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https://www.readbyqxmd.com/read/29145561/clinical-significance-of-cd73-in-triple-negative-breast-cancer-multiplex-analysis-of-a-phase-iii-clinical-trial
#1
L Buisseret, S Pommey, B Allard, S Garaud, M Bergeron, I Cousineau, L Ameye, Y Bareche, M Paesmans, J P A Crown, A Di Leo, S Loi, M Piccart-Gebhart, K Willard-Gallo, C Sotiriou, J Stagg
Background: CD73 is an ecto-enzyme that promotes tumor immune escape through the production of immunosuppressive extracellular adenosine in the tumor microenvironment. Several CD73 inhibitors and adenosine receptor antagonists are being evaluated in phase I clinical trials. Patients and methods: Full-face sections from formalin-fixed paraffin-embedded primary breast tumors from 122 samples of triple-negative breast cancer from the BIG 02-98 adjuvant phase III clinical trial were included in our analysis...
November 14, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29145211/patient-reported-outcome-results-from-the-open-label-randomized-phase-iii-select-bc-trial-evaluating-first-line-s-1-therapy-for-metastatic-breast-cancer
#2
Takuya Kawahara, Kojiro Shimozuma, Takeru Shiroiwa, Yasuhiro Hagiwara, Yukari Uemura, Takanori Watanabe, Naruto Taira, Takashi Fukuda, Yasuo Ohashi, Hirofumi Mukai
OBJECTIVE: To evaluate the effects of S-1, an orally administered 5-FU agent, versus taxane on patient-reported outcomes (PROs) in the SELECT BC trial. METHODS: Patients with HER2-negative and endocrine treatment-resistant breast cancer with metastasis or recurrence after surgery were randomly assigned to receive first-line taxane or S-1. PROs (secondary endpoint) were assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) and Patient Neurotoxicity Questionnaire (PNQ) at baseline and at 3, 6, and 12 months...
November 17, 2017: Oncology
https://www.readbyqxmd.com/read/29140138/cox-2-expression-and-effects-of-celecoxib-in-addition-to-standard-chemotherapy-in-advanced-non-small-cell-lung-cancer
#3
Miklos Gulyas, Johanna Sofia Margareta Mattsson, Andrea Lindgren, Lars Ek, Kristina Lamberg Lundström, Annelie Behndig, Erik Holmberg, Patrick Micke, Bengt Bergman
AIM: Inhibition of cyclooxygenase-2 (COX-2) is proposed as a treatment option in several cancer types. However, in non-small cell lung cancer (NSCLC), phase III trials have failed to demonstrate a benefit of adding COX-2 inhibitors to standard chemotherapy. The aim of this study was to analyze COX-2 expression in tumor and stromal cells as predictive biomarker for COX-2 inhibition. METHODS: In a multicenter phase III trial, 316 patients with advanced NSCLC were randomized to receive celecoxib (400 mg b...
November 15, 2017: Acta Oncologica
https://www.readbyqxmd.com/read/29137320/a-phase-ii-study-of-s-1-with-concurrent-radiotherapy-in-elderly-patients-with-esophageal-cancer
#4
Yongling Ji, Xianghui Du, Ye Tian, Liming Sheng, Lei Cheng, Ying Chen, Guoqing Qiu, Xia Zhou, Wuan Bao, Danhong Zhang, Ming Chen
Background: Concurrent chemoradiotherapy (CCRT) using conventional platinum-based doublets are often associated with significant incidence of toxic effects in elderly patients with esophageal cancer. We previously reported a phase I trial of CCRT using S-1, an oral 5-fluorouracil derivative, which yielded well safe and active outcomes. Methods: Patients with histologically confirmed esophageal cancer, who were age of 70 years or older with performance status (PS) score of 0-2 or age of 66 to 69 with PS score of 2, were eligible for this Phase II trial...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29136387/randomized-multicenter-placebo-controlled-clinical-trial-of-duloxetine-versus-placebo-for-aromatase-inhibitor-associated-arthralgias-in-early-stage-breast-cancer-swog-s1202
#5
N Lynn Henry, Joseph M Unger, Anne F Schott, Louis Fehrenbacher, Patrick J Flynn, Debra M Prow, Carl W Sharer, Gary V Burton, Charles S Kuzma, Anna Moseley, Danika L Lew, Michael J Fisch, Carol M Moinpour, Dawn L Hershman, James L Wade
Purpose Adherence to aromatase inhibitor (AI) therapy for early-stage breast cancer is limited by AI-associated musculoskeletal symptoms (AIMSS). Duloxetine is US Food and Drug Administration approved for treatment of multiple chronic pain disorders. We hypothesized that treatment of AIMSS with duloxetine would improve average joint pain compared with placebo. Methods This randomized, double-blind, phase III trial included AI-treated postmenopausal women with early-stage breast cancer and who had average joint pain score of ≥ 4 out of 10 that developed or worsened since AI therapy initiation...
November 14, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/29134432/phase-iii-study-of-dulanermin-recombinant-human-tumor-necrosis-factor-related-apoptosis-inducing-ligand-apo2-ligand-combined-with-vinorelbine-and-cisplatin-in-patients-with-advanced-non-small-cell-lung-cancer
#6
Xuenong Ouyang, Meiqi Shi, Fangwei Jie, Yuxian Bai, Peng Shen, Zhuang Yu, Xiuwen Wang, Cheng Huang, Min Tao, Zhehai Wang, Conghua Xie, Qi Wu, Yongqian Shu, Baohui Han, Fengchun Zhang, Yiping Zhang, Chunhong Hu, Xitao Ma, Yongjie Liang, Anlan Wang, Bing Lu, Yi Shi, Jinfei Chen, Zhixiang Zhuang, Jiejun Wang, Jianjin Huang, Changhui Wang, Chunxue Bai, Xin Zhou, Qiang Li, Feng Chen, Hao Yu, Jifeng Feng
Background Dulanermin is a recombinant soluble human Apo2 ligand/tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) that activates apoptotic pathways by binding to proapoptotic death receptor (DR) 4 and DR5. The purpose of this study was to evaluate the efficacy and safety of dulanermin combined with vinorelbine and cisplatin (NP) as the first-line treatment for patients with advanced non-small-cell lung cancer (NSCLC). Experimental design Patients were randomly assigned to receive NP chemotherapy (vinorelbine 25 mg/m(2) on days 1 and 8 and cisplatin 30 mg/m(2) on days 2 to 4) for up to six cycles plus dulanermin (75 μg/kg on days 1 to 14) or placebo every three weeks until disease progression, intolerable toxicity, or withdrawal of consent...
November 14, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/29133080/population-pharmacokinetics-of-nintedanib-in-patients-with-idiopathic-pulmonary-fibrosis
#7
Ulrike Schmid, Christiane Doege, Claudia Dallinger, Matthias Freiwald
BACKGROUND: Nintedanib is a potent intracellular inhibitor of tyrosine kinases, including the receptor kinases vascular endothelial growth factor, platelet-derived growth factor and fibroblast growth factor. A previous model assessed the population pharmacokinetics of nintedanib and its main metabolite BIBF 1202 in patients with non-small cell lung cancer and idiopathic pulmonary fibrosis (IPF). The objective of this analysis was to further characterise the population pharmacokinetics of nintedanib in patients with IPF by including data from the Phase III trials...
November 10, 2017: Pulmonary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29132393/interferon-%C3%AE-inducible-protein-16-ifi16-is-required-for-the-maintenance-of-epstein-barr-virus-latency
#8
Gina Pisano, Arunava Roy, Mairaj Ahmed Ansari, Binod Kumar, Leela Chikoti, Bala Chandran
BACKGROUND: Epstein-Barr virus (EBV) exhibits both lytic and latent (Lat. I, II, and III) phases in an infected individual. It's during the latent phase of EBV that all EBV-associated cancers, including Burkitt's lymphoma, nasopharyngeal carcinoma and lymphoproliferative disease arise. Interferon-γ-inducible protein 16 (IFI16) is a well-established innate immune sensor and viral transcriptional regulator involved in response to invading DNA viruses. During latency, IFI16 remains in the nucleus, in part bound to the EBV genome; however, neither its role in EBV lytic cycle or latency has been established...
November 13, 2017: Virology Journal
https://www.readbyqxmd.com/read/29130344/neurokinin-1-receptor-antagonists-in-the-prevention-of-chemotherapy-induced-nausea-and-vomiting-focus-on-fosaprepitant
#9
Bernardo L Rapoport, Karin Jordan, Cindy Weinstein
Chemotherapy-induced nausea and vomiting (CINV) remains a challenge in cancer care. Improved understanding of CINV pathophysiology has triggered the development of new antiemetic therapeutic options, such as selective neurokinin-1 (NK1) receptor antagonists (RAs), which effectively prevent CINV when added to a standard antiemetic regimen (serotonin-3 RA and dexamethasone). Aprepitant and its water-soluble prodrug, fosaprepitant dimeglumine, are the most widely used NK1 RAs, with extensive clinical use worldwide...
November 13, 2017: Future Oncology
https://www.readbyqxmd.com/read/29129758/impact-of-nivolumab-versus-docetaxel-on-health-related-quality-of-life-and-symptoms-in-patients-with-advanced-squamous-non-small-cell-lung-cancer-results-from-the-checkmate-017-study
#10
Martin Reck, Fiona Taylor, John R Penrod, Michael DeRosa, Laura Morrissey, Homa Dastani, Lucinda Orsini, Richard J Gralla
INTRODUCTION: In the phase III CheckMate 017 study, nivolumab prolonged overall survival versus docetaxel in previously treated patients with advanced squamous non-small cell lung cancer (NSCLC). Study objectives included health-related quality of life (HRQoL) and symptom assessments. METHODS: Patients serially completed Lung Cancer Symptom Scale (LCSS) and European Quality of Life Five Dimensions (EQ-5D) questionnaires. The LCSS average symptom burden index (ASBI; mean score for six lung cancer-specific symptoms; range, 0-100), LCSS 3-item global index, EQ-5D utility index, and EQ-5D visual analog scale scores were analyzed...
November 9, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/29129089/systemic-therapy-for-esophageal-cancer-chemotherapy
#11
Geoffrey Y Ku
As one-half of patients with esophagogastric cancer (EGC) present with metastatic disease and the majority of patients with locally advanced disease will eventually develop metastatic disease despite multimodality therapy, most patients will receive palliative chemotherapy at some point. The reference first-line regimen consists of a fluoropyrimidine/platinum combination, which is the standard in East Asia, where this disease is endemic. Options include infusional 5-fluorouracil (5-FU), capecitabine, S-1 and other oral 5-FU pro-drugs and cisplatin or oxaliplatin...
October 2017: Chinese Clinical Oncology
https://www.readbyqxmd.com/read/29129088/systemic-therapy-for-esophagogastric-cancer-targeted-therapies
#12
Tomas G Lyons, Geoffrey Y Ku
The poor prognosis for patients with esophagogastric cancers (EGC) has resulted in an increased focus on the use of targeted agents in this disease. Targets include epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), Her2, mammalian target of rapamycin (mTOR), MET, poly (ADP-ribose) polymerase (PARP) and claudin 18.2 (CLDN18.2). Trastuzumab, an anti-Her2 antibody, was approved by the U.S. FDA in 2010 as first-line therapy in combination with chemotherapy for Her2-positive disease...
October 2017: Chinese Clinical Oncology
https://www.readbyqxmd.com/read/29127587/copanlisib-first-global-approval
#13
Anthony Markham
Bayer are developing copanlisib (Aliqopa™)-a pan-class I phosphoinositide 3-kinase (PI3K) inhibitor-as a treatment for various haematological and solid malignancies. The US FDA has granted copanlisib accelerated approval for the treatment of adults with relapsed follicular lymphoma who have received at least two prior systemic therapies based on the results of a phase II trial. Phase III trials are underway evaluating copanlisib as treatment for relapsed/refractory diffuse large B-cell lymphoma and in combination with rituximab or rituximab-based chemotherapy or standard immunochemotherapy in patients with relapsed indolent B-cell non-Hodgkin's lymphoma...
November 10, 2017: Drugs
https://www.readbyqxmd.com/read/29126091/older-cancer-patients-in-cancer-clinical-trials-are-underrepresented-systematic-literature-review-of-almost-5000-meta-and-pooled-analyses-of-phase-iii-randomized-trials-of-survival-from-breast-prostate-and-lung-cancer
#14
REVIEW
Cita Dunn, Andrew Wilson, Freddy Sitas
BACKGROUND: Older people represent increasing proportions of the population with cancer. To understand the representivity of cancer treatments in older people, we performed a systematic literature review using PRISMA guidelines of the age distribution of clinical trial participants for three leading cancer types, namely breast, prostate, and lung. METHODS: We used PubMed to identify articles detailing meta or pooled-analyses of phase III, randomised controlled trials (RCTs) of survival for breast, prostate and lung cancer, published ≤5 years from 2016...
November 7, 2017: Cancer Epidemiology
https://www.readbyqxmd.com/read/29123260/combining-dna-damaging-therapeutics-with-immunotherapy-more-haste-less-speed
#15
REVIEW
Jessica S Brown, Raghav Sundar, Juanita Lopez
The idea that chemotherapy can be used in combination with immunotherapy may seem somewhat counterproductive, as it can theoretically eliminate the immune cells needed for antitumour immunity. However, much preclinical work has now demonstrated that in addition to direct cytotoxic effects on cancer cells, a proportion of DNA damaging agents may actually promote immunogenic cell death, alter the inflammatory milieu of the tumour microenvironment and/or stimulate neoantigen production, thereby activating an antitumour immune response...
November 9, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/29121501/does-c-met-remain-a-rational-target-for-therapy-in-patients-with-egfr-tki-resistant-non-small-cell-lung-cancer
#16
REVIEW
Yi-Long Wu, Ross Andrew Soo, Giuseppe Locatelli, Uz Stammberger, Giorgio Scagliotti, Keunchil Park
Non-small cell lung cancer (NSCLC) inevitably develops resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) treatment. In 5-20% of cases, this can be attributed to aberrant c-Met activity, providing a clear rationale for the use of c-Met inhibitors in these patients. EGFR TKI-resistant tumors often remain sensitive to EGFR signaling, such that c-Met inhibitors are likely to be most effective when combined with continued EGFR TKI therapy. The phase III trials of the c-Met inhibitors onartuzumab and tivantinib, which failed to demonstrate significant benefit in patients with NSCLC but excluded patients with EGFR TKI-resistant disease, do not allow c-Met to be dismissed as a rational target in EGFR TKI-resistant NSCLC...
October 25, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/29120911/immunotherapy-for-kidney-cancer-status-quo-and-the-future
#17
Jens Bedke, Viktoria Stühler, Arnulf Stenzl, Bernhard Brehmer
PURPOSE OF REVIEW: The treatment landscape in advanced and metastatic renal cell carcinoma (RCC) is moving from the inhibition of tyrosine kinases (TKI) and the mammalian target of rapamycin (mTOR) inhibitors to specific immunooncology agents like immune checkpoint inhibitors (ICI). The review focus on the recent immunooncology developments and available trial results within the last 12 months. RECENT FINDINGS: ICI as monotherapy (nivolumab) or immunooncology and immunooncology combinations (nivolumab and ipilimumab) demonstrated positive results on prolonged overall survival in phase III trials...
November 7, 2017: Current Opinion in Urology
https://www.readbyqxmd.com/read/29119354/characteristics-and-outcomes-of-breast-cancer-patients-enrolled-in-the-national-cancer-institute-cancer-therapy-evaluation-program-sponsored-phase-i-clinical-trials
#18
Filipa Lynce, Matthew J Blackburn, Ling Cai, Heping Wang, Larry Rubinstein, Pamela Harris, Claudine Isaacs, Paula R Pohlmann
PURPOSE: Breast cancer (BC) is the most commonly diagnosed cancer and the second leading cause of cancer-related death among women. Given the availability of approved therapies and abundance of phase II and III clinical trials, historically few BC patients have been referred for consideration of participation on a phase I trial. We were interested in determining whether clinical benefit rates differed in patients with BC from other patients enrolled in phase I trials. METHODS: We performed a retrospective analysis of all Cancer Therapy Evaluation Program (CTEP) sponsored phase I trials from 1993 to 2012...
November 8, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/29119292/population-pharmacokinetics-of-nintedanib-an-inhibitor-of-tyrosine-kinases-in-patients-with-non-small-cell-lung-cancer-or-idiopathic-pulmonary-fibrosis
#19
Ulrike Schmid, Karl-Heinz Liesenfeld, Angele Fleury, Claudia Dallinger, Matthias Freiwald
PURPOSE: A population pharmacokinetic model was developed for nintedanib in patients with non-small cell lung cancer (NSCLC) or idiopathic pulmonary fibrosis (IPF). The effects of intrinsic and extrinsic patient factors on exposure of nintedanib and its main metabolite BIBF 1202 were studied. METHODS: Data from 1191 patients with NSCLC (n = 849) or IPF (n = 342) treated with oral nintedanib (once- or twice-daily, dose range 50-250 mg) in 4 Phase II or III studies were combined...
November 8, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/29118265/a-systematic-review-of-health-related-quality-of-life-reporting-in-ovarian-cancer-phase-iii-clinical-trials-room-to-improve
#20
REVIEW
Michelle K Wilson, Michael L Friedlander, Florence Joly, Amit M Oza
BACKGROUND: Epithelial ovarian cancer (OC) remains a significant cause of morbidity and mortality for women worldwide. Patients may experience a multitude of disease- and treatment-related symptoms that can impact quality of life (QOL) and should be measured and reported in clinical trials. This systematic review investigated the adequacy of reporting of QOL in randomized phase III trials in OC in both the first-line and recurrent disease setting. MATERIALS AND METHODS: A systematic review of MEDLINE and EMBASE identified randomized clinical trials of systemic therapy in OC from 1980 to 2014...
November 8, 2017: Oncologist
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