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https://www.readbyqxmd.com/read/29143328/efficacy-and-safety-of-anti-egfr-agents-administered-concurrently-with-standard-therapies-for-patients-with-head-and-neck-squamous-cell-carcinoma-a-systematic-review-and-meta-analysis-of-randomized-controlled-trials
#1
REVIEW
Tian Yunhong, Lin Jie, Tian Yunming, Zhang Guoqian, Zeng Xing, Zheng Ronghui, Zhang Weijun, Yuan Yawei
Agents targeting epidermal growth factor receptor (EGFR) are used to treat head and neck squamous cell carcinoma (HNSCC); however, their efficacy and safety is poorly understood. Here we evaluated the efficacy and safety of anti-EGFR agents administered concurrently with standard therapies for HNSCC. Randomized controlled trials that evaluated addition of EGFR targeted therapy versus standard therapy alone were included. The primary outcome was overall survival (OS). Secondary outcomes were progression-free survival (PFS), overall response rate (ORR), locoregional control, and severe adverse events (SAEs, grade ≥ 3)...
November 16, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29142750/evaluation-of-epidermal-growth-factor-receptor-serum-levels-and-their-association-with-clinicopathological-characteristics-in-patients-with-colorectal-cancer
#2
Mehmet Karabulut, Cigdem Usul Afsar, Halil Alıs, Ebru Oran, Senem Karabulut, Cevher Akarsu, Nuri Alper Sahbaz, Alpen Yahya Gümüsoglu, Elif Bilgin, Nuri Faruk Aykan
Colorectal cancer (CRC) is a major public health concern and one of the leading causes of cancer-related mortality worldwide. The aim of the present study was to determine the serum epidermal growth factor receptor (sEGFR) levels in healthy volunteers and patients with CRC, to determine the association between tumor marker levels and clinicopathological findings, and investigate its prognostic value. A total of 140 patients with CRC were enrolled in the present study. Pre-treatment sEGFR levels were determined using ELISA...
November 2017: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/29141884/a-method-of-high-throughput-functional-evaluation-of-egfr-gene-variants-of-unknown-significance-in-cancer
#3
Shinji Kohsaka, Masaaki Nagano, Toshihide Ueno, Yoshiyuki Suehara, Takuo Hayashi, Naoko Shimada, Kazuhisa Takahashi, Kenji Suzuki, Kazuya Takamochi, Fumiyuki Takahashi, Hiroyuki Mano
Numerous variants of unknown significance (VUS) have been identified through large-scale cancer genome projects, although their functional relevance remains uninvestigated. We developed a mixed-all-nominated-mutants-in-one (MANO) method to evaluate the transforming potential and drug sensitivity of oncogene VUS in a high-throughput manner and applied this method to 101 nonsynonymous epidermal growth factor receptor (EGFR) mutants. We discovered a number of mutations conferring resistance to EGFR tyrosine kinase inhibitors (TKIs), including gefitinib- and erlotinib-insensitive missense mutations within exon 19 and other gefitinib-resistant mutations, such as L833V, A839T, V851I, A871T, and G873E...
November 15, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/29137335/inhibition-of-cell-cycle-progression-by-the-hydroxytyrosol-cetuximab-combination-yields-enhanced-chemotherapeutic-efficacy-in-colon-cancer-cells
#4
Erika Terzuoli, Ginevra Nannelli, Maria Frosini, Antonio Giachetti, Marina Ziche, Sandra Donnini
Hydroxytyrosol (HT), a polyphenol of olive oil, downregulates epidermal growth factor (EGFR) expression and inhibits cell proliferation in colon cancer (CC) cells, with mechanisms similar to that activated by the EGFR inhibitor, cetuximab. Here, we studied whether HT treatment would enhance the cetuximab inhibitory effects on cell growth in CC cells. HT-cetuximab combination showed greater efficacy in reducing cell growth in HT-29 and WiDr cells at concentrations 10 times lower than when used as single agents...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29137301/antitumor-efficacy-of-triple-monoclonal-antibody-inhibition-of-epidermal-growth-factor-receptor-egfr-with-mm151-in-egfr-dependent-and-in-cetuximab-resistant-human-colorectal-cancer-cells
#5
Stefania Napolitano, Giulia Martini, Erika Martinelli, Carminia Maria Della Corte, Floriana Morgillo, Valentina Belli, Claudia Cardone, Nunzia Matrone, Fortunato Ciardiello, Teresa Troiani
Purpose: We investigated the effect of triple monoclonal antibody inhibition of EGFR to overcome acquired resistance to first generation of anti-EGFR inhibitors. Experimental design: MM151 is a mixture of three different monoclonal IgG1 antibodies directed toward three different, non-overlapping, epitopes of the EGFR. We performed an in vivo study by using human CRC cell lines (SW48, LIM 1215 and CACO2) which are sensitive to EGFR inhibitors, in order to evaluate the activity of MM151 as compared to standard anti-EGFR mAbs, such as cetuximab, as single agent or in a sequential strategy of combination MM151 with irinotecan (induction therapy) followed by MM151 with a selective MEK1/2 inhibitor (MEKi) (maintenance therapy)...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29136952/identification-and-validation-of-cetuximab-resistance-associated-long-noncoding-rna-biomarkers-in-metastatic-colorectal-cancer
#6
Ke Peng, Ruiqi Liu, Yiyi Yu, Li Liang, Shan Yu, Xiaojing Xu, Tianshu Liu
BACKGROUND: Cetuximab is one of the most widely used epidermal growth factor receptor (EGFR) inhibitors to treat patients with metastatic colorectal cancer (mCRC) harboring wild-type of RAS/RAF status. However, primary and acquired resistance to cetuximab is often found during target therapy. METHODS: To gain insights into the functions of long non-coding RNA (lncRNA) in cetuximab resistance, we used a lncRNA-mining approach to distinguish lncRNA specific probes in Affymetrix HG-U133A 2...
November 10, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29128908/cetuximab-tpf-radiotherapy-in-oesophageal-cancer
#7
Maria Alsina, Fernando Rivera, Francisco Javier Ramos, Maica Galán, Rafael López, Pilar García-Alfonso, José Enrique Alés-Martinez, Bernardo Queralt, Antonio Antón, Alfredo Carrato, Cristina Grávalos, Maria José Méndez-Vidal, Carlos López, Inmaculada Ruiz de Mena, Josep Tabernero, Jordi Giralt, Enrique Aranda
BACKGROUND: Pre-operative chemoradiotherapy using a 5-fluorouracil (5-FU)/cisplatin backbone is widely used to improve surgical outcomes in locoregional oesophageal cancer patients, despite a non-negligible failure rate. OBJECTIVE: We evaluated intensification of this approach to improve patient outcomes by adding cetuximab to induction 5-FU/cisplatin/docetaxel (TPF) and to chemoradiotherapy in a phase II study. PATIENTS AND METHODS: Between November 2006 and April 2009, 50 patients with stage II-IVa squamous cell carcinoma (SCC) or adenocarcinoma of the oesophagus or gastro-oesophageal junction initiated three TPF/cetuximab cycles...
November 11, 2017: Targeted Oncology
https://www.readbyqxmd.com/read/29110849/continued-use-of-afatinib-with-the-addition-of-cetuximab-after-progression-on-afatinib-in-patients-with-egfr-mutation-positive-non-small-cell-lung-cancer-and-acquired-resistance-to-gefitinib-or-erlotinib
#8
Leora Horn, Scott Gettinger, D Ross Camidge, Egbert F Smit, Yelena Y Janjigian, Vincent A Miller, William Pao, Matthias Freiwald, Jean Fan, Bushi Wang, Vikram K Chand, Harry J M Groen
OBJECTIVES: In a phase Ib trial, afatinib plus cetuximab demonstrated promising clinical activity (objective response rate [ORR]: 29%; median progression-free survival [PFS]: 4.7 months) in patients with epidermal growth factor receptor (EGFR) mutation-positive non-small-cell lung cancer (NSCLC) with acquired resistance to erlotinib or gefitinib. Here, a separate cohort exploring afatinib plus cetuximab after progression on afatinib is reported. MATERIALS AND METHODS: Patients with EGFR mutation-positive NSCLC who progressed on erlotinib or gefitinib received afatinib 40mg daily until progression, followed by afatinib daily plus cetuximab 500mg/m(2) every 2 weeks until progression or intolerable adverse events (AEs)...
November 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/29104875/a-novel-system-for-the-quantification-of-the-adcc-activity-of-therapeutic-antibodies
#9
Christophe Lallemand, Feifei Liang, Flore Staub, Maud Simansour, Benoit Vallette, Lue Huang, Rosa Ferrando-Miguel, Michael G Tovey
Novel ADCC effector cells expressing the V-variant or F-variant of FcγRIIIa (CD16a) and firefly luciferase under the control of a chimeric promoter incorporating recognition sequences for the principal transcription factors involved in FcγRIIIa signal transduction, together with novel target cells overexpressing a constant high level of the specific antigen recognized by rituximab, trastuzumab, cetuximab, infliximab, adalimumab, or etanercept, confer improved sensitivity, specificity, and dynamic range in an ADCC assay relative to effector cells expressing a NFAT-regulated reporter gene and wild-type target cells...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/29103751/cost-effectiveness-of-nivolumab-for-recurrent-or-metastatic-head-and-neck-cancer%C3%A2
#10
Matthew C Ward, Chirag Shah, David J Adelstein, Jessica L Geiger, Jacob A Miller, Shlomo A Koyfman, Mendel E Singer
OBJECTIVE: Nivolumab is the first drug to demonstrate a survival benefit for platinum-refractory recurrent or metastatic head and neck cancer. We performed a cost-utility analysis to assess the economic value of nivolumab as compared to alternative standard agents in this context. MATERIALS AND METHODS: Using data from the CheckMate 141 trial, we constructed a Markov simulation model from the US payer's perspective to evaluate the cost-effectiveness of nivolumab compared to physician choice of either cetuximab, methotrexate or docetaxel...
November 2017: Oral Oncology
https://www.readbyqxmd.com/read/29100032/extracorporeal-human-whole-blood-in-motion-as-a-tool-to-predict-first-infusion-reactions-and-mechanism-of-action-of-immunotherapeutics
#11
Erika A K Fletcher, Mohamed Eltahir, Frida Lindqvist, Jonas Rieth, Gunilla Törnqvist, Justyna Leja-Jarblad, Sara M Mangsbo
First infusion reactions along with severe anaphylactic responses can occur as a result of systemic administration of therapeutic antibodies. The underlying mechanisms by which monoclonal antibodies induce cytokine release syndrome (CRS) can involve direct agonistic effects via the drug target, or a combination of target-engagement along with innate receptor interactions. Despite the wide variety of pathways and cells that can play a role in CRS, many currently used assays are devoid of one or more components that must be present for these responses to occur...
October 27, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/29094721/colorectal-cancer-mir-100-and-mir-125b-induce-cetuximab-resistance-in-crc
#12
Hugh Thomas
No abstract text is available yet for this article.
November 2, 2017: Nature Reviews. Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/29079308/prognostic-value-of-tissue-necrosis-hypoxia-related-markers-and-correlation-with-hpv-status-in-head-and-neck-cancer-patients-treated-with-bio-or-chemo-radiotherapy
#13
Dan Ou, Ingrid Garberis, Julien Adam, Pierre Blanchard, France Nguyen, Antonin Levy, Odile Casiraghi, Philippe Gorphe, Ingrid Breuskin, François Janot, Stephane Temam, Jean-Yves Scoazec, Eric Deutsch, Yungan Tao
BACKGROUND AND PURPOSE: The aim of the present study was to investigate the role of three hypoxia-related biomarkers in patients with locally advanced head and neck squamous cell carcinoma (HNSCC) treated with concurrent chemoradiotherapy (3-weekly cisplatin) or bioradiotherapy (weekly cetuximab). MATERIAL AND METHODS: In tumor tissue material from 100 patients with known HPV status, we evaluated the extent of tumor necrosis, the expression level of CA-IX and the microvascular density (MVD) measured as the density of CD34+ vascular structures...
October 24, 2017: Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology
https://www.readbyqxmd.com/read/29075194/pharmacogenomics-dna-biomarkers-in-colorectal-cancer-current-update
#14
REVIEW
Nurul-Syakima Ab Mutalib, Najwa F Md Yusof, Shafina-Nadiawati Abdul, Rahman Jamal
Colorectal cancer (CRC) remains as one of the most common cause of worldwide cancer morbidity and mortality. Improvements in surgical modalities and adjuvant chemotherapy have increased the cure rates in early stage disease, but a significant portion of the patients will develop recurrence or advanced disease. The efficacy of chemotherapy of recurrence and advanced CRC has improved significantly over the last decade. Previously, the historical drug 5-fluorouracil was used as single chemotherapeutic agent. Now with the addition of other drugs such as capecitabine, irinotecan, oxaliplatin, bevacizumab, cetuximab, panitumumab, vemurafenib, and dabrafenib, the median survival of patients with advanced CRC has significantly improved from less than a year to the current standard of almost 2 years...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29073892/multiple-criteria-decision-analysis-in-the-context-of-health-technology-assessment-a-simulation-exercise-on-metastatic-colorectal-cancer-with-multiple-stakeholders-in-the-english-setting
#15
Aris Angelis, Gilberto Montibeller, Daniel Hochhauser, Panos Kanavos
BACKGROUND: Multiple criteria decision analysis (MCDA) has appeared as a methodology to address limitations of economic evaluation in health technology assessment (HTA), however there are limited empirical evidence from real world applications. The aim of this study is to test in practice a recently developed MCDA methodological framework known as Advance Value Framework (AVF) through a proof-of-concept case study engaging multiple stakeholders. METHODS: A multi-attribute value theory methodological process was adopted involving problem structuring, model building, model assessment and model appraisal phases...
October 26, 2017: BMC Medical Informatics and Decision Making
https://www.readbyqxmd.com/read/29067591/nanoparticulate-impurities-isolated-from-pharmaceutical-grade-sucrose-are-a-potential-threat-to-protein-stability
#16
Daniel Weinbuch, Mitchel Ruigrok, Wim Jiskoot, Andrea Hawe
PURPOSE: To investigate the effect of nanoparticulate impurities (NPIs) isolated from pharmaceutical-grade sucrose, on the stability of monoclonal antibodies (mAbs). METHODS: NPIs were purified from pharmaceutical-grade sucrose and spiked into trastuzumab, rituximab, infliximab, and cetuximab formulations. The stability of the mAbs as a function of storage time, temperature, and NPI concentration was assessed by visual inspection, flow-imaging microscopy, nanoparticle tracking analysis, size-exclusion chromatography, capillary isoelectric focusing, and intrinsic differential scanning fluorimetry...
October 24, 2017: Pharmaceutical Research
https://www.readbyqxmd.com/read/29066705/-anti-egfr-antibody-combination-chemotherapy-was-effective-against-locally-advanced-ascending-colon-cancer-as-well-as-a-recurrent-lesion-a-case-report
#17
Yasufumi Yamada, Hajime Yokomizo, Yuki Yano, Sachiyo Okayama, Masaya Satake, Arika Ida, Takebumi Usui, Kentaro Yamaguchi, Shunichi Shiozawa, Kazuhiko Yoshimatsu, Takeshi Shimakawa, Takao Katsube, Yoshihiko Naritaka, Hiroyuki Kato
Here we report a case in which a locally advanced ascending colon cancer was successfully treated with anti-EGFR immunotherapy combined with chemotherapy and curative resection, and recurrent cancer was treated with the same chemotherapy. A 71-year-old man was diagnosed with ascending colon cancer in our department. No distant metastasis was observed, but curative resection was considered impossible because of extensive local cancer invasion. Because a genetic analysis revealed the presence of the wild-type KRAS gene, 6 courses of mFOLFOX6 plus cetuximab were administered...
October 2017: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/29064002/cea-response-and-depth-of-response-dpr-to-predict-clinical-outcomes-of-first-line-cetuximab-treatment-for-metastatic-colorectal-cancer
#18
Yu Sunakawa, Akihito Tsuji, Tadamichi Denda, Yoshihiko Segawa, Yuji Negoro, Ken Shimada, Mitsugu Kochi, Masato Nakamura, Masahito Kotaka, Hiroaki Tanioka, Akinori Takagane, Satoshi Tani, Tatsuro Yamaguchi, Takanori Watanabe, Masahiro Takeuchi, Masashi Fujii, Wataru Ichikawa
BACKGROUND: The decrease in carcinoembryonic antigen (CEA) level is faster and greater during cetuximab treatment than bevacizumab treatment and correlates with prolonged survival in patients with metastatic colorectal cancer (mCRC) who receive cetuximab. OBJECTIVE: We investigated if the degree of change in the CEA value can serve as a diagnostic tool for predicting survival, as well as tumor regression in mCRC patients treated with cetuximab combined regimen as first-line treatment...
October 24, 2017: Targeted Oncology
https://www.readbyqxmd.com/read/29061833/anti-epidermal-growth-factor-receptor-antibody-readministration-in-chemorefractory-metastatic-colorectal-cancer
#19
Tatsuhiro Kajitani, Akitaka Makiyama, Shuji Arita, Hozumi Shimokawa, Hisanobu Oda, Tsuyoshi Shirakawa, Eishi Baba, Taito Esaki
BACKGROUND/AIM: Readministration of anti-epidermal growth factor receptor (EGFR) antibody for metastatic colorectal cancer (mCRC) after disease progression remains to be determined. PATIENTS AND METHODS: Readministration of anti-EGFR antibody in mCRC patients previously refractory to anti-EGFR antibody was prospectively observed. RESULTS: A total of thirteen patients with a median age of 60-years old and an Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1, were enrolled...
November 2017: Anticancer Research
https://www.readbyqxmd.com/read/29061643/a-phase-ib-study-of-immune-biomarker-modulation-with-neoadjuvant-cetuximab-and-tlr8-stimulation-in-head-and-neck-cancer-to-overcome-suppressive-myeloid-signals
#20
Gulidanna Shayan, Benjamin A Kansy, Sandra P Gibson, Raghvendra M Srivastava, James Kyle Bryan, Julie E Bauman, James Ohr, Seungwon Kim, David A Clump, Umamaheswar Duvvuri, Dwight E Heron, Jonas T Johnson, Robert Hershberg, Robert L Ferris
PURPOSE: The response rate of head and neck squamous cell carcinoma (HNSCC) patients to cetuximab therapy is only 15-20%, despite frequent EGFR overexpression. Since immunosuppression is common in HNSCC, we hypothesized that adding a pro-inflammatory TLR8 agonist to cetuximab therapy might result in enhanced T lymphocyte stimulation and anti-EGFR specific priming. EXPERIMENTAL DESIGN: Fourteen patients with previously untreated HNSCC were enrolled in this neoadjuvant trial and treated preoperatively with 3-4 weekly doses of motolimod (2...
October 23, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
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