells-transformed-by-eml4-alk
#16
Yuki Uchihara, Takayuki Kidokoro, Kenji Tago, Tadahiko Mashino, Hiroomi Tamura, Megumi Funakoshi-Tago
Crizotinib is an inhibitor of anaplastic lymphoma kinase (ALK) and is of significant therapeutic benefit to patients with non-small cell lung cancer (NSCLC) harboring the EML4-ALK fusion gene. In the present study, we demonstrated that α-tocopherol, a major component of vitamin E, attenuated the effects of crizotinib independently of its anti-oxidant properties. α-Tocopherol significantly inhibited crizotinib-induced apoptosis in cells transformed by EML4-ALK. It also effectively attenuated the crizotinib-induced inhibition of EML4-ALK and its downstream molecules, STAT3 and ERK, and suppressed the inhibitory effects of crizotinib on EML4-ALK-mediated transformation in the focus formation assay...
February 11, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29440379/targeting-the-cmet-pathway-augments-radiation-response-without-adverse-effect-on-hearing-in-nf2-schwannoma-models
#17
Yingchao Zhao, Pinan Liu, Na Zhang, Jie Chen, Lukas D Landegger, Limeng Wu, Fu Zhao, Yanxia Zhao, Yanling Zhang, Jing Zhang, Takeshi Fujita, Anat Stemmer-Rachamimov, Gino B Ferraro, Hao Liu, Alona Muzikansky, Scott R Plotkin, Konstantina M Stankovic, Rakesh K Jain, Lei Xu
Neurofibromatosis type II (NF2) is a disease that needs new solutions. Vestibular schwannoma (VS) growth causes progressive hearing loss, and the standard treatment, including surgery and radiotherapy, can further damage the nerve. There is an urgent need to identify an adjunct therapy that, by enhancing the efficacy of radiation, can help lower the radiation dose and preserve hearing. The mechanisms underlying deafness in NF2 are still unclear. One of the major limitations in studying tumor-induced hearing loss is the lack of mouse models that allow hearing testing...
February 9, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29437006/enteral-administration-of-tkis-report-of-a-response-to-ceritinib-in-an-alk-positive-nsclc-patient-and-literature-review
#18
Francesco Facchinetti, Paola Bordi, Paola Bini, Livia Bidin, Roberta Camisa, Marcello Tiseo
INTRODUCTION: Several reports attest the feasibility and the favorable outcomes of kinase inhibitors administration through feeding tubes or percutaneous endoscopic gastrostomies (PEG), mainly in non-small cell lung cancer (NSCLC) patients exposed to first-generation compounds. Here we present the case of an ALK-positive NSCLC patient who achieved cerebral and extra-cranial disease response with ceritinib (a novel ALK inhibitor) administered through a nasogastric tube (NGT). We moreover provide a review gathering clinical successes obtained with targeted agents intake through NGT or PEG...
February 12, 2018: Current Drug Targets
https://www.readbyqxmd.com/read/29420337/anticancer-effect-of-s-crizotinib-on-osteosarcoma-cells-by-targeting-mth1-and-activating-reactive-oxygen-species
#19
Xiangcheng Qing, Zengwu Shao, Xiao Lv, Feifei Pu, Feng Gao, Lei Liu, Deyao Shi
MTH1 has become a new rising star in the field of 'cancer phenotypic lethality' and can be targeted in many kinds of tumors. This study aimed to explore the anticancer effect of MTH1-targeted drug (S)-crizotinib on osteosarcoma (OS) cells. We detected MTH1 expression in OS tissues and cells using immunohistochemistry and western blot. The effects of MTH1 on OS cell viability were explored using the siRNA technique and CCK8. The anticancer effects of the MTH1-targeted drug (S)-crizotinib on OS cells were explored by in-vitro assays...
February 7, 2018: Anti-cancer Drugs
https://www.readbyqxmd.com/read/29416931/single-oral-dose-acute-and-subacute-toxicity-of-a-c-met-tyrosine-kinase-inhibitor-and-cdk-4-6-inhibitor-combination-drug-therapy
#20
Brian Smith, Yi-Hsin Hsu, Rene Flores, Mihai Gagea, Suzanne Craig, Mien-Chie Hung
c-MET inhibitor, crizotinib, and CDK 4/6 inhibitor, palbociclib, have been evaluated in combination as cancer treatment in vitro. Because the toxicological data for the combination of these drugs is limited, we investigated the toxicity of the crizotinib and palbociclib combination in 80 ICR (CD-1) mice (average age = ~20 weeks). Treatments were arranged as a 2 × 2 × 2 factorial and included sex (female vs. male), crizotinib (0 or 4 mg), and palbociclib (0 or 1 mg). Drugs were administered to mice by oral gavage 24 hours (n = 40) and 7 days (n = 40) prior to the collection of blood and tissue samples to determine serum chemistry, hematology, and histopathology...
2018: American Journal of Cancer Research
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