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cetuximab head and neck cancers

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https://www.readbyqxmd.com/read/29035371/lncrna-mir100hg-derived-mir-100-and-mir-125b-mediate-cetuximab-resistance-via-wnt-%C3%AE-catenin-signaling
#1
Yuanyuan Lu, Xiaodi Zhao, Qi Liu, Cunxi Li, Ramona Graves-Deal, Zheng Cao, Bhuminder Singh, Jeffrey L Franklin, Jing Wang, Huaying Hu, Tianying Wei, Mingli Yang, Timothy J Yeatman, Ethan Lee, Kenyi Saito-Diaz, Scott Hinger, James G Patton, Christine H Chung, Stephan Emmrich, Jan-Henning Klusmann, Daiming Fan, Robert J Coffey
De novo and acquired resistance, which are largely attributed to genetic alterations, are barriers to effective anti-epidermal-growth-factor-receptor (EGFR) therapy. To generate cetuximab-resistant cells, we exposed cetuximab-sensitive colorectal cancer cells to cetuximab in three-dimensional culture. Using whole-exome sequencing and transcriptional profiling, we found that the long non-coding RNA MIR100HG and two embedded microRNAs, miR-100 and miR-125b, were overexpressed in the absence of known genetic events linked to cetuximab resistance...
October 16, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28939847/dual-mab-her-family-blockade-in-head-and-neck-cancer-human-cell-lines-combined-with-photon-therapy
#2
Jean-Baptiste Guy, Benoîte Méry, Edouard Ollier, Sophie Espenel, Alexis Vallard, Anne-Sophie Wozny, Stéphanie Simonet, Alexandra Lauret, Priscillia Battiston-Montagne, Dominique Ardail, Gersende Alphonse, Chloé Rancoule, Claire Rodriguez-Lafrasse, Nicolas Magné
Head and neck cancer stem cells (CSCs) are highly resistant to treatment. When EGFR is overexpressed in head and neck squamous cell carcinoma (HNSCC), HER2 and HER3 are also expressed. The aim of the present study was to investigate the effect of HER1/2/3 blockade through a combination of cetuximab and pertuzumab, with or without photon irradiation, on the proliferation and migration/invasion capabilities of an HNSCC chemo- and radioresistant human cell line (SQ20B) and its corresponding stem cell subpopulation...
September 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28932643/clinical-relevance-of-tumor-infiltrating-lymphocytes-pd-l1-expression-and-correlation-with-hpv-p16-in-head-and-neck-cancer-treated-with-bio-or-chemo-radiotherapy
#3
Dan Ou, Julien Adam, Ingrid Garberis, Pierre Blanchard, France Nguyen, Antonin Levy, Odile Casiraghi, Philippe Gorphe, Ingrid Breuskin, François Janot, Stephane Temam, Jean-Yves Scoazec, Eric Deutsch, Yungan Tao
To investigate the prognostic value of tumor infiltrating lymphocytes (TILs: CD8+ and FoxP3+), and PD-L1 expression in patients with head and neck squamous cell carcinoma (HNSCC) treated with radiotherapy combined with cisplatin (CRT) or cetuximab (BRT). Immunohistochemistry for CD8, FoxP3 was performed on pretreatment tissue samples of 77 HNSCC patients. PD-L1 results were evaluable in 38 patients. Cox regression analysis was used to analyze the correlations of these biomarkers expression with clinicopathological characteristics and treatment outcomes...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28932126/dermopathy-associated-with-cetuximab-and-panitumumab-investigation-of-the-usefulness-of-moisturizers-in-its-management
#4
Shoichi Watanabe, Motoki Nakamura, Hiroki Takahashi, Masayasu Hara, Kei Ijichi, Daisuke Kawakita, Akimichi Morita
AIMS: Limited data regarding the objective evaluation of skin exsiccation caused by epidermal growth factor receptor (EGFR) inhibitors exist. Objective indices were applied to evaluate the usefulness of a moisturizer against skin exsiccation associated with the use of EGFR inhibitors in cancer patients. PATIENTS AND METHODS: Patients with either colorectal or head and neck cancer treated with either cetuximab or panitumumab were randomly assigned 1:2 to the prophylactic-treatment arm, where participants received prophylactical moisturizer treatment (heparinoid preparation, Hirudoid(®)), or to the symptomatic-treatment arm, where moisturizer was applied after the onset of cutaneous symptoms...
2017: Clinical, Cosmetic and Investigational Dermatology
https://www.readbyqxmd.com/read/28911070/induction-tpf-followed-by-concomitant-treatment-versus-concomitant-treatment-alone-in-locally-advanced-head-and-neck-cancer-a-phase-ii-iii-trial
#5
M G Ghi, A Paccagnella, D Ferrari, P Foa, D Alterio, C Codecà, F Nolè, E Verri, R Orecchia, F Morelli, S Parisi, C Mastromauro, C A Mione, C Rossetto, M Polsinelli, H Koussis, L Loreggian, A Bonetti, F Campostrini, G Azzarello, C D'Ambrosio, F Bertoni, C Casanova, E Emiliani, M Guaraldi, F Bunkheila, P Bidoli, R M Niespolo, A Gava, E Massa, A Frattegiani, F Valduga, G Pieri, T Cipani, D Da Corte, F Chiappa, E Rulli
Background: Platinum-based chemoradiation (CCRT) is the standard treatment for Locally Advanced Head and Neck Squamous-Cell Carcinoma (LAHNSCC). Cetuximab/RT (CET/RT) is an alternative treatment option to CCRT. The efficacy of induction chemotherapy (IC) followed by chemoradiation compared to chemoradiation alone has not been demonstrated in randomized clinical trials. The goals of this phase II-III trial were to assess: (i) the overall survival (OS) of IC versus no-induction (no-IC) and (ii) the Grade 3-4 in-field mucosal toxicity of CCRT versus CET/RT...
September 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28910149/dual-targeting-of-epidermal-growth-factor-receptor-and-her3-by-mehd7945a-as-monotherapy-or-in-combination-with-cisplatin-partially-overcomes-cetuximab-resistance-in-head-and-neck-squamous-cell-carcinoma-cell-lines
#6
Ines De Pauw, An Wouters, Jolien Van den Bossche, Vanessa Deschoolmeester, Hasan Baysal, Patrick Pauwels, Marc Peeters, Jan B Vermorken, Filip Lardon
Aberrant signaling of the epidermal growth factor receptor (EGFR) plays a crucial role in the tumorigenesis of many cancer types, including head and neck squamous cell carcinoma (HNSCC), making it a compelling drug target. After initial promising results of EGFR-targeted therapies such as cetuximab, the problem of therapeutic resistance is emerging and new treatment options are necessary. In contrast to first-generation EGFR inhibitors, MEHD7945A (duligotuzumab) is a monoclonal antibody with dual EGFR/HER3 specificity...
September 2017: Cancer Biotherapy & Radiopharmaceuticals
https://www.readbyqxmd.com/read/28906000/a-phosphoarray-platform-is-capable-of-personalizing-kinase-inhibitor-therapy-in-head-and-neck-cancers
#7
Konrad Klinghammer, James Keller, Jonathan George, Jens Hoffmann, Edward L Chan, Michael J Hayman
Tyrosine kinase inhibitors are effective treatments for cancers. Knowing the specific kinase mutants that drive the underlying cancers predict therapeutic response to these inhibitors. Thus, the current protocol for personalized cancer therapy involves genotyping tumors in search of various driver mutations and subsequently individualizing the tyrosine kinase inhibitor to the patients whose tumors express the corresponding driver mutant. While this approach works when known driver mutations are found, its limitation is the dependence on driver mutations as predictors for response...
September 14, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28888713/simple-and-rapid-lc-ms-ms-method-for-the-absolute-determination-of-cetuximab-in-human-serum-using-an-immobilized-trypsin
#8
Kaito Shibata, Takafumi Naito, Jun Okamura, Seiji Hosokawa, Hiroyuki Mineta, Junichi Kawakami
Proteomic approaches using liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) without an immunopurification technique have not been applied to the determination of serum cetuximab. This study developed a simple and rapid LC-MS/MS method for the absolute determination of cetuximab in human serum and applied it to clinical settings. Surrogate peptides derived from cetuximab digests were selected using a Fourier transform mass spectrometer. Reduced-alkylated serum cetuximab without immunopurification was digested for 20minutes using immobilized trypsin, and the digestion products were purified by solid-phase extraction...
August 30, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28881692/cabazitaxel-in-recurrent-metastatic-squamous-cell-carcinoma-of-the-head-and-neck-phase-ii-unicancer-trial-orl03
#9
Jerome Fayette, Joel Guigay, Christophe Le Tourneau, Marian Degardin, Frederic Peyrade, Eve-Marie Neidhardt, Marie-Paule Sablin, Caroline Even, Florence Orlandini, Béata Juzyna, Carine Bellera
Treatments are limited after platinum Cetuximab or anti-PD1 failure for patients with recurrent/metastatic head and neck squamous cell carcinoma. Cabazitaxel has increased overall survival in hormone-refractory metastatic prostate cancer after failure of Docetaxel. Our aim was to detect a signal of activity with Cabazitaxel in patients with head and neck cancer who had failed platinum-, Cetuximab- and taxanes-based chemotherapy. This multicenter phase II trial included progressive patients with an ECOG ≤2...
August 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28872582/reduced-cytokine-release-in-ex-vivo-response-to-cilengitide-and-cetuximab-is-a-marker-for-improved-survival-of-head-and-neck-cancer-patients
#10
Susan Cedra, Susanne Wiegand, Marlen Kolb, Andreas Dietz, Gunnar Wichmann
Targeting of αVβ3 and αVβ5 integrins by cilengitide may reduce growth of solid tumors including head and neck squamous cell carcinoma (HNSCC). Preclinical investigations suggest increased activity of cilengitide in combination with other treatment modalities. The only published trial in HNSCC (ADVANTAGE) investigated cisplatin, 5-fluorouracil, and cetuximab (PFE) without or with once (PFE+CIL1W) or twice weekly cilengitide (PFE+CIL2W) in recurrent/metastatic HNSCC. ADVANTAGE showed good tolerability of the cilengitide arms and even lower adverse events (AEs) compared to PFE but not the benefit in overall survival expected based on preclinical data...
September 5, 2017: Cancers
https://www.readbyqxmd.com/read/28866730/egfr-targeted-therapies-in-the-post-genomic-era
#11
Mary Jue Xu, Daniel E Johnson, Jennifer R Grandis
Over 90% of head and neck cancers overexpress the epidermal growth factor receptor (EGFR). In diverse tumor types, EGFR overexpression has been associated with poorer prognosis and outcomes. Therapies targeting EGFR include monoclonal antibodies, tyrosine kinase inhibitors, phosphatidylinositol 3-kinase (PI3K) inhibitors, and antisense gene therapy. Few EGFR-targeted therapeutics are approved for clinical use. The monoclonal antibody cetuximab is a Food and Drug Administration (FDA)-approved EGFR-targeted therapy, yet has exhibited modest benefit in clinical trials...
September 2, 2017: Cancer Metastasis Reviews
https://www.readbyqxmd.com/read/28862218/docetaxel-plus-cisplatin-plus-fluorouracil-versus-carboplatin-plus-fluorouracil-cetuximab-in-first-line-setting-in-patients-with-recurrent-or-metastatic-head-and-neck-squamous-cell-cancer-who-did-not-previously-receive-neoadjuvant-or-adjuvant-chemotherapy-which
#12
Hasan Mutlu, Derya Kıvrak Salim, Şeyda Gündüz, Melek Karakurt Eryılmaz, Fatma Yalçın Musri, Hasan Şenol Coşkun
BACKGROUND: The prognosis of recurrent or metastatic head and neck squamous cell cancer (HNSCC) is very poor. In the present retrospective study, we compared the impact of docetaxel plus cisplatin plus fluorouracil (TCF), and cisplatin plus fluorouracil plus cetuximab (CF-Ctx) regimens on the prognosis of patients with recurrent or metastatic HNSCC in first-line. MATERIALS AND METHODS: A total of 70 patients were evaluated as two groups, according to treatment protocol: TCF (n: 47) and CF-Ctx (n: 23)...
July 2017: Journal of Cancer Research and Therapeutics
https://www.readbyqxmd.com/read/28860859/head-and-neck-cancer-improving-outcomes-with-a-multidisciplinary-approach
#13
REVIEW
Cristiana Lo Nigro, Nerina Denaro, Anna Merlotti, Marco Merlano
For early-stage head and neck cancer (HNC), surgery (S) or radiotherapy (RT) is a standard treatment. The multidisciplinary approach, which includes multimodality treatment with S followed by RT, with or without chemotherapy (CT) or concurrent chemoradiotherapy (CRT), is required for locally advanced head and neck cancer (LAHNC). CRT improves prognosis, locoregional control (LRC), and organ function in LAHNC, compared to RT alone. Prognosis in recurrent/metastatic HNC (R/M HNC) is dismal. Platinum-based CT, combined with the anti-Epidermal Growth Factor Receptor (EGFR) antibody (Ab) cetuximab, is used in first-line setting, while no further validated options are available at progression...
2017: Cancer Management and Research
https://www.readbyqxmd.com/read/28808428/a-comparison-of-concurrent-cisplatin-versus-cetuximab-with-radiotherapy-in-locally-advanced-head-and-neck-cancer-a-bi-institutional-analysis
#14
William A Stokes, Whitney A Sumner, Kiersten L Breggren, John T Rathbun, David Raben, Jessica D McDermott, Gregory Gan, Sana D Karam
AIM: To present our experience comparing cisplatin- and cetuximab-based radiotherapy for locally-advanced head and neck squamous cell carcinoma. BACKGROUND: The comparative effectiveness of cisplatin-based chemoradiotherapy (CRT) versus cetuximab-based bioradiotherapy (BRT) for locally-advanced head and neck squamous cell carcinoma (LAHNSCC) continues to be explored. MATERIALS AND METHODS: Outcomes of LAHNSCC patients treated with CRT (125) or BRT (34) at two institutions were compared retrospectively, with attention to overall survival (OS), cancer-specific survival (CSS), locoregional control (LRC), and distant control (DC)...
September 2017: Reports of Practical Oncology and Radiotherapy
https://www.readbyqxmd.com/read/28774062/targeted-magnetic-nanoparticles-for-mechanical-lysis-of-tumor-cells-by-low-amplitude-alternating-magnetic-field
#15
Adi Vegerhof, Eran A Barnoy, Menachem Motiei, Dror Malka, Yossef Danan, Zeev Zalevsky, Rachela Popovtzer
Currently available cancer therapies can cause damage to healthy tissue. We developed a unique method for specific mechanical lysis of cancer cells using superparamagnetic iron oxide nanoparticle rotation under a weak alternating magnetic field. Iron oxide core nanoparticles were coated with cetuximab, an anti-epidermal growth factor receptor antibody, for specific tumor targeting. Nude mice bearing a head and neck tumor were treated with cetuximab-coated magnetic nanoparticles (MNPs) and then received a 30 min treatment with a weak external alternating magnetic field (4 Hz) applied on alternating days (total of seven treatments, over 14 days)...
November 22, 2016: Materials
https://www.readbyqxmd.com/read/28764598/two-cases-of-combination-therapy-with-cetuximab-paclitaxel-and-cisplatin-for-advanced-head-and-neck-cancer
#16
Matthew A Hoch, Kati Cousins, Ruth Nartey, Keith Riley, Megan Hartranft
Two patients diagnosed with advanced head and neck cancer were treated with cetuximab 400 mg/m(2) intravenously for one loading dose followed by 250 mg/m(2) IV on days 1, 8, and 15 along with paclitaxel 80 mg/m(2) and cisplatin 30 mg/m(2) intravenously on days 1 and 8 repeated every 21 days for three cycles (CPP). Maintenance cetuximab 250 mg/m(2) intravenously weekly was continued following the aforementioned regimen for one year or until disease progression. Patient A was diagnosed with squamous cell carcinoma of the parotid gland treated initially with parotidectomy and radiation therapy...
January 1, 2017: Journal of Oncology Pharmacy Practice
https://www.readbyqxmd.com/read/28741444/mild-pulmonary-emphysema-a-risk-factor-for-interstitial-lung-disease-when-using-cetuximab-for-squamous-cell-carcinoma-of-the-head-and-neck
#17
Isaku Okamoto, Kiyoaki Tsukahara, Hiroki Sato, Ray Motohashi, Daisuke Yunaiyama, Akira Shimizu
BACKGROUND: Interstitial lung disease (ILD) is an occasionally fatal adverse event associated with cetuximab (Cmab) therapy. Our objective was to clarify to what degree pulmonary emphysema is a risk factor in the treatment of head and neck cancer with Cmab through a retrospective analysis. METHODS: Subjects were 116 patients who were administered Cmab for head and neck squamous cell carcinoma. The degree of pulmonary emphysema before initiating treatment with Cmab was visually assessed retrospectively, with scoring according to the Goddard classification used in Japanese chronic obstructive pulmonary disease (COPD) guidelines for chest computed tomography (CT)...
December 2017: Acta Oto-laryngologica
https://www.readbyqxmd.com/read/28719596/the-influence-of-fcgr2a-and-fcgr3a-polymorphisms-on-the-survival-of-patients-with-recurrent-or-metastatic-squamous-cell-head-and-neck-cancer-treated-with-cetuximab
#18
T Magnes, T Melchardt, C Hufnagl, L Weiss, C Mittermair, D Neureiter, E Klieser, G Rinnerthaler, S Roesch, A Gaggl, R Greil, A Egle
FCGR2A-H131R and FCGR3A-V157F are single-nucleotide polymorphisms known to influence the outcome of patients treated with rituximab, cetuximab and trastuzumab. We investigated the impact of these polymorphisms on the clinical outcome of 103 patients with recurrent or metastatic squamous cell carcinoma of the head and neck treated with a platinum compound, fluorouracil and cetuximab as palliative first-line therapy. The survival of patients with FCGR2A-131H/H and/or FCGR3A-157V/V genotypes was significantly longer compared with patients carrying 131R and 157F alleles (median progression-free survival (PFS): 5...
July 18, 2017: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/28674498/nimotuzumab-induces-nk-cell-activation-cytotoxicity-dendritic-cell-maturation-and-expansion-of-egfr-specific-t-cells-in-head-and-neck-cancer-patients
#19
Zaima Mazorra, Anabel Lavastida, Fernando Concha-Benavente, Anet Valdés, Raghvendra M Srivastava, Tatiana M García-Bates, Esperanza Hechavarría, Zuyen González, Amnely González, Martha Lugiollo, Iván Cuevas, Carlos Frómeta, Braulio F Mestre, Maria C Barroso, Tania Crombet, Robert L Ferris
Survival benefit and long-term duration of clinical response have been seen using the epidermal growth factor receptor (EGFR)-targeted monoclonal antibody (mAb) nimotuzumab. Blocking EGFR signaling may not be the only mechanism of action underlying its efficacy. As an IgG1 isotype mAb, nimotuzumab's capacity of killing tumor cells by antibody dependent cellular cytotoxicity (ADCC) and to induce an immune response in cancer patients have not been studied. ADCC-induced by nimotuzumab was determined using a (51)Cr release assay...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28651929/nivolumab-versus-standard-single-agent-therapy-of-investigator-s-choice-in-recurrent-or-metastatic-squamous-cell-carcinoma-of-the-head-and-neck-checkmate-141-health-related-quality-of-life-results-from-a-randomised-phase-3-trial
#20
RANDOMIZED CONTROLLED TRIAL
Kevin J Harrington, Robert L Ferris, George Blumenschein, A Dimitrios Colevas, Jérôme Fayette, Lisa Licitra, Stefan Kasper, Caroline Even, Everett E Vokes, Francis Worden, Nabil F Saba, Naomi Kiyota, Robert Haddad, Makoto Tahara, Viktor Grünwald, James W Shaw, Manish Monga, Mark Lynch, Fiona Taylor, Michael DeRosa, Laura Morrissey, Kim Cocks, Maura L Gillison, Joël Guigay
BACKGROUND: Patients with platinum-refractory recurrent or metastatic squamous cell carcinoma of the head and neck have few treatment options and poor prognosis. Nivolumab significantly improved survival of this patient population when compared with standard single-agent therapy of investigator's choice in Checkmate 141; here we report the effect of nivolumab on patient-reported outcomes (PROs). METHODS: CheckMate 141 was a randomised, open-label, phase 3 trial in patients with recurrent or metastatic squamous cell carcinoma of the head and neck who progressed within 6 months after platinum-based chemotherapy...
August 2017: Lancet Oncology
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