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https://www.readbyqxmd.com/read/28195235/lung-cancer-ceritinib-is-superior-to-frontline-chemotherapy
#1
Peter Sidaway
No abstract text is available yet for this article.
February 14, 2017: Nature Reviews. Clinical Oncology
https://www.readbyqxmd.com/read/28193771/ceritinib-bests-chemo-for-untreated-alk-nsclc
#2
(no author information available yet)
Patients with ALK-positive non-small cell lung cancer may soon have a new first-line treatment option in ceritinib, which outperformed chemotherapy in a phase III study. However, toxicity issues remain a problem for ceritinib, and another next-generation ALK inhibitor, alectinib, is more likely to become the drug of choice for untreated patients.
February 13, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28152720/comparison-of-real-world-acute-care-interventions-aci-in-patients-pts-with-advanced-non-small-cell-lung-cancer-adv-nsclc-treated-with-chemotherapy-versus-targeted-therapies
#3
Beata Korytowsky, Menaka Bhor, Ken Tuell, Bruce A Feinberg
: 37 Background: This analysis compared the frequency of ACI for any cause (emergency room [ER] visits, hospitalizations, and readmissions) to better understand the burden of treatment in adv NSCLC pts treated with chemotherapy (chemo) vs targeted therapy (TT). METHODS: Using Inovalon's MORE(2) Registry claims data, adv NSCLC pts treated with antineoplastics identified by ICD-9 codes from July 2013-2014 were selected. Inclusion: pts >18 y who received first-line (1L) systemic therapy within 6 mo of diagnosis...
March 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28126333/first-line-ceritinib-versus-platinum-based-chemotherapy-in-advanced-alk-rearranged-non-small-cell-lung-cancer-ascend-4-a-randomised-open-label-phase-3-study
#4
Jean-Charles Soria, Daniel S W Tan, Rita Chiari, Yi-Long Wu, Luis Paz-Ares, Juergen Wolf, Sarayut L Geater, Sergey Orlov, Diego Cortinovis, Chong-Jen Yu, Maximillian Hochmair, Alexis B Cortot, Chun-Ming Tsai, Denis Moro-Sibilot, Rosario G Campelo, Tracey McCulloch, Paramita Sen, Margaret Dugan, Serafino Pantano, Fabrice Branle, Cristian Massacesi, Gilberto de Castro
BACKGROUND: The efficacy of ceritinib in patients with untreated anaplastic lymphoma kinase (ALK)-rearranged non-small-cell lung cancer (NSCLC) is not known. We assessed the efficacy and safety of ceritinib versus platinum-based chemotherapy in these patients. METHODS: This randomised, open-label, phase 3 study in untreated patients with stage IIIB/IV ALK-rearranged non-squamous NSCLC was done in 134 centres across 28 countries. Eligible patients were assigned via interactive response technology to oral ceritinib 750 mg/day or platinum-based chemotherapy ([cisplatin 75 mg/m(2) or carboplatin AUC 5-6 plus pemetrexed 500 mg/m(2)] every 3 weeks for four cycles followed by maintenance pemetrexed); randomisation was stratified by World Health Organization performance status (0 vs 1-2), previous neoadjuvant or adjuvant chemotherapy, and presence of brain metastases as per investigator's assessment at screening...
January 23, 2017: Lancet
https://www.readbyqxmd.com/read/28077299/anaplastic-lymphoma-kinase-alk-inhibitors-in-the-treatment-of-alk-driven-lung-cancers
#5
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/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"...
February 2017: 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/28031719/potential-role-of-immunotherapy-in-advanced-non-small-cell-lung-cancer
#12
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/28018791/successful-ceritinib-treatment-in-a-man-with-mpe-and-an-alk-fusion-gene-mutation-after-multiple-treatments
#13
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/27986745/dual-alk-and-cdk4-6-inhibition-demonstrates-on-target-synergy-against-neuroblastoma
#14
Andrew Wood, Kateryna Krytska, Hannah T Ryles, Nicole R Infarinato, Renata Sano, Theodore D Hansel, Lori S Hart, Frederick King, Timothy R Smith, Edward Ainscow, Kathryn B Grandinetti, Tove Tuntland, Sunkyu Kim, Giordano Caponigro, You-Qun He, Shiva Krupa, Nanxin Li, Jennifer Harris, Yael P Mosse
PURPOSE: Anaplastic Lymphoma Kinase (ALK) is the most frequently mutated oncogene in the pediatric cancer neuroblastoma. We performed an in vitro screen for synergistic drug combinations that target neuroblastomas with mutations in ALK to determine if drug combinations could enhance anti-tumor efficacy. EXPERIMENTAL DESIGN: We screened combinations of eight molecularly targeted agents against seventeen comprehensively characterized human neuroblastoma-derived cell lines...
December 16, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27969537/ps01-70-ceritinib-dosing-patterns-and-outcomes-of-patients-with-alk-nsclc-in-a-real-world-practice-in-the-united-states-topic-medical-oncology
#15
Edmond Bendaly, Anand Dalal, Kenneth Culver, Philip J Galebach, Iryna Bocharova, Rebekah Foster, Gero Struebbe, Annie Guerin
No abstract text is available yet for this article.
November 2016: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/27969450/mini01-01-whole-body-and-intracranial-efficacy-of%C3%A2-ceritinib-in-alk-inhibitor-na%C3%A3-ve-patients-with-alk-nsclc-and-brain-metastases-results-of-ascend-1-and-3-topic-medical-oncology
#16
Alice T Shaw, David R Spigel, Daniel S-W Tan, Dong-Wan Kim, Ranee Mehra, Sergey Orlov, Keunchil Park, Chong-Jen Yu, Tony Mok, Makoto Nishio, Giorgio Scagliotti, Santosh Sutradhar, Dajana Cesic, Enriqueta Felip
No abstract text is available yet for this article.
November 2016: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/27960155/stimulation-of-suicidal-erythrocyte-death-by-ceritinib-treatment-of-human-erythrocytes
#17
Abdulla Al Mamun Bhuyan, Elena Signoretto, Rosi Bissinger, Florian Lang
BACKGROUND/AIMS: The anaplastic lymphoma kinase (ALK) inhibitor ceritinib is utilized for the treatment of ALK positive non-small cell lung carcinoma. Side effects of the drug include decrease of blood hemoglobin concentration. Possible causes of anemia include stimulation of suicidal erythrocyte death or eryptosis, which is characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine translocation to the erythrocyte surface. Signaling of eryptosis includes increase of cytosolic Ca2+ activity ([Ca2+]i), oxidative stress, ceramide, staurosporine sensitive protein kinase C, SB203580 sensitive p38 kinase, D4476 sensitive casein kinase 1, and zVAD sensitive caspases...
2016: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/27922734/population-pharmacokinetics-of-ceritinib-in-adult-patients-with-tumors-characterized-by-genetic-abnormalities-in-anaplastic-lymphoma-kinase
#18
Ying Hong, Vanessa Q Passos, Pai-Hsi Huang, Yvonne Y Lau
Ceritinib is a second-generation selective and potent oral anaplastic lymphoma kinase (ALK) inhibitor approved for ALK-positive advanced non-small cell lung cancer previously treated with crizotinib. Population pharmacokinetic (PK) analysis was performed to describe the PK of ceritinib and was used to evaluate the covariate effects on systemic exposure at its label dose (750 mg orally once daily). Ceritinib concentration-time data from 4 clinical studies were described by a 1-compartment model with delayed first-order absorption and time-dependent elimination...
December 6, 2016: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/27915169/replacing-the-terminal-piperidine-in-ceritinib-with-aliphatic-amines-confers-activities-against-crizotinib-resistant-mutants-including-g1202r
#19
Gangadhar Rao Mathi, Chung Hyo Kang, Heung Kyoung Lee, Raghavendra Achary, Ha-Yeon Lee, Joo-Youn Lee, Jae Du Ha, Sunjoo Ahn, Chi Hoon Park, Chong Ock Lee, Jong Yeon Hwang, Chang-Soo Yun, Hee Jung Jung, Sung Yun Cho, Hyoung Rae Kim, Pilho Kim
The piperidine fragment in ceritinib was replaced with diverse aliphatic amines to improve inherent resistance issues of ceritinib. While most of the prepared compounds exhibit as similar in vitro activities as ceritinib, compound 10 shows encouraging activities against wild-type ALK as well as crizotinib-resistant mutants including extremely resistant G1202R mutant with an IC50 of 1.8 nM. Furthermore, pharmacokinetic profiles of 10 is apparently better than that of ceritinib. In murine xenograft studies, compound 10 turns out to be as active as ceritinib, suggesting that further optimization of 10 may lead to clinical candidates overcoming ALK mutant issues...
November 24, 2016: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27912826/diagnosis-and-treatment-of-anaplastic-lymphoma-kinase-positive-non-small-cell-lung-cancer
#20
REVIEW
Kathryn C Arbour, Gregory J Riely
Anaplastic lymphoma kinase (ALK) gene rearrangements occur in a small portion of patients with non-small cell lung cancer (NSCLC). These gene rearrangements lead to constitutive activation of the ALK kinase and subsequent ALK-driven tumor formation. Patients with tumors harboring such rearrangements are highly sensitive to ALK inhibitors, such as crizotinib, ceritinib, and alectinib. Resistance to these kinase inhibitors occurs through several mechanisms, resulting in ongoing clinical challenges. This review summarizes the biology of ALK-positive lung cancer, methods for diagnosing ALK-positive NSCLC, current FDA-approved ALK inhibitors, mechanisms of resistance to ALK inhibition, and potential strategies to combat resistance...
February 2017: Hematology/oncology Clinics of North America
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