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cetuximab head and neck cancers

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https://www.readbyqxmd.com/read/29931076/effect-of-adding-motolimod-to-standard-combination-chemotherapy-and-cetuximab-treatment-of-patients-with-squamous-cell-carcinoma-of-the-head-and-neck-the-active8-randomized-clinical-trial
#1
Robert L Ferris, Nabil F Saba, Barbara J Gitlitz, Robert Haddad, Ammar Sukari, Prakash Neupane, John C Morris, Krzysztof Misiukiewicz, Julie E Bauman, Moon Fenton, Antonio Jimeno, Douglas R Adkins, Charles J Schneider, Assuntina G Sacco, Keisuke Shirai, Daniel W Bowles, Michael Gibson, Tobenna Nwizu, Raphael Gottardo, Kristi L Manjarrez, Gregory N Dietsch, James Kyle Bryan, Robert M Hershberg, Ezra E W Cohen
Importance: Immunotherapy for recurrent and/or metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN) is promising. The toll-like receptor 8 (TLR8) agonist motolimod may stimulate innate and adaptive immunity. Objective: To determine whether motolimod improves outcomes for R/M SCCHN when combined with standard therapy. Design, Setting, and Participants: The Active8 study was a multicenter, randomized, double-blind, placebo-controlled clinical trial enrolling adult patients (age ≥18 years) with histologically confirmed R/M SCCHN of the oral cavity, oropharynx, hypopharynx, or larynx between October 2013 and August 2015...
June 21, 2018: JAMA Oncology
https://www.readbyqxmd.com/read/29909889/gene-signatures-and-expression-of-mirnas-associated-with-efficacy-of-panitumumab-in-a-head-and-neck-cancer-phase-ii-trial
#2
Marco Siano, Vittoria Espeli, Nicolas Mach, Paolo Bossi, Lisa Licitra, Michele Ghielmini, Milo Frattini, Silvana Canevari, Loris De Cecco
OBJECTIVE: Platinum-based chemotherapy plus the anti-EGFR monoclonal antibody (mAb) cetuximab is used to treat recurrent/metastatic (RM) head-neck squamous cell carcinoma (HNSCC). Recently, we defined Cluster3 gene-expression signature as a potential predictor of favorable progression-free survival (PFS) in cetuximab-treated RM-HNSCC patients and predictor of partial metabolic FDG-PET response in an afatinib window-of-opportunity trial. Another anti-EGFR-mAb (panitumumab) was used as the treatment agent in RM-HNSCC patients in the phase II PANI01trial...
July 2018: Oral Oncology
https://www.readbyqxmd.com/read/29848571/inhibition-of-ephb4-ephrin-b2-signaling-enhances-response-to-cetuximab-radiation-therapy-in-head-and-neck-cancers
#3
Shilpa Bhatia, Jaspreet Sharma, Sanjana Bukkapatnam, Ayman Oweida, Shelby Lennon, Andy V Phan, Dallin Milner, Nomin Uyanga, Antonio Jimeno, David Raben, Hilary Somerset, Lynn Heasley, Sana D Karam
PURPOSE: The clinical success of targeted therapies such as cetuximab and radiation (RT) is hampered by the low response rates and development of therapeutic resistance. In the current study, we investigated the involvement of EphB4-ephrin-B2 pro-tumorigenic signaling in mediating resistance to EGFR inhibition and radiation therapy in head and neck cancers. EXPERIMENTAL DESIGN: We used patient-derived xenograft (PDX) models of head and neck squamous cell carcinoma (HNSCC) and HNSCC cell lines to test our hypothesis...
May 30, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29792310/bet-inhibition-overcomes-receptor-tyrosine-kinase-mediated-cetuximab-resistance-in-hnscc
#4
Brandon Leonard, Toni M Brand, Rachel A O'Keefe, Eliot Lee, Yan Zang, Jacquelyn D Kemmer, Hua Li, Jennifer R Grandis, Neil E Bhola
Cetuximab, the FDA-approved anti-EGFR antibody for head and neck squamous cell carcinoma (HNSCC), has displayed limited efficacy due to the emergence of intrinsic and acquired resistance. We and others have demonstrated that cetuximab resistance in HNSCC is driven by alternative receptor tyrosine kinases (RTK) including HER3, MET, and AXL. In an effort to overcome cetuximab resistance and circumvent toxicities associated with the administration of multiple RTK inhibitors, we sought to identify a common molecular target that regulates expression of multiple RTK...
May 23, 2018: Cancer Research
https://www.readbyqxmd.com/read/29792227/integrated-time-course-omics-analysis-distinguishes-immediate-therapeutic-response-from-acquired-resistance
#5
Genevieve Stein-O'Brien, Luciane T Kagohara, Sijia Li, Manjusha Thakar, Ruchira Ranaweera, Hiroyuki Ozawa, Haixia Cheng, Michael Considine, Sandra Schmitz, Alexander V Favorov, Ludmila V Danilova, Joseph A Califano, Evgeny Izumchenko, Daria A Gaykalova, Christine H Chung, Elana J Fertig
BACKGROUND: Targeted therapies specifically act by blocking the activity of proteins that are encoded by genes critical for tumorigenesis. However, most cancers acquire resistance and long-term disease remission is rarely observed. Understanding the time course of molecular changes responsible for the development of acquired resistance could enable optimization of patients' treatment options. Clinically, acquired therapeutic resistance can only be studied at a single time point in resistant tumors...
May 23, 2018: Genome Medicine
https://www.readbyqxmd.com/read/29777587/epidermal-growth-factor-receptor-egfr-density-may-not-be-the-only-determinant-for-the-efficacy-of-egfr-targeted-photoimmunotherapy-in-human-head-and-neck-cancer-cell-lines
#6
Wei Peng, Henriette S de Bruijn, Eric Farrell, Mouldy Sioud, Vida Mashayekhi, Sabrina Oliveira, Go M van Dam, Jan L N Roodenburg, Max J H Witjes, Dominic J Robinson
OBJECTIVE: The aim of this study was to investigate the effects of targeted photoimmunotherapy (PIT) in vitro on cell lines with various expression levels of epidermal growth factor receptor (EGFR) using an anti-EGFR targeted conjugate composed of Cetuximab and IR700DX, phthalocyanine dye. MATERIALS AND METHODS: Relative EGFR density and cell binding assay was conducted in three human head & neck cancer cell lines (scc-U2, scc-U8, and OSC19) and one reference cell line A431...
May 19, 2018: Lasers in Surgery and Medicine
https://www.readbyqxmd.com/read/29721181/near-infrared-photoimmunotherapy-targeting-bladder-cancer-with-a-canine-anti-epidermal-growth-factor-receptor-egfr-antibody
#7
Tadanobu Nagaya, Shuhei Okuyama, Fusa Ogata, Yasuhiro Maruoka, Deborah W Knapp, Sophia N Karagiannis, Judit Fazekas-Singer, Peter L Choyke, Amy K LeBlanc, Erika Jensen-Jarolim, Hisataka Kobayashi
Anti-epidermal growth factor receptor (EGFR) antibody therapy is used in EGFR expressing cancers including lung, colon, head and neck, and bladder cancers, however results have been modest. Near infrared photoimmunotherapy (NIR-PIT) is a highly selective tumor treatment that employs an antibody-photo-absorber conjugate which is activated by NIR light. NIR-PIT is in clinical trials in patients with recurrent head and neck cancers using cetuximab-IR700 as the conjugate. However, its use has otherwise been restricted to mouse models...
April 10, 2018: Oncotarget
https://www.readbyqxmd.com/read/29721094/safety-of-panitumumab-irdye800cw-and-cetuximab-irdye800cw-for-fluorescence-guided-surgical-navigation-in-head-and-neck-cancers
#8
Rebecca W Gao, Nutte Teraphongphom, Esther de Boer, Nynke S van den Berg, Vasu Divi, Michael J Kaplan, Nicholas J Oberhelman, Steven S Hong, Elissa Capes, A Dimitrios Colevas, Jason M Warram, Eben L Rosenthal
Purpose: To demonstrate the safety and feasibility of leveraging therapeutic antibodies for surgical imaging. Procedures: We conducted two phase I trials for anti-epidermal growth factor receptor antibodies cetuximab-IRDye800CW (n=12) and panitumumab-IRDye800CW (n=15). Adults with biopsy-confirmed head and neck squamous cell carcinoma scheduled for standard-of-care surgery were eligible. For cetuximab-IRDye800CW, cohort 1 was intravenously infused with 2.5 mg/m2 , cohort 2 received 25 mg/m2 , and cohort 3 received 62...
2018: Theranostics
https://www.readbyqxmd.com/read/29719593/whole-exome-sequencing-identifies-mtor-and-keap1-as-potential-targets-for-radiosensitization-of-hnscc-cells-refractory-to-egfr-and-%C3%AE-1-integrin-inhibition
#9
Erik Klapproth, Ellen Dickreuter, Falk Zakrzewski, Michael Seifert, Andreas Petzold, Andreas Dahl, Evelin Schröck, Barbara Klink, Nils Cordes
Intrinsic and acquired resistances are major obstacles in cancer therapy. Genetic characterization is commonly used to identify predictive or prognostic biomarker signatures and potential cancer targets in samples from therapy-naïve patients. By far less common are such investigations to identify specific, predictive and/or prognostic gene signatures in patients or cancer cells refractory to a specific molecular-targeted intervention. This, however, might have a great value to foster the development of tailored, personalized cancer therapy...
April 6, 2018: Oncotarget
https://www.readbyqxmd.com/read/29709262/new-therapies-in-head-and-neck-cancer
#10
REVIEW
Rodell T Santuray, Daniel E Johnson, Jennifer R Grandis
Head and neck squamous cell carcinoma (HNSCC) is a common malignancy with high rates of mortality and morbidity. Beginning with cetuximab, investigators continue to optimize antibody technology to target cell-surface receptors that promote HNSCC growth. Small molecules and oligonucleotides have also emerged as therapeutic inhibitors of key receptor-mediated signaling pathways. Although many such therapies have been disappointing in clinical trials as single agents, they continue to be studied in combination with standard therapies...
May 2018: Trends in Cancer
https://www.readbyqxmd.com/read/29706187/locally-advanced-squamous-cell-carcinoma-of-the-head-and-neck-a-systematic-review-and-bayesian-network-meta-analysis-of-the-currently-available-treatment-options
#11
Oreste Iocca, Alessio Farcomeni, Arianna Di Rocco, Pasquale Di Maio, Paweł Golusinski, Simón Pardiñas López, Alfredo Savo, Raul Pellini, Giuseppe Spriano
BACKGROUND: There are still many unresolved questions in the management of locally advanced Head and Neck Cancer (HNC). Many chemotherapeutic drugs and radiotherapy fractionation schemes are available and not all have been evaluated in head-to-head clinical trials. This systematic review and Bayesian network meta-analysis aims to compare the available treatment strategies and chemotherapeutic options for locally advanced HNC. METHODS: We performed a search on bibliography databases, trials registries and meetings proceedings for published and unpublished randomized trials from January 1st 2000 to December 1st 2017...
May 2018: Oral Oncology
https://www.readbyqxmd.com/read/29650896/-the-combination-of-molecular-targeted-agents-with-radiotherapy-in-head-and-neck-cancer
#12
Mitsuhiro Furuta, Tomoya Yokota
Concurrent cisplatin based chemoradiotherapy(CRT)is the standard of care for patients with locoregionally advanced squamous cell carcinoma of the head and neck(LA-SCCHN). Based on the Bonner trial showing the superiority of cetuximab plus radiotherapy to radiotherapy alone, cetuximab based bioradiotherapy(BRT)is considered as an alternative for patients with LA-SCCHN. However, the non-inferiority of BRT compared to CRT has not yet been demonstrated. Furthermore, severe mucositis and dermatitis induced by BRT cannot be neglected...
March 2018: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/29604587/apigenin-enhances-the-antitumor-effects-of-cetuximab-in-nasopharyngeal-carcinoma-by-inhibiting-egfr-signaling
#13
Wen-Jian Hu, Jing Liu, Lun-Kun Zhong, Jian Wang
Nasopharyngeal carcinoma (NPC) is a type of head and neck cancers with poor prognosis. Despite that platinum-based chemotherapy concurrent with radiotherapy have made great achievements for the treatment of NPC, the therapeutic reaction and toxicity varies dramatically among individuals. Apigenin (API), a naturally occurring plant flavone, is considered to have anti-cancer effect. Cetuximab (CET), a well known epidermal growth factor receptor (EGFR) inhibitor, is widely used in various cancers, especially head and neck cancers...
June 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29568372/effects-of-cetuximab-and-erlotinib-on-the-behaviour-of-cancer-stem-cells-in-head-and-neck-squamous-cell-carcinoma
#14
Maria Fernanda Setúbal Destro Rodrigues, Luke Gammon, Muhammad M Rahman, Adrian Biddle, Fabio Daumas Nunes, Ian C Mackenzie
The therapeutic responses of many solid tumours to chemo- and radio-therapies are far from fully effective but therapies targeting malignancy-related cellular changes show promise for further control. In head and neck squamous cell carcinoma, the epidermal growth factor receptor (EGFR) is commonly overexpressed and investigation of agents that block this receptor indicate a limited response when used alone but an ability to enhance the actions of other drugs. The hierarchical stem cell patterns present in tumours generate cellular heterogeneity and this is further complicated by cancer stem cells (CSC) shifting between epithelial (Epi-CSC) and mesenchymal (EMT-CSC) states...
March 2, 2018: Oncotarget
https://www.readbyqxmd.com/read/29556677/a-feasibility-study-on-adaptive-18-f-fdg-pet-guided-radiotherapy-for-recurrent-and-second-primary-head-and-neck-cancer-in-the-previously-irradiated-territory
#15
Julie Schatteman, Dirk Van Gestel, Dieter Berwouts, Werner De Gersem, Geert De Kerf, Wilfried De Neve, Bie De Ost, Ana Maria Luiza Olteanu, Sylvie Rottey, Tom Vercauteren, Ingeborg Goethals, Fréderic Duprez
PURPOSE: To evaluate feasibility, disease control, survival, and toxicity after adaptive 18 F-fluorodeoxyglucose (FDG) positron emisson tomography (PET) guided radiotherapy in patients with recurrent and second primary head and neck squamous cell carcinoma. METHODS: A prospective trial investigated the feasibility of adaptive intensity modulated radiotherapy (IMRT) ± concomitant cetuximab in 10 patients. The primary endpoint was achieving a 2-year survival free of grade >3 toxicity in ≥30% of patients...
March 19, 2018: Strahlentherapie und Onkologie: Organ der Deutschen Röntgengesellschaft ... [et Al]
https://www.readbyqxmd.com/read/29552307/characterization-of-7a7-an-anti-mouse-egfr-monoclonal-antibody-proposed-to-be-the-mouse-equivalent-of-cetuximab
#16
Xuzhi He, Jazmina L Cruz, Shannon Joseph, Nicola Pett, Hui Yi Chew, Zewen K Tuong, Satomi Okano, Gabrielle Kelly, Margaret Veitch, Fiona Simpson, James W Wells
The Epidermal Growth Factor Receptor (EGFR) is selectively expressed on the surface of numerous tumours, such as non-small cell lung, ovarian, colorectal and head and neck carcinomas. EGFR has therefore become a target for cancer therapy. Cetuximab is a chimeric human/mouse monoclonal antibody (mAb) that binds to EGFR, where it both inhibits signaling and induces cell death by antibody-dependent cell mediated cytotoxicity (ADCC). Cetuximab has been approved for clinical use in patients with head and neck squamous cell carcinoma (HNSCC) and colorectal cancer...
February 23, 2018: Oncotarget
https://www.readbyqxmd.com/read/29541413/combined-modality-radiation-therapy-promotes-tolerogenic-myeloid-cell-populations-and-stat3-related-gene-expression-in-head-and-neck-cancer-patients
#17
Sagus Sampath, Haejung Won, Erminia Massarelli, Min Li, Paul Frankel, Nayana Vora, Lalit Vora, Ellie Maghami, Marcin Kortylewski
Immunomodulation contributes to the antitumor efficacy of the fractionated radiation therapy (RT). Here, we describe immune effects of RT with concurrent systemic cisplatin or cetuximab treatment of patients with stage III-IV head and neck squamous cell carcinoma (HNSCC). Using longitudinally collected blood samples, we identified significant changes in cytokines/chemokines and immune cell populations compared to immune-related gene expression profiles in peripheral blood mononuclear cells (PBMCs). The 7-week combinatorial RT resulted in gradual elevation of proinflammatory mediators (IFNγ, IL-6, TNFɑ, CCL2), while levels of IL-12, cytokine essential for antitumor immune responses, were decreased...
February 16, 2018: Oncotarget
https://www.readbyqxmd.com/read/29540490/stat3-hotair-signaling-axis-regulates-hnscc-growth-in-an-ezh2-dependent-manner
#18
Shanshan Sun, Yansheng Wu, Wenyu Guo, Feng Yu, Lingping Kong, Yu Ren, Yu Wang, Xiaofeng Yao, Chao Jing, Chao Zhang, Mingyang Liu, Yuqing Zhang, Minghui Zhao, Zhaoqing Li, Chuanqiang Wu, Yu Qiao, Jingxuan Yang, Xudong Wang, Lun Zhang, Min Li, Xuan Zhou
Purpose: PI3K and STAT3 are frequently activated in cancer progression. However, little is known about the underlying mechanisms by which PI3K and STAT3 regulate head and neck squamous cell cancer (HNSCC) growth. The lncRNA HOX transcript antisense RNA ( HOTAIR ) was found to modulate the progression of HNSCC. In this study, we attempted to establish the correlation of PI3K/STAT3/HOTAIR signaling with the progression of HNSCC and its sensitivity toward platinum-based and targeted anti-EGFR combination therapy...
March 14, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29537684/cost-effectiveness-analysis-of-salvage-therapies-in-locoregional-previously-irradiated-head-and-neck-cancer
#19
HaYeon Kim, John A Vargo, Sushil Beriwal, David A Clump, James P Ohr, Robert L Ferris, Dwight E Heron, M Saiful Huq, Kenneth J Smith
BACKGROUND: The purpose of this study was to present our evaluation of the cost-effectiveness of salvage therapies for patients with recurrent head and neck cancer. METHODS: A Markov model was developed with 5 salvage treatment strategies: (1) platinum-based chemotherapy alone; (2) chemotherapy plus cetuximab; (3) stereotactic body radiotherapy (SBRT) alone; (4) SBRT plus cetuximab; and (5) intensity-modulated radiotherapy (IMRT) plus chemotherapy. Clinical parameters were obtained from comprehensive literature review and 2016 Medicare reimbursement...
March 14, 2018: Head & Neck
https://www.readbyqxmd.com/read/29534625/cetuximab-for-treating-non-small-cell-lung-cancer
#20
Luca Mazzarella, Alessandro Guida, Giuseppe Curigliano
Epidermal Growth Factor Receptor (EGFR)-dependent signaling plays a crucial role in epithelial cancer biology, and dictated the development of several targeting agents. The mouse-human chimeric antibody Cetuximab was among the first to be developed. After about two decades of clinical research it has gained a significant place in the management of advanced colorectal and head and neck cancers, whereas its development in non small cell lung cancer (NSCLC) has not led to a place in routine clinical practice, because of marginal clinical benefit despite statistically significant Phase III trials...
April 2018: Expert Opinion on Biological Therapy
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