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Nsclc clinical trials

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https://www.readbyqxmd.com/read/28525370/mathematical-modelling-for-phase-i-cancer-trials-a-study-of-metronomic-vinorelbine-for-advanced-non-small-cell-lung-cancer-nsclc-and-mesothelioma-patients
#1
Fabrice Barlesi, Diane-Charlotte Imbs, Pascale Tomasini, Laurent Greillier, Melissa Galloux, Albane Testot-Ferry, Mélanie Garcia, Xavier Elharrar, Annick Pelletier, Nicolas André, Céline Mascaux, Bruno Lacarelle, Raouf El Cheikh, Raphaël Serre, Joseph Ciccolini, Dominique Barbolosi
INTRODUCTION: Using mathematical modelling allows to select a treatment's regimen across infinite possibilities. Here, we report the phase I assessment of a new schedule for metronomic vinorelbine in treating refractory advanced NSCLC and mesothelioma patients. RESULTS: Overall, 13 patients were screened and 12 were treated (50% male, median age: 68yrs), including 9 NSCLC patients. All patients received at least one week (3 doses) of treatment. At data cut-off, the median length of treatment was 6...
May 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28522754/met-exon-14-mutation-encodes-an-actionable-therapeutic-target-in-lung-adenocarcinoma
#2
Xinyuan Lu, Nir Peled, John Greer, Wei Wu, Peter Choi, Alice H Berger, Sergio Wong, Kuang-Yu Jen, Youngho Seo, Byron Hann, Angela Brooks, Matthew Meyerson, Eric A Collisson
Targeting somatically activated oncogenes has revolutionized the treatment of non-small cell lung cancer (NSCLC). Mutations in the gene mesenchymal-epithelial transition (MET) near the exon 14 splice sites are recurrent in lung adenocarcinoma and cause exon skipping (METΔ14). Here we analyzed 4,422 samples from 12 different malignancies to estimate the rate of said exon skipping. METΔ14 mutation and transcript were most common in lung adenocarcinoma. Endogenously expressed levels of METΔ14 transformed human epithelial lung cells in a Hepatocyte growth factor (HGF)-dependent manner...
May 18, 2017: Cancer Research
https://www.readbyqxmd.com/read/28521435/a-prospective-cohort-study-of-patients-with-non-squamous-non-small-cell-lung-cancer-treated-with-bevacizumab
#3
Katsuhiko Naoki, Yuichiro Takeda, Kenzo Soejima, Daisuke Arai, Go Naka, Seisuke Nagase, Ken Arimura, Toshinori Kanemura, Tatsuo Ohhira, Norihiko Ikeda
First-line chemotherapy regimens that include bevacizumab (Bev) have been hypothesized to improve outcomes in patients with advanced non-squamous non-small cell lung cancer (non-sq NSCLC). Although approved to treat NSCLC in 2009, insufficient data exist on the clinical uses of Bev in Japan. The present study prospectively evaluated the efficacy and safety of Bev-containing combination chemotherapy. Eligible patients exhibited histologically or cytologically documented advanced or recurrent non-sq NSCLC. Patients were administered 15 mg/kg Bev with standard chemotherapy followed by maintenance Bev...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28515943/evaluation-of-dosing-strategy-for-pembrolizumab-for-oncology-indications
#4
Tomoko Freshwater, Anna Kondic, Malidi Ahamadi, Claire H Li, Rik de Greef, Dinesh de Alwis, Julie A Stone
BACKGROUND: Traditionally, most monoclonal antibodies (mAbs) have been dosed based on body weight because of perceived contribution of body size in pharmacokinetic variability. The same approach was used in the initial pembrolizumab studies; however, following availability of PK data, the need for weight-based dosing for pembrolizumab was reassessed. METHODS: A previously established population PK (popPK) model as well as exposure-response results from patients with advanced melanoma or non-small cell lung cancer (NSCLC) were used to evaluate the potential application of a fixed dosing regimen with the aim of maintaining pembrolizumab exposures within the range demonstrated to provide near maximal efficacy and acceptable safety...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28515940/nivolumab-induced-autoimmune-diabetes-mellitus-presenting-as-diabetic-ketoacidosis-in-a-patient-with-metastatic-lung-cancer
#5
James Luke Godwin, Shuchie Jaggi, Imali Sirisena, Pankaj Sharda, Ajay D Rao, Ranee Mehra, Colleen Veloski
BACKGROUND: Advances in cancer immunotherapy have generated encouraging results in multiple malignancies refractory to standard chemotherapies. As the use of immune checkpoint inhibitors (ICI) proliferates, the incidence of autoimmune side effects associated with these agents, termed immune related adverse events (irAE), is expected to increase. The frequency of significant irAE in ICI treated patients is about 10-20% and early recognition is critical to prevent serious morbidity and even mortality...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28513466/non-small-cell-lung-cancer-mutations-targeted-and-combination-therapy
#6
Justyna Kutkowska, Irena Porębska, Andrzej Rapak
Year after year, a growing number of cases of non-small cell lung cancer (NSCLC), mostly caused by smoking, have been noted. Most patients die because of the late detection of cancer and tumor resistance to treatment with cytostatics. Treatment of patients with advanced NSCLC is impeded by the low sensitivity of the tumor to cytostatic agents and the co-existence of many diseases, which substrate is, like lung cancer, cigarette smoking. Along with the development of molecular biology, targeted therapy has started to be used, affecting specific signaling pathways involved in the processes of oncogenesis...
May 17, 2017: Postȩpy Higieny i Medycyny Doświadczalnej
https://www.readbyqxmd.com/read/28512260/targeting-metabolism-and-amp-activated-kinase-with-metformin-to-sensitize-non-small-cell-lung-cancer-nsclc-to-cytotoxic-therapy-translational-biology-and-rationale-for-current-clinical-trials
#7
REVIEW
Michael Troncone, Stephanie M Cargnelli, Linda A Villani, Naghmeh Isfahanian, Lindsay A Broadfield, Laura Zychla, Jim Wright, Gregory Pond, Gregory R Steinberg, Theodoros Tsakiridis
Lung cancer is the most fatal malignancy worldwide, in part, due to high resistance to cytotoxic therapy. There is need for effective chemo-radio-sensitizers in lung cancer. In recent years, we began to understand the modulation of metabolism in cancer and its importance in tumor progression and survival after cytotoxic therapy. The activity of biosynthetic pathways, driven by the Growth Factor Receptor/Ras/PI3k/Akt/mTOR pathway, is balanced by the energy stress sensor pathway of LKB1/AMPK/p53. AMPK responds both to metabolic and genotoxic stress...
April 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28508945/clinical-efficacy-of-percutaneous-cryoablation-combined-with-allogenic-nk-cell-immunotherapy-for-advanced-non-small-cell-lung-cancer
#8
Mao Lin, Shu-Zhen Liang, Xiao-Hua Wang, Ying-Qing Liang, Ming-Jie Zhang, Li-Zhi Niu, Ji-Bing Chen, Hai-Bo Li, Ke-Cheng Xu
In this study, the safety and clinical efficacy of cryosurgery combined with allogenic NK cell immunotherapy for the treatment of advanced non-small cell lung cancer (NSCLC) were evaluated. From July 2016 to March 2017, we enrolled 60 patients who met the enrollment criteria and divided them into two groups: (1) the simple cryoablation group (n = 30) and (2) the cryoablation combined with allogenic NK cell group (n = 30). The changes in immune function, quality of life, and clinical response were evaluated...
May 16, 2017: Immunologic Research
https://www.readbyqxmd.com/read/28507206/real-world-data-on-prognostic-factors-for-overall-survival-in-egfr-mutation-positive-advanced-non-small-cell-lung-cancer-patients-treated-with-first-line-gefitinib
#9
Zong-Han Yao, Wei-Yu Liao, Chao-Chi Ho, Kuan-Yu Chen, Jin-Yuan Shih, Jin-Shing Chen, Zhong-Zhe Lin, Chia-Chi Lin, James Chih-Hsin Yang, Chong-Jen Yu
BACKGROUND: This study aimed to identify independent prognostic factors for overall survival (OS) of patients with advanced non-small cell lung cancer (NSCLC) harboring an activating epidermal growth factor receptor (EGFR) mutation and receiving gefitinib as first-line treatment in real-world practice. MATERIALS AND METHODS: We enrolled 226 patients from June 2011 to May 2013. During this period, gefitinib was the only EGFR-tyrosine kinase inhibitor reimbursed by the Bureau of National Health Insurance of Taiwan...
May 15, 2017: Oncologist
https://www.readbyqxmd.com/read/28502785/car-t-cell-therapy-for-lung-cancer-and-malignant-pleural-mesothelioma
#10
REVIEW
Masha Zeltsman, Jordan Dozier, Erin McGee, Daniel Ngai, Prasad S Adusumilli
Immunotherapy is a promising field that harnesses the power of the immune system as a therapeutic agent for cancer treatment. Beneficial outcomes shown in patients with non-small cell lung cancer (NSCLC) and malignant pleural mesothelioma (MPM) with relatively higher tumor-infiltrating T cells, combined with impressive responses obtained in a cohort of patients with NSCLC following checkpoint blockade therapy, lays a strong foundation to promote effector immune responses in these patients. One such approach being investigated is administration of tumor antigen-targeted T cells with transduction of a chimeric antigen receptor (CAR)...
April 26, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28499641/outcomes-of-research-biopsies-in-clinical-trials-of-egfr-mutation-positive-non-small-cell-lung-cancer-patients-pretreated-with-egfr-tyrosine-kinase-inhibitors
#11
Bin-Chi Liao, Ya-Ying Bai, Jih-Hsiang Lee, Chia-Chi Lin, Shu-Yung Lin, Yee-Fan Lee, Chao-Chi Ho, Jin-Yuan Shih, Yeun-Chung Chang, Chong-Jen Yu, James Chih-Hsin Yang, Pan-Chyr Yang
BACKGROUND/PURPOSE: Research biopsies (RBs) are crucial for developing novel molecular targeted agents. However, the safety and diagnostic yields of RBs have not been investigated in EGFR mutation-positive non-small cell lung cancer (NSCLC) patients pretreated with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). METHODS: We searched the medical records of NSCLC patients who participated in lung cancer clinical trials and underwent mandatory RBs between 2012 and 2014 at our institution...
May 9, 2017: Journal of the Formosan Medical Association, Taiwan Yi Zhi
https://www.readbyqxmd.com/read/28499515/incidence-of-pneumonitis-with-use-of-pd-1-and-pd-l1-inhibitors-in-non-small-cell-lung-cancer-a-systematic-review-and-meta-analysis-of-trials
#12
Monica Khunger, Sagar Rakshit, Vinay Pasupuleti, Adrian V Hernandez, Peter Mazzone, James Stevenson, Nathan A Pennell, Vamsidhar Velcheti
BACKGROUND: PD-1/PD-L1 inhibitors show significant clinical activity in non-small cell lung carcinoma (NSCLC). However, they are often associated with potentially fatal immune mediated pneumonitis. Preliminary reports of trials suggest a difference in the rate of pneumonitis with PD-1 and PD-L1 inhibitors. We sought to determine the overall incidence of pneumonitis, and differences according to type of inhibitors and prior chemotherapy use. METHODS: Medline, Embase and Scopus databases were searched up to November 2016...
May 9, 2017: Chest
https://www.readbyqxmd.com/read/28495513/high-hydrostatic-pressure-affects-antigenic-pool-in-tumor-cells-implication-for-dendritic-cell-based-cancer-immunotherapy
#13
Linda Urbanova, Nada Hradilova, Irena Moserova, Sarka Vosahlikova, Lenka Sadilkova, Michal Hensler, Radek Spisek, Irena Adkins
High hydrostatic pressure (HHP) can be used to generate dendritic cell (DC)-based active immunotherapy for prostate, lung and ovarian cancer. We showed here that HHP treatment of selected human cancer cell lines leads to a degradation of tumor antigens which depends on the magnitude of HHP applied and on the cancer cell line origin. Whereas prostate or ovarian cell lines displayed little protein antigen degradation with HHP treatment up to 300MPa after 2h, tumor antigens are hardly detected in lung cancer cell line after treatment with HHP 250MPa at the same time...
May 8, 2017: Immunology Letters
https://www.readbyqxmd.com/read/28492898/selumetinib-plus-docetaxel-compared-with-docetaxel-alone-and-progression-free-survival-in-patients-with-kras-mutant-advanced-non-small-cell-lung-cancer-the-select-1-randomized-clinical-trial
#14
Pasi A Jänne, Michel M van den Heuvel, Fabrice Barlesi, Manuel Cobo, Julien Mazieres, Lucio Crinò, Sergey Orlov, Fiona Blackhall, Juergen Wolf, Pilar Garrido, Artem Poltoratskiy, Gabriella Mariani, Dana Ghiorghiu, Elaine Kilgour, Paul Smith, Alexander Kohlmann, David J Carlile, David Lawrence, Karin Bowen, Johan Vansteenkiste
Importance: There are no specifically approved targeted therapies for the most common genomically defined subset of non-small cell lung cancer (NSCLC), KRAS-mutant lung cancer. Objective: To compare efficacy of the mitogen-activated protein kinase kinase (MEK) inhibitor selumetinib + docetaxel with docetaxel alone as a second-line therapy for advanced KRAS-mutant NSCLC. Design, Setting, and Participants: Multinational, randomized clinical trial conducted at 202 sites across 25 countries from October 2013 through January 2016...
May 9, 2017: JAMA: the Journal of the American Medical Association
https://www.readbyqxmd.com/read/28492290/atezolizumab-a-novel-pd-l1-inhibitor-in-cancer-therapy-with-a-focus-in-bladder-and-non-small-cell-lung-cancers
#15
A Krishnamurthy, A Jimeno
In recent years, immunotherapy has come to the forefront as a major development in cancer treatment. Evasion of the immune system by tumor cells has been identified as one of the hallmarks of cancer and multiple therapies have been developed to counter this process. Programmed cell death 1 ligand 1 (PD-L1), a ligand to programmed cell death protein 1 (PD-1), is expressed by many cancer cells and the binding of PD-L1 to PD-1 results in the suppression of T-cell-mediated immune response against cancer cells. Atezolizumab is a monoclonal antibody that binds to PD-L1 and blocks its interaction with PD-1, thereby enhancing T-cell activity against tumor cells...
April 2017: Drugs of Today
https://www.readbyqxmd.com/read/28490925/management-of-egfr-mutated-non-small-cell-lung-cancer-practical-implications-from-a-clinical-and-pathology-perspective
#16
REVIEW
M Cabanero, R Sangha, B S Sheffield, M Sukhai, M Pakkal, S Kamel-Reid, A Karsan, D Ionescu, R A Juergens, C Butts, M S Tsao
Starting in the early 2000s, non-small-cell lung cancer (nsclc) subtypes have evolved from being histologically described to molecularly defined. Management of lung adenocarcinomas now generally requires multiple molecular tests at baseline to define the optimal treatment strategy. More recently, second biopsies performed at progression in patients treated with tyrosine kinase inhibitors (tkis) have further defined the continued use of molecularly targeted therapy. In the present article, we focus on one molecular subtype: EGFR-mutated nsclc...
April 2017: Current Oncology
https://www.readbyqxmd.com/read/28489511/phase-iii-randomized-placebo-controlled-double-blind-trial-of-celecoxib-in-addition-to-standard-chemotherapy-for-advanced-non-small-cell-lung-cancer-with-cyclooxygenase-2-overexpression-calgb-30801-alliance
#17
Martin J Edelman, Xiaofei Wang, Lydia Hodgson, Richard T Cheney, Maria Q Baggstrom, Sachdev P Thomas, Ajeet Gajra, Erin Bertino, Karen L Reckamp, Julian Molina, Joan H Schiller, Kisha Mitchell-Richards, Paula N Friedman, Jon Ritter, Ginger Milne, Olwen M Hahn, Thomas E Stinchcombe, Everett E Vokes
Purpose Tumor overexpression of cyclooxygenase-2 (COX-2) has been associated with worse outcome in non-small-cell lung cancer (NSCLC). In Cancer and Leukemia Group B (CALGB) 30203, we found that the selective COX-2 inhibitor celecoxib in addition to chemotherapy in advanced NSCLC improved progression-free and overall survival in patients with moderate to high COX-2 expression by immunohistochemistry (IHC). CALGB 30801 (Alliance) was designed to prospectively confirm that finding. Patients and Methods Patients with NSCLC (stage IIIB with pleural effusion or stage IV according to American Joint Committee on Cancer [sixth edition] criteria) were preregistered, and biopsy specimens were analyzed for COX-2 by IHC...
May 10, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28484235/extent-of-visceral-pleural-invasion-affects-prognosis-of-resected-non-small-cell-lung-cancer-a-meta-analysis
#18
Ting Wang, Chengya Zhou, Qinghua Zhou
Visceral pleural invasion (VPI) has been known to be an adverse prognostic factor in non-small cell lung cancer (NSCLC). However, the prognostic significance of extent of VPI (PL0, PL1 and PL2) remains controversial. We conduct a meta-analysis to summarize available evidence on this topic. PubMed, EMBASE, OVID and The Cochrane Library were searched for published studies from inception to May 9, 2016. A total of 16 studies were included in meta-analysis. Our results showed that patients with PL1 or PL2 had poorer overall survival compared with PL0 (HR = 1...
May 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28482670/immune-checkpoint-inhibitors-in-lung-cancer-current-status-and-future-directions
#19
Yun Fan, Weimin Mao
Recently, the immune checkpoint inhibitors that target programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) have made a breakthrough in treating advanced non-small cell lung cancer (NSCLC) with the efficacy of approximately 20%; among which, nivolumab has acquired treatment indications in lung squamous cell carcinoma. The inhibitors targeting cytotoxic T lymphocyte associated antigen 4 (CTLA-4) are also undergoing clinical trials. Researches on immune checkpoint inhibitors have been rapidly implemented in a variety of different types of lung cancer, such as small cell lung cancer (SCLC) and locally advanced NSCLC, and these inhibitors began to be applied in combination with some established treatments, including chemotherapy, targeting therapy and radiotherapy...
April 2017: Chinese Clinical Oncology
https://www.readbyqxmd.com/read/28479369/genomic-profiling-of-advanced-non-small-cell-lung-cancer-in-community-settings-gaps-and-opportunities
#20
Martin E Gutierrez, Kelly Choi, Richard B Lanman, Edward J Licitra, Stanley M Skrzypczak, Ruth Pe Benito, Tommy Wu, Srikesh Arunajadai, Sukhi Kaur, Harry Harper, Andrew L Pecora, Eric V Schultz, Stuart L Goldberg
BACKGROUND: National guidelines have advocated broad molecular profiling as a part of the standard diagnostic evaluation for advanced non-small cell lung cancer (NSCLC), with the goal of identifying driver mutations for which effective therapies or clinical trials are available. However, adherence to genomic testing guidelines could present challenges to community oncologists. PATIENTS AND METHODS: We performed a retrospective review of genomic testing patterns in patients with nonsquamous NSCLC treated by 89 oncologists at 15 sites throughout New Jersey and Maryland from January 2013 to December 2015...
April 13, 2017: Clinical Lung Cancer
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