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cetuximab head and neck cancers

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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
#1
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
#2
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
#3
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...
June 23, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28628728/characterizing-the-detection-threshold-for-optical-imaging-in-surgical-oncology
#4
Andrew C Prince, Aditi Jani, Melissa Korb, Kiranya E Tipirneni, Benjamin B Kasten, Eben L Rosenthal, Jason M Warram
BACKGROUND AND OBJECTIVES: Optical imaging to guide cancer resections is rapidly transitioning into the operating room. However, the sensitivity of this technique to detect subclinical disease is yet characterized. The purpose of this study was to determine the minimum range of cancer cells that can be detected by antibody-based fluorescence imaging. METHODS: 2LMP (breast), COLO-205 (colon), MiaPaca-2 (pancreas), and SCC-1 (head and neck) cells incubated in vitro with cetuximab-IRDye800CW (dose range 8...
June 19, 2017: Journal of Surgical Oncology
https://www.readbyqxmd.com/read/28606015/retrospective-analysis-of-premedication-glucocorticosteroids-and-h1-antihistamines-for-preventing-infusion-reactions-associated-with-cetuximab-treatment-of-patients-with-head-and-neck-cancer
#5
Kiwako Ikegawa, Shinya Suzuki, Hisanaga Nomura, Tomohiro Enokida, Tomoko Yamazaki, Susumu Okano, Kazushi Endo, Shinichiro Saito, Masakazu Yamaguchi, Makoto Tahara
Objectives We evaluated infusion-related reactions associated with cetuximab combination chemotherapy comprising an H1-receptor antagonist plus dexamethasone as anti-allergy premedications for patients with head and neck cancer. Methods We retrospectively evaluated 248 patients who received a cetuximab combination regimen between December 2012 and August 2015. All patients received 5 mg intravenous dichlorpheniramine (H1-receptor antagonist), and dexamethasone (DEX) was adjusted from 6.6 mg to 13.2 mg according to the emetogenic risk...
January 1, 2017: Journal of International Medical Research
https://www.readbyqxmd.com/read/28602169/toxicities-of-systemic-agents-in-squamous-cell-carcinoma-of-the-head-and-neck-scchn-a-new-perspective-in-the-era-of-immunotherapy
#6
REVIEW
Nabil F Saba, Mayur D Mody, Elaine S Tan, Harpaul S Gill, Alessandra Rinaldo, Robert P Takes, Primož Strojan, Dana M Hartl, Jan B Vermorken, Missak Haigentz, Alfio Ferlito
Squamous cell carcinoma of the head and neck (SCCHN) is a difficult to treat malignancy and represents the seventh most common cancer worldwide. Systemic therapy has a critical role in the treatment of locally advanced and recurrent/metastatic disease. Cytotoxic chemotherapy has been primarily used along with radiation and surgery, with cisplatin being the standard of care choice of therapy. When contraindications to cisplatin exist, other agents such as carboplatin, taxanes, 5-fluorouracil, and cetuximab are used...
July 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28598813/identification-of-a-novel-atm-inhibitor-with-cancer-cell-specific-radiosensitization-activity
#7
Amy J C Dohmen, Xiaohang Qiao, Anja Duursma, Ruud H Wijdeven, Cor Lieftink, Floor Hageman, Ben Morris, Pasi Halonen, Conchita Vens, Michiel W M van den Brekel, Huib Ovaa, Jacques Neefjes, Charlotte L Zuur
Treatment of advanced head and neck squamous cell carcinoma (HNSCC) is plagued by low survival and high recurrence rates, despite multimodal therapies. Presently, cisplatin or cetuximab is used in combination with radiotherapy which has resulted in minor survival benefits but increased severe toxicities relative to RT alone. This underscores the urgent need for improved tumor-specific radiosensitizers for better control with lower toxicities. In a small molecule screen targeting kinases, performed on three HNSCC cell lines, we identified GSK635416A as a novel radiosensitizer...
May 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/28597041/efficacy-and-safety-of-postoperative-bio-chemoradiotherapy-using-cetuximab-and-docetaxel-for-high-risk-head-and-neck-cancer-patients-in-japan
#8
Goshi Nishimura, Osamu Shiono, Daisuke Sano, Kenichiro Yabuki, Yasuhiro Arai, Yoshihiro Chiba, Teruhiko Tanabe, Nobuhiko Oridate
PURPOSE: To confirm the efficacy and safety of cetuximab and docetaxel in postoperative radiotherapy for high-risk head and neck cancer patients who cannot to be administered high-dose cisplatin. PATIENTS AND METHODS: The eligibility criteria required stage III-IVB head and neck cancer patients who had undergone total resection, and for whom pathological evaluation revealed positive or close margins in the primary site and/or extracapsular nodal extension and/or two or more nodal metastases...
July 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28588776/management-of-infusion-reactions-associated-with-cetuximab-treatment-a-case-report
#9
Naohiro Ohshita, Yuri Ichimaru, Shoko Gamoh, Kaname Tsuji, Naotaka Kishimoto, Yasuo M Tsutsumi, Yoshihiro Momota
Cetuximab is a drug targeting the epidermal growth factor receptor, which is indicated for the treatment of unresectable advanced or recurrent head and neck or colorectal cancer. Cetuximab also enhances the cytotoxic effects of radiation in squamous cell carcinoma. The severity of infusion reactions (IR) is categorized from grade 1 to 5; grades 3 and 4 are associated with life-threatening reactions (anaphylaxis), whereas grade 5 indicates death. The incidence of grade 3-4 IR with premedication is reported to be 1...
June 2017: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/28588721/palliative-treatment-of-patients-with-inoperable-locally-advanced-recurrent-or-metastatic-head-and-neck-squamous-cell-cancer-using-a-low-dose-and-personalized-chemotherapeutic-regimen
#10
Rohit Bishnoi, Jeffery Bennett, David N Reisman
Inoperable or metastatic head and neck squamous cell cancer (HNSCC) is known to be associated with a poor patient prognosis. First line therapies include a Taxol, platinum-based antineoplastic and fluorouracil (FU) treatment regimen (TPF) or a platinum-based antineoplastic, FU and EGFR inhibitor treatment regimen (PFE). The toxicity of these regimens is one of the major limiting factors, particularly for palliative treatment. The present study is a retrospective study of 15 patients with HNSCC, where the treatment goal was palliative...
June 2017: Oncology Letters
https://www.readbyqxmd.com/read/28580506/prolonged-overall-treatment-time-and-lack-of-skin-rash-negatively-impact-overall-survival-in-locally-advanced-head-and-neck-cancer-patients-treated-with-radiotherapy-and-concomitant-cetuximab
#11
Julien Roman, Gurvan Dissaux, Maelenn Gouillou, Yves Gobel, Gael Potard, Jean-Christophe Leclere, Virginie Conan-Charlet, Dorothy Gujral, Ronan Abgral, Briac Guibourg, Olivier Pradier, Ulrike Schick
BACKGROUND: Cetuximab, a chimeric monoclonal antibody against EGFR sensitizes tumors to radiotherapy (RT), but is associated with skin and mucosal toxicity. OBJECTIVE: We report outcomes and tolerance of definitive RT in association with cetuximab in patients with locally advanced squamous cell carcinoma (LASCC) of the head and neck. PATIENTS AND METHODS: Between 2006 and 2011, 92 consecutive patients with LASCC of the head and neck were treated with RT and concomitant weekly cetuximab...
June 3, 2017: Targeted Oncology
https://www.readbyqxmd.com/read/28578404/a-simple-and-rapid-lc-ms-ms-method-for-therapeutic-drug-monitoring-of-cetuximab-a-gpco-unicancer-proof-of-concept-study-in-head-and-neck-cancer-patients
#12
François Becher, Joseph Ciccolini, Diane-Charlotte Imbs, Clémence Marin, Claire Fournel, Charlotte Dupuis, Nicolas Fakhry, Bertrand Pourroy, Aurélie Ghettas, Alain Pruvost, Christophe Junot, Florence Duffaud, Bruno Lacarelle, Sebastien Salas
Administration of first-in-class anti-EGFR monoclonal antibody cetuximab is contingent upon extensive pharmacogenomic testing. However in addition to tumor genomics, drug exposure levels could play a critical, yet largely underestimated role, because several reports have demonstrated that cetuximab pharmacokinetic parameters, in particular clearance values, were associated with survival in patients. Here, we have developed an original bioanalytical method based upon the use of LC-MS/MS technology and a simplified sample preparation procedure to assay cetuximab in plasma samples from patients, thus meeting the requirements of standard Therapeutic Drug Monitoring in routine clinical practice...
June 2, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28571578/immunotherapy-in-head-and-neck-cancer-aiming-at-extreme-precision
#13
Petr Szturz, Jan B Vermorken
BACKGROUND: Locoregionally advanced, recurrent, and metastatic squamous cell carcinomas of the head and neck (SCCHN) remain difficult to treat disease entities, in which systemic treatment often forms an integral part of their management. Immunotherapy is based on functional restoration of the host immune system, helping to counteract various tumour evasion strategies. Broadly, immunotherapeutic approaches encompass tumour-specific antibodies, cancer vaccines, cytokines, adoptive T-cell transfer, and immune-modulating agents...
June 2, 2017: BMC Medicine
https://www.readbyqxmd.com/read/28560858/basal-subtype-is-predictive-for-response-to-cetuximab-treatment-in-patient-derived-xenografts-of-squamous-cell-head-and-neck-cancer
#14
Konrad Klinghammer, Raik Otto, Jan-Dirk Raguse, Andreas E Albers, Ingeborg Tinhofer, Iduna Fichtner, Ulf Leser, Ulrich Keilholz, Jens Hoffmann
Cetuximab is the single targeted therapy approved for the treatment of head and neck cancer (HNSCC). Predictive biomarkers have not been established and patient stratification based on molecular tumor profiles has not been possible. Since EGFR pathway activation is pronounced in basal subtype, we hypothesized this activation could be a predictive signature for an EGFR directed treatment. From our patient-derived xenograft platform of HNSCC, 28 models were subjected to Affymetrix gene expression studies on HG U133+ 2...
May 30, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28559019/il6-is-associated-with-response-to-dasatinib-and-cetuximab-phase-ii-clinical-trial-with-mechanistic-correlatives-in-cetuximab-resistant-head-and-neck-cancer
#15
L P Stabile, A M Egloff, M K Gibson, W E Gooding, J Ohr, P Zhou, N J Rothenberger, L Wang, J L Geiger, J T Flaherty, J R Grandis, J E Bauman
OBJECTIVE: Src family kinase (SFK) activation circumvents epidermal growth factor receptor (EGFR) targeting in head and neck squamous cell carcinoma (HNSCC); dual SFK-EGFR targeting could overcome cetuximab resistance. PATIENTS AND METHODS: We conducted a Simon two-stage, phase II trial of the SFK inhibitor, dasatinib, and cetuximab in biomarker-unselected patients with cetuximab-resistant, recurrent/metastatic HNSCC. Pre- and post-treatment serum levels of interleukin-6 (IL6) were measured by ELISA...
June 2017: Oral Oncology
https://www.readbyqxmd.com/read/28559018/outcome-of-recurrent-and-metastatic-head-and-neck-squamous-cell-cancer-patients-after-first-line-platinum-and-cetuximab-therapy
#16
Marco Siano, Gabriele Infante, Carlo Resteghini, Maria Chiara Cau, Salvatore Alfieri, Cristiana Bergamini, Roberta Granata, Rosalba Miceli, Laura Locati, Lisa Licitra, Paolo Bossi
OBJECTIVES: Second-line chemotherapy in recurrent and/or metastatic head and neck cancer (r/mHNSCC) patients showed dismal results with limited tumor response and reduced life expectancy. Outside of clinical trials, data on efficacy of second line treatment after first line anti-EGFR-AB combination therapy are not available. MATERIAL AND METHODS: Data regarding r/mHNSCC consecutive pts treated with cetuximab and platinum from 2009 to 2014 at our center were retrospectively collected...
June 2017: Oral Oncology
https://www.readbyqxmd.com/read/28557105/major-response-to-pembrolizumab-in-two-patients-with-locally-advanced-cutaneous-squamous-cell-carcinoma
#17
E Degache, J Crochet, N Simon, M Tardieu, S Trabelsi, M Moncourier, I Templier, L Foroni, A Lemoigne, N Pinel, H Gil, L Bouillet, M T Leccia, J Charles
Cutaneous squamous cell carcinomas (CSCC) are one of the most frequent types of cancer, with rising incidence rates(1). While the majority are cured with surgery, some CSCC are associated with significant morbidity and mortality due to their local extension and metastatic potential. The recommended treatment for these advanced stages includes radiotherapy, conventional chemotherapy, or cetuximab, which tends to yield modest responses and a high prevalence of toxic effects(2). Anti- Programmed Death-1 (PD-1) therapies recently showed their efficacy in several types of tumour, especially in patients with recurrent or metastatic head and neck squamous cell carcinomas that has continued to progress despite standard-of-care treatment, suggesting the potentical efficacy of anti-PD1 in CSCC (3,4)...
May 30, 2017: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/28526718/p16-hpv-and-cetuximab-what-is-the-evidence
#18
REVIEW
James A Bonner, Ricard Mesia, Jordi Giralt, Amanda Psyrri, Ulrich Keilholz, David I Rosenthal, Frank Beier, Jeltje Schulten, Jan B Vermorken
Squamous cell carcinoma of the head and neck (SCCHN) is the sixth most common cancer worldwide. It has recently been appreciated that human papillomavirus (HPV) status (or p16 status, which is a frequently used surrogate for HPV status) is prognostic for oropharyngeal SCCHN. Here, we review and contextualize existing p16 and HPV data, focusing on the cetuximab registration trials in previously untreated, locoregionally advanced, nonmetastatic SCCHN (LA SCCHN) and in recurrent and/or metastatic SCCHN (R/M SCCHN): the IMCL-9815 and EXTREME clinical trials, respectively...
July 2017: Oncologist
https://www.readbyqxmd.com/read/28522603/smad4-loss-is-associated-with-cetuximab-resistance-and-induction-of-mapk-jnk-activation-in-head-and-neck-cancer-cells
#19
Hiroyuki Ozawa, Ruchira S Ranaweera, Evgeny Izumchenko, Eugene Makarev, Alex Zhavoronkov, Elana J Fertig, Jason D Howard, Ana Markovic, Atul Bedi, Rajani Ravi, Jimena Perez, Quynh-Thu Le, Christina S Kong, Richard C Jordan, Hao Wang, Hyunseok Kang, Harry Quon, David Sidransky, Christine H Chung
Purpose: We previously demonstrated an association between decreased SMAD4 expression and cetuximab resistance in head and neck squamous cell carcinoma (HNSCC). The purpose of this study was to further elucidate the clinical relevance of SMAD4 loss in HNSCC.Experimental Design: SMAD4 expression was assessed by IHC in 130 newly diagnosed and 43 patients with recurrent HNSCC. Correlative statistical analysis with clinicopathologic data was also performed. OncoFinder, a bioinformatics tool, was used to analyze molecular signaling in TCGA tumors with low or high SMAD4 mRNA levels...
May 18, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28511189/the-role-of-audiometry-prior-to-high-dose-cisplatin-in-patients-with-head-and-neck-cancer
#20
Miguel Caballero, Paula Mackers, Oscar Reig, Elvira Buxo, Pilar Navarrete, Jose L Blanch, Juan J Grau
OBJECTIVES: To analyze the role of audiometry in considering change to a less ototoxic treatment in head and neck cancer (HNC) patients. METHODS: Consecutive patients prescribed high-dose cisplatin (100 mg/m2) between January 2013 and February 2015 were enrolled. Audiometry was performed at baseline and before cisplatin. Change to a less ototoxic agent or reduced cisplatin dose was considered with audiometric decreases >25 dB. RESULTS: A total of 103 patients were included; the median age of the patients was 59 years (range 18-75)...
May 17, 2017: Oncology
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