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https://www.readbyqxmd.com/read/28444429/hypopharyngeal-and-upper-esophageal-ulceration-after-cervical-spine-radiotherapy-concurrent-with-crizotinib
#1
Marcus H Zimmermann, Gabriele Beckmann, Pius Jung, Michael Flentje
Herein, the authors describe the case of a 31-year-old female patient with primary metastatic adenocarcinoma of the lung referred for radiation therapy of newly diagnosed intramedullary spinal cord metastasis at C4/5 and an adjacent osteolytic lesion. Radiotherapy of the cervical spine level C3 to C5, including the whole vertebra, was performed with 30 Gy in 10 fractions. The patient's systemic therapy with crizotinib 250 mg twice daily was continued. After 8 fractions of radiation the patient developed increasing dysphagia...
April 25, 2017: Strahlentherapie und Onkologie: Organ der Deutschen Röntgengesellschaft ... [et Al]
https://www.readbyqxmd.com/read/28442018/-recent-advances-and-prospect-of-advanced-non-small-cell-lung-cancer-targeted-%C3%A2-therapy-focus-on-small-molecular-tyrosine-kinase-inhibitors
#2
Guowei Zhang, Huijuan Wang, Zhiyong Ma
At present the treatment of advanced non-small cell lung cancer enters a targeted era and develops rapidly. New drugs appear constantly. Small molecular tyrosine kinase inhibitors have occupied the biggest piece of the territory, which commonly have a clear biomarker as predictor, and show remarkable effect in specific molecular classification of patients. The epidermal growth factor tyrosine kinase inhibitors such as gefitinib, erlotinib, icotinib and anaplastic lymphoma kinase tyrosine kinase inhibitors crizotinib have brought a milestone advance...
April 20, 2017: Zhongguo Fei Ai za Zhi, Chinese Journal of Lung Cancer
https://www.readbyqxmd.com/read/28438234/significant-radiologic-response-of-pancreatic-metastasis-after-targeted-therapy-of-ceritinib-ldk378-for-alk-rearranged-lung-adenocarcinoma-presenting-with-hyperglycemia
#3
Jing Zheng, Jianya Zhou, Yanping Zhu, Qian Shen, Jianying Zhou
Pancreatic metastasis from non-small cell lung cancer (NSCLC) is usually asymptomatic or presents with abdominal pain, acute pancreatitis, or jaundice. A lung primary is associated with worse survival compared to pancreatic metastases from other organs. Surgical treatment of solitary metastasis to the pancreas from NSCLC has been reviewed in several studies, one of which had a notable disease-free interval. To our knowledge, there are no prior reports of targeted therapy of pancreatic metastasis of NSCLC followed by a significant response...
April 14, 2017: Oncology Research
https://www.readbyqxmd.com/read/28437395/global-survey-of-the-immunomodulatory-potential-of-common-drugs
#4
Gregory I Vladimer, Berend Snijder, Nikolaus Krall, Johannes W Bigenzahn, Kilian V M Huber, Charles-Hugues Lardeau, Kumar Sanjiv, Anna Ringler, Ulrika Warpman Berglund, Monika Sabler, Oscar Lopez de la Fuente, Paul Knöbl, Stefan Kubicek, Thomas Helleday, Ulrich Jäger, Giulio Superti-Furga
Small-molecule drugs may complement antibody-based therapies in an immune-oncology setting, yet systematic methods for the identification and characterization of the immunomodulatory properties of these entities are lacking. We surveyed the immumomodulatory potential of 1,402 small chemical molecules, as defined by their ability to alter the cell-cell interactions among peripheral mononuclear leukocytes ex vivo, using automated microscopy and population-wide single-cell image analysis. Unexpectedly, ∼10% of the agents tested affected these cell-cell interactions differentially...
April 24, 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/28435288/the-activity-safety-and-evolving-role-of-brigatinib-in-patients-with-alk-rearranged-non-small-cell-lung-cancers
#5
REVIEW
Joshua K Sabari, Fernando C Santini, Alison M Schram, Isabella Bergagnini, Ruqin Chen, Chebli Mrad, W Victoria Lai, Kathryn C Arbour, Alexander Drilon
Brigatinib (AP26113) is a dimethylphosphine oxide group-containing tyrosine kinase inhibitor (TKI) constructed around a bisanilinopyrimidine scaffold with potent activity against the anaplastic lymphoma kinase (ALK) and several other targets. Despite the activity of first- and second-generation ALK inhibitors in advanced ALK-rearranged lung cancers, the development of acquired resistance represents an ongoing challenge. Later generation ALK inhibitors such as brigatinib are important potential tools in the management of patients with acquired resistance characterized by continued dependency on ALK...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28432815/immunoassays-for-the-quantification-of-alk-and-phosphorylated-alk-support-the-evaluation-of-on-target-alk-inhibitors-in-neuroblastoma
#6
Elizabeth R Tucker, Jennifer R Tall, Laura S Danielson, Sharon Gowan, Yann Jamin, Simon P Robinson, Udai Banerji, Louis Chesler
Targeted inhibition of Anaplastic Lymphoma Kinase (ALK) is a successful approach for the treatment of many ALK-aberrant malignancies, however the presence of resistant mutations necessitates both the development of more potent compounds and pharmacodynamic methods with which to determine their efficacy. We describe immunoassays designed to quantitate phosphorylation of ALK, and their use in preclinical models of neuroblastoma, a pediatric malignancy in which gain-of-function ALK mutations predict a poor overall outcome to conventional treatment...
April 22, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28427213/clinical-benefit-of-continuing-crizotinib-therapy-after-initial-disease-progression-in-chinese-patients-with-advanced-alk-rearranged-non-small-cell-lung-cancer
#7
Xiangchan Hong, Qi Chen, Lingyu Ding, Ying Liang, Ningning Zhou, Wenfeng Fang, Xinru Chen, Haiying Wu
PURPOSE: Although most patients with ALK-positive non‒small-cell lung cancer (NSCLC) who benefit from treatment with crizotinib ultimately develop progressive disease (PD), continuing crizotinb beyond the initial PD (CBPD) in these patients may be beneficial. In this study, we investigated whether Chinese patients with advanced ALK-positive NSCLC benefit from CBPD, and whether any factors are predictive of a longer post-initial progression-free survival time (PFS2). MATERIALS AND METHODS: Data on 33 patients with ALK-positive NSCLC who achieved disease control with crizotinib were analyzed retrospectively...
March 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28427172/the-amelioration-of-cartilage-degeneration-by-photo-crosslinked-gelha-hydrogel-and-crizotinib-encapsulated-chitosan-microspheres
#8
Pengfei Chen, Sheng Mei, Chen Xia, Ren Zhu, Yichuan Pang, Jiying Wang, Jianfeng Zhang, Fangchun Shao, Shunwu Fan
The present study aimed to investigate the synergistic therapeutic effect of decreaseing cartilage angiogenesis via exposure to crizotinib encapsulated by chitosan microspheres and photo-crosslinked hydrogel, with the goal of evaluating crizotinib as a treatment for osteoarthritis. First, we developed and evaluated the characteristics of hydrogels and chitosan microspheres. Next, we measured the effect of crizotinib on the cartilage degeneration induced by interleukin-1β in chondrocytes. Crizotinib ameliorated the pathological changes induced by interleukin-1β via its anti-angiogenesis function...
February 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28427013/the-accelerated-path-of-ceritinib-translating-pre-clinical-development-into-clinical-efficacy
#9
REVIEW
Tony S K Mok, Lucio Crino, Enriqueta Felip, Ravi Salgia, Tommaso De Pas, Daniel S W Tan, Laura Q M Chow
The discovery of anaplastic lymphoma kinase (ALK)-rearranged non-small-cell lung cancer (NSCLC) in 2007 led to the development and subsequent approval of the ALK inhibitor crizotinib in 2011. However, despite its clinical efficacy, resistance to crizotinib invariably develops. There is now a next generation of ALK inhibitors, including two that have been approved-ceritinib and alectinib-and others that are in development-brigatinib, lorlatinib and X-396. Ceritinib and the other next-generation ALK inhibitors are more potent than crizotinib and can overcome tumor cell resistance mechanisms...
March 30, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28423535/overall-survival-with-crizotinib-and-next-generation-alk-inhibitors-in-alk-positive-non-small-cell-lung-cancer-ifct-1302-clinalk-a-french-nationwide-cohort-retrospective-study
#10
Michaël Duruisseaux, Benjamin Besse, Jacques Cadranel, Maurice Pérol, Bertrand Mennecier, Laurence Bigay-Game, Renaud Descourt, Eric Dansin, Clarisse Audigier-Valette, Lionel Moreau, José Hureaux, Remi Veillon, Josiane Otto, Anne Madroszyk-Flandin, Alexis Cortot, François Guichard, Pascaline Boudou-Rouquette, Alexandra Langlais, Pascale Missy, Franck Morin, Denis Moro-Sibilot
Overall survival (OS) with the anaplastic lymphoma kinase (ALK) inhibitor (ALKi) crizotinib in a large population of unselected patients with ALK-positive non-small-cell lung cancer (NSCLC) is not documented. We sought to assess OS with crizotinib in unselected ALK-positive NSCLC patients and whether post-progression systemic treatments affect survival outcomes.ALK-positive NSCLC patients receiving crizotinib in French expanded access programs or as approved drug were enrolled. We collected clinical and survival data, RECIST-defined progressive disease (PD) and post-PD systemic treatment efficacy...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28419723/characteristics-and-outcomes-of-alk-non-small-cell-lung-cancer-patients-in-korea
#11
Sung Hee Lim, Kyung Ah Yoh, Jong Seok Lee, Myung-Ju Ahn, Yu Jung Kim, Se Hyun Kim, Jie Zhang, Dony Patel, Elyse Swallow, Andrew Kageleiry, Philip Galebach, Dongyeol Lee, Karen Stein, Ravi Degun, Keunchil Park
AIM: This study aimed to describe characteristics, treatment patterns and survival among Korean patients diagnosed with locally advanced or metastatic anaplastic lymphoma kinase (ALK)+ non-small cell lung cancer (NSCLC). METHODS: A retrospective patient chart review was conducted in major cancer centers in Korea in 2014-2015. Participating physicians reviewed patient charts and reported characteristics, treatment patterns, clinician-defined progression-free survival (PFS) and overall survival (OS) of ALK+ locally advanced or metastatic NSCLC patients...
April 16, 2017: Asia-Pacific Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28409069/efficiency-of-crizotinib-on-an-alk-positive-inflammatory-myofibroblastic-tumor-of-the-central-nervous-system-a-case-report
#12
Anas Chennouf, Elizabeth Arslanian, David Roberge, France Berthelet, Michel Bojanowski, Jean-Paul Bahary, Laura Masucci, Karl Belanger, Marie Florescu, Philip Wong
Inflammatory myofibroblastic tumors (IMT) of the central nervous system (CNS) are rare entities that have a predilection for local recurrences. Approximately half of the inflammatory myofibroblastic tumors contain translocations that result in the over-expression of the anaplastic lymphoma kinase (ALK) gene. We hereby present the case of a patient diagnosed with a left parieto-occipital IMT that recurred after multiple surgeries and radiotherapy. Immuno-histochemical examination of the tumor demonstrated ALK overexpression and the presence of an ALK rearrangement observed in lung cancers...
March 2, 2017: Curēus
https://www.readbyqxmd.com/read/28408617/treatment-paradigms-for-advanced-non-small-cell-lung-cancer-at-academic-medical-centers-involvement-in-clinical-trial-endpoint-design
#13
Charu Aggarwal, Hossein Borghaei
Based on the positive results of various clinical trials, treatment options for non-small cell lung cancer (NSCLC) have expanded greatly over the last 25 years. While regulatory approvals of chemotherapeutic agents for NSCLC have largely been based on improvements in overall survival, recent approvals of many targeted agents for NSCLC (afatinib, crizotinib, ceritinib, osimertinib) have been based on surrogate endpoints such as progression-free survival and objective response. As such, selection of appropriate clinical endpoints for examining the efficacy of investigational agents for NSCLC is of vital importance in clinical trial design...
April 13, 2017: Oncologist
https://www.readbyqxmd.com/read/28407036/the-clinical-impact-of-an-eml4-alk-variant-on-survival-following-crizotinib-treatment-in-patients-with-advanced-alk-rearranged-non-small-cell-lung-cancer
#14
Seyoung Seo, Chang Gok Woo, Dae Ho Lee, Jene Choi
No abstract text is available yet for this article.
April 12, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28405961/treatment-patterns-and-early-outcomes-of-alk-positive-non-small-cell-lung-cancer-patients-receiving-ceritinib-a-chart-review-study
#15
Edmond Bendaly, Anand A Dalal, Kenneth Culver, Philip Galebach, Iryna Bocharova, Rebekah Foster, Medha Sasane, Alexander R Macalalad, Annie Guérin
INTRODUCTION: This study aimed to provide the first real-world description of the characteristics, treatments, dosing patterns, and early outcomes of patients with ALK-positive non-small cell lung cancer (NSCLC) who received ceritinib in US clinical practice. METHODS: US oncologists provided data from medical charts of adult patients diagnosed with locally advanced or metastatic ALK-positive NSCLC who received ceritinib following crizotinib. Patient characteristics, treatment patterns, ceritinib dosing, early outcomes, and occurrence of gastrointestinal adverse events (AEs) by dose and instructions on food intake were assessed, and Kaplan-Meier analysis was used to describe clinician-defined progression-free survival (PFS) on ceritinib...
April 12, 2017: Advances in Therapy
https://www.readbyqxmd.com/read/28398575/crizotinib-from-discovery-to-accelerated-development-to-front-line-treatment
#16
F Blackhall, F Cappuzzo
No abstract text is available yet for this article.
April 6, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28374971/a-large-single-center-real-world-study-of-clinicopathological-characteristics-and-treatment-in-advanced-alk-positive-non-small-cell-lung-cancer
#17
Gang Chen, Xi Chen, Yaxiong Zhang, Fang Yan, Wenfeng Fang, Yunpeng Yang, Shaodong Hong, Siyu Miao, Manli Wu, Xiaodan Huang, Youli Luo, Cong Zhou, Run Gong, Yan Huang, Ningning Zhou, Hongyun Zhao, Li Zhang
Crizotinib has achieved astonishing success in advanced non-small-cell lung cancer (NSCLC) patients harboring anaplastic lymphoma kinase (ALK) rearrangement. However, no real-world studies described the clinicopathological characteristics and treatment of such patients in China. Patients were consecutively collected from Sun Yat-sen University Cancer Center. Chi-square test was applied to explore the relationship between ALK fusion status and metastasis sites. Kaplan-Meier methods and multivariable analyses were used to estimate progression-free survival (PFS)...
April 4, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28373069/interstitial-lung-disease-associated-with-crizotinib-in-patients-with-advanced-non-small-cell-lung-cancer-independent-review-of-four-profile-trials
#18
Ken Y Yoneda, Judith R Scranton, Michael A Cadogan, Vanessa Tassell, Sashi Nadanaciva, Keith D Wilner, Nicholas S Stollenwerk
INTRODUCTION: Interstitial lung disease (ILD) is a rare, but potentially serious, side effect associated with crizotinib, a tyrosine kinase inhibitor for anaplastic lymphoma kinase-positive (ALK(+)) advanced non-small cell lung cancer. Our objective was to determine the incidence and nature of ILD associated with crizotinib in 4 PROFILE trials (ClinicalTrials.gov identifiers, NCT00585195, NCT00932451, NCT00932893, and NCT01154140). MATERIALS AND METHODS: Grade ≥ 3 respiratory adverse events (AEs) and serious AEs (SAEs) and any grade AEs/SAEs reported as pneumonitis, ILD, or radiation pneumonitis in trials PROFILE 1001, PROFILE 1005, PROFILE 1007, and PROFILE 1014 were evaluated by an expert independent review committee that included a pulmonologist, medical oncologist, and radiologist...
March 14, 2017: Clinical Lung Cancer
https://www.readbyqxmd.com/read/28369651/placental-disposition-and-effects-of-crizotinib-an-ex-vivo-study-in-the-isolated-dual-side-perfused-human-cotyledon
#19
Gaby A M Eliesen, Petra van den Broek, Jeroen J van den Heuvel, Albert Bilos, Jeanne Pertijs, Joris van Drongelen, Frans G M Russel, R Greupink
Background: Tyrosine kinase inhibitors (TKIs) play an important role in cancer pharmacotherapy, yet there is limited data on their use during pregnancy. We studied placental disposition and placental toxicity of crizotinib, a TKI used to treat non-small cell lung cancer. Material and methods: Term placentas were perfused for three hours with crizotinib (1µM) using the ex vivo dual-side cotyledon perfusion technique. Interference of TKIs with trophoblast viability was studied using BeWo cells...
March 24, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28369553/ceritinib-in-patients-with-advanced-crizotinib-treated-anaplastic-lymphoma-kinase-rearranged-nsclc-japanese-subset
#20
Toyoaki Hida, Miyako Satouchi, Kazuhiko Nakagawa, Takashi Seto, Shingo Matsumoto, Katsuyuki Kiura, Hiroshi Nokihara, Haruyasu Murakami, Kota Tokushige, Ben Hatano, Makoto Nishio
Introduction: Anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer is sensitive to tyrosine kinase inhibitors; however, resistance can develop. Data are presented from the phase II trial (ASCEND-2) evaluating efficacy and safety in a subset of Japanese patients with ALK-rearranged non-small cell lung cancer previously treated with platinum-based chemotherapy, who experienced disease progression on crizotinib. Methods: Patients with advanced ALK-rearranged non-small cell lung cancer, including those with asymptomatic or neurologically stable baseline brain metastases, received oral ceritinib 750 mg/day...
March 28, 2017: Japanese Journal of Clinical Oncology
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