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https://www.readbyqxmd.com/read/28526718/p16-hpv-and-cetuximab-what-is-the-evidence
#1
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...
May 18, 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
#2
Hiroyuki Ozawa, Ruchira 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 K 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 immunohistochemistry in 130 newly diagnosed and 43 recurrent HNSCC patients. Correlative statistical analysis with clinicopathological 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
#3
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
https://www.readbyqxmd.com/read/28507280/molecular-dissection-of-effector-mechanisms-of-ras-mediated-resistance-to-anti-egfr-antibody-therapy
#4
Stefan Kasper, Henning Reis, Sophie Ziegler, Silke Nothdurft, Andre Mueller, Moritz Goetz, Marcel Wiesweg, Jeannette Phasue, Saskia Ting, Sarah Wieczorek, Anna Even, Karl Worm, Michael Pogorzelski, Sandra Breitenbuecher, Johannes Meiler, Andreas Paul, Tanja Trarbach, Kurt Werner Schmid, Frank Breitenbuecher, Martin Schuler
Monoclonal antibodies targeting the epidermal growth factor receptor (EGFR), cetuximab and panitumumab, are a mainstay of metastatic colorectal cancer (mCRC) treatment. However, a significant number of patients suffer from primary or acquired resistance. RAS mutations are negative predictors of clinical efficacy of anti-EGFR antibodies in patients with mCRC. Oncogenic RAS activates the MAPK and PI3K/AKT pathways, which are considered the main effectors of resistance. However, the relative impact of these pathways in RAS-mutant CRC is less defined...
April 26, 2017: Oncotarget
https://www.readbyqxmd.com/read/28500491/hyperfractionated-accelerated-radiation-therapy-plus-cetuximab-plus-cisplatin-chemotherapy-in-locally-advanced-inoperable-squamous-cell-carcinoma-of-the-head-and-neck-final-5%C3%A2-year-results-of-a-phase%C3%A2-ii-study
#5
Thomas Kuhnt, Andreas Schreiber, Anett Pirnasch, Matthias G Hautmann, Peter Hass, Frank P Sieker, Rita Engenhart-Cabillic, Michael Richter, Kathrin Dellas, Jürgen Dunst
BACKGROUND: Cetuximab (CET) is a potent inhibitor of the epidermal growth factor receptor and has been shown to have activity in squamous cell carcinoma of the head and neck (SCCHN). We conducted a single-arm phase II trial of a combination therapy comprising cisplatin (CIS), CET and hyperfractionated accelerated radiotherapy (HART). PATIENTS AND METHODS: Patients with UICC stage III or IVA/B, M0 SCCHN were enrolled and treated with an initial dose of CET (400 mg/m(2)) and then with a weekly dosage of 250 mg/m(2) during HART...
May 12, 2017: Strahlentherapie und Onkologie: Organ der Deutschen Röntgengesellschaft ... [et Al]
https://www.readbyqxmd.com/read/28497612/accurate-assessment-of-alpha-gal-syndrome-using-cetuximab-and-bovine-thyroglobulin-specific-ige
#6
Da Woon Sim, Jong Sun Lee, Kyung Hee Park, Kyoung Yong Jeong, Young-Min Ye, Jae-Hyun Lee, Jung-Won Park
SCOPE: IgE against galactose-α-1,3-galactose (α-Gal) cause alpha-gal syndrome. Bovine thyroglobulin (BTG) and cetuximab share this epitope. We aimed to determine the utility of specific IgE (sIgE) against cetuximab as compared to BTG for diagnosing alpha-gal syndrome. METHODS AND RESULTS: Twelve patients with alpha-gal syndrome, 11 patients with immediate beef or pork allergy, 18 asymptomatic individuals with meat sensitivity, and 10 non-atopic subjects were enrolled...
May 12, 2017: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/28497320/accelerating-drug-development-by-efficiently-using-emerging-pk-pd-data-from-an-adaptable-entry-into-human-trial-example-of-lumretuzumab
#7
Georgina Meneses-Lorente, Christine McIntyre, Joy C Hsu, Marlene Thomas, Wolfgang Jacob, Celine Adessi, Martin Weisser
PURPOSE: This study aimed at evaluating if pharmacokinetic and pharmacodynamic data from the first few patients treated with an investigational monoclonal antibody in a dose-escalation study can be used to guide the early initiation of potentially more efficacious combination regimens. METHODS: Emerging pharmacokinetic and pharmacodynamic data from the first nine patients treated with lumretuzumab (a glycoengineered anti-HER3 monoclonal antibody) monotherapy at doses from 100 to 400 mg q2w were used along with a pharmacokinetic model that incorporated target-mediated drug disposition to guide the selection of the starting dose for use in combination regimens...
June 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28494171/zinc-oxide-nanoparticles-antagonize-the-effect-of-cetuximab-on-head-and-neck-squamous-cell-carcinoma-in-vitro
#8
Thomas Gehrke, Agmal Scherzad, Pascal Ickrath, Philipp Schendzielorz, Rudolf Hagen, Norbert Kleinsasser, Stephan Hackenberg
Zinc oxide nanoparticles (ZnO-NPs) are being used in many cosmetic products and have been shown to induce tumor-selective cell death in human head and neck squamous cell carcinoma (HNSCC) in vitro. Cetuximab is a monoclonal antibody directed against the epidermal growth factor receptor (EGFR), whose effectiveness for HNSCC, alone or in combination with cytostatic drugs, has been demonstrated intensively in the last decades. Nanoparticles are known to interact with protein structures and thus may influence their functionality...
May 11, 2017: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/28493713/cetuximab-prevents-methotrexate-induced-cytotoxicity-in-vitro-through-epidermal-growth-factor-dependent-regulation-of-renal-drug-transporters
#9
Pedro Caetano-Pinto, Amer Jamalpoor, Janneke Ham, Anastasia Goumenou, Monique Mommersteeg, Dirk Pijnenburg, Rob Ruijtenbeek, Natalia Sánchez-Romero, Bertrand van Zelst, Sandra Heil, Jitske Jansen, Martijn J Wilmer, Carla M L van Herpen, Rosalinde Masereeuw
The combination of methotrexate with epidermal growth factor receptor (EGFR) recombinant antibody, cetuximab, is currently being investigated in treatment of head and neck carcinoma. As methotrexate is cleared by renal excretion, we studied the effect of cetuximab on renal methotrexate handling. We used human conditionally immortalized proximal tubule epithelial cells over-expressing either organic anion transporter 1 or 3 (ciPTEC-OAT1/ciPTEC-OAT3) to examine OAT1 and OAT3, and the efflux pumps breast cancer resistance protein (BCRP), multidrug resistance protein 4 (MRP4) and P-glycoprotein (P-gp) in methotrexate handling upon EGF and/or cetuximab treatment...
May 11, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28490940/systemic-therapy-in-the-curative-treatment-of-head-and-neck-squamous-cell-cancer-cancer-care-ontario-clinical-practice-guideline
#10
E Winquist, C Agbassi, B M Meyers, J Yoo, K K W Chan
OBJECTIVE: The aim of the present work was to make recommendations about the use of systemically administered drugs in combination or in sequence with radiation (rt) or surgery, or both, for cure or organ preservation, or both, in patients with locally advanced nonmetastatic (stages iii-ivb) squamous cell carcinoma of the head and neck (lascchn). METHODS: The Meta-analysis of Chemotherapy in Head and Neck Cancer (mach-nc) reports have, de facto, guided practice since 2000, and so we searched the literature for systematic reviews published from January 2000 to February 2015 in reference to five research questions...
April 2017: Current Oncology
https://www.readbyqxmd.com/read/28485336/efficacy-and-toxicity-of-cetuximab-with-chemotherapy-in-recurrent-and-metastatic-head-and-neck-cancer-a-prospective-observational-study
#11
S Tiwari, V Goel, M C John, N Patnaik, D C Doval
BACKGROUND: In squamous cell carcinoma of the head and neck (SCCHN), epidermal growth factor receptor is expressed at very high levels. Hence, we have done this study to assess the response and tolerability of cetuximab and platinum-based chemotherapy in recurrent and metastatic (R/M) head and neck squamous cell cancer (HNSCC) in view of paucity of data from the Indian subcontinent. MATERIALS AND METHODS: In this prospective study, patients of R/M SCCHN were randomly enrolled from September 2012 to April 2015...
October 2016: Indian Journal of Cancer
https://www.readbyqxmd.com/read/28485332/current-status-of-systemic-therapy-for-recurrent-and-or-metastatic-squamous-cell-carcinoma-of-the-head-and-neck
#12
REVIEW
L A Jacob, T Chaudhuri, K C Lakshmaiah, K G Babu, L Dasappa, McS Babu, A H Rudresha, K N Lokesh, L K Rajeev
Head and neck squamous cell carcinoma (HNSCC) is now the seventh most common cancer worldwide. The median overall survival for patients with recurrent and/or metastatic (R/M) HNSCC remains <1 year despite modern systemic chemotherapy and targeted agents. Palliative systemic therapy for patients with R/M HNSCC typically includes a platinum-based doublet, with an understanding that the increase in efficacy compared with single agents is primarily related to improved response rate, and not survival. Till date, the only systemic therapy regimen to demonstrate survival superiority over platinum-5-fluorouracil (5-FU) doublet is platinum, FU, and cetuximab...
October 2016: Indian Journal of Cancer
https://www.readbyqxmd.com/read/28483336/prospective-study-of-cetuximab-carboplatin-and-radiation-therapy-for-patients-with-locally-advanced-head-and-neck-squamous-cell-cancer-unfit-for-cisplatin
#13
June Corry, Mathias Bressel, Tsien Fua, Alan Herschtal, Benjamin Solomon, Sandro V Porceddu, Chris Wratten, Danny Rischin
PURPOSE: To report on the outcomes of a novel treatment regimen for patients with locally advanced head and neck squamous cell carcinoma who were fit for curative treatment but not fit for cisplatin. METHODS AND MATERIALS: Single-arm phase 1/2 study of previously untreated patients with biopsy-proven SCC of the oropharynx, larynx, or hypopharynx. The primary endpoint was feasibility of the regimen, defined as the proportion of patients successfully completing treatment...
February 24, 2017: International Journal of Radiation Oncology, Biology, Physics
https://www.readbyqxmd.com/read/28482611/cetuximab-conjugated-and-doxorubicin-loaded-silica-nanoparticles-for-tumor-targeting-and-tumor-microenvironment-responsive-binary-drug-delivery-of-liver-cancer-therapy
#14
Jia-Kang Wang, Yu-Ying Zhou, Shu-Jun Guo, Ya-Yu Wang, Chang-Jun Nie, Hai-Long Wang, Jia-Lang Wang, Ying Zhao, Xiao-Yan Li, Xiao-Jia Chen
In the present study, we successfully developed a preferable doxorubicin (Dox) loaded drug delivery system based on Cetuximab and silica nanoparticles (Cet-SLN/Dox). By employing the tumor homing property of Cetuximab and the drug-loading capability of silica nanoparticles, the prepared Cet-SLN/Dox was able to load Dox to achieve the co-delivery of two drugs (Cetuximab and Dox). In vitro analysis revealed that Cet-SLN/Dox was nano-sized particles with decent drug loading capabilities and smart drug release profile...
July 1, 2017: Materials Science & Engineering. C, Materials for Biological Applications
https://www.readbyqxmd.com/read/28473715/rationally-co-targeting-divergent-pathways-in-kras-wild-type-colorectal-cancers-by-canscript-technology-reveals-tumor-dependence-on-notch-and-erbb2
#15
Nilesh Brijwani, Misti Jain, Muthu Dhandapani, Farrah Zahed, Pragnashree Mukhopadhyay, Manjusha Biswas, Deepak Khatri, Vinod D Radhakrishna, Biswanath Majumder, Padhma Radhakrishnan, Saravanan Thiyagarajan
KRAS mutation status can distinguish between metastatic colorectal carcinoma (mCRC) patients who may benefit from therapies that target the epidermal growth factor receptor (EGFR), such as cetuximab. However, patients whose tumors harbor mutant KRAS (codons 12/13, 61 and 146) are often excluded from EGFR-targeted regimens, while other patients with wild type KRAS will sometimes respond favorably to these same drugs. These conflicting observations suggest that a more robust approach to individualize therapy may enable greater frequency of positive clinical outcome for mCRC patients...
May 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28471725/how-standard-is-second-line-cetuximab-in-recurrent-or-metastatic-head-and-neck-cancer-in-2017
#16
Petr Szturz, Tanguy Y Seiwert, Jan B Vermorken
No abstract text is available yet for this article.
May 4, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28468237/hypoxia-mediates-differential-response-to-anti-egfr-therapy-in-hnscc-cells
#17
Emilia Wiechec, Katharina Tiefenböck Hansson, Lisa Alexandersson, Jan-Ingvar Jönsson, Karin Roberg
Despite advances in the head and neck squamous cell carcinoma (HNSCC) treatment modalities, drug resistance and cancer recurrence are often reported. Hypoxia signaling through hypoxia-inducible factor 1 (HIF-1) promotes angiogenesis and metastasis by inducing epithelial-mesenchymal-transition (EMT). The aim of this study was to evaluate the impact of hypoxia on response to therapy as well as EMT and expression of stem cell markers in HNSCC cells. Five HNSCC cell lines (UT-SCC-2, UT-SCC-14, LK0412, LK0827, and LK0923) were selected for this study...
April 29, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28467975/adcc-responses-and-blocking-of-egfr-mediated-signaling-and-cell-growth-by-combining-the-anti-egfr-antibodies-imgatuzumab-and-cetuximab-in-nsclc-cells
#18
Arjan Kol, Anton Terwisscha van Scheltinga, Martin Pool, Christian Gerdes, Elisabeth de Vries, Steven de Jong
Imgatuzumab is a novel glycoengineered anti-epidermal growth factor receptor (EGFR) monoclonal antibody optimized to induce both antibody-dependent cellular cytotoxicity (ADCC) and EGFR signal transduction inhibition. We investigated anti-EGFR monoclonal antibodies imgatuzumab and cetuximab-induced internalization and membranous turnover of EGFR, and whether this affected imgatuzumab-mediated ADCC responses and growth inhibition of non-small cell lung cancer (NSCLC) cells.In a panel of wild-type EGFR expressing human NSCLC cell lines, membranous and total EGFR levels were downregulated more effectively by imgatuzumab when compared with cetuximab...
April 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28463756/impact-of-braf-and-ras-mutations-on-first-line-efficacy-of-folfiri-plus-cetuximab-versus-folfiri-plus-bevacizumab-analysis-of-the-fire-3-aio-krk-0306-study
#19
S Stintzing, L Miller-Phillips, D P Modest, L Fischer von Weikersthal, T Decker, A Kiani, U Vehling-Kaiser, S-E Al-Batran, T Heintges, C Kahl, G Seipelt, F Kullmann, M Stauch, W Scheithauer, S Held, M Moehler, A Jagenburg, T Kirchner, A Jung, V Heinemann
BACKGROUND: RAS and BRAF mutations have been identified as negative prognostic factors in metastatic colorectal cancer. Efficacy of 5-fluorouracil, leucovorin, irinotecan (FOLFIRI) plus bevacizumab in patients with RAS-mutant tumours needs to be further evaluated. Whether to treat patients with BRAF-mutant tumours with either bevacizumab or anti-epidermal growth factor receptor (EGFR) antibodies remains unclear. METHODS: Patients treated within the FIRE-3 trial were retrospectively tested for BRAF and RAS mutations using formalin fixated paraffin embedded (FFPE) tumour material applying pyrosequencing for KRAS and NRAS exon 2, 3 and 4 mutations as far as for BRAF mutations...
April 29, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28456898/predictive-value-of-early-skin-rash-in-cetuximab-based-therapy-of-advanced-biliary-tract-cancer
#20
Gábor Rubovszky, Barna Budai, Erna Ganofszky, Zsolt Horváth, Éva Juhos, Balázs Madaras, Tünde Nagy, Eszter Szabó, Tamás Pintér, Erika Tóth, Péter Nagy, István Láng, Erika Hitre
Randomized trials in advanced biliary tract cancer (BTC) did not show benefit of cetuximab addition over chemotherapy. This is probably due to the lack of predictive biomarkers. The aim of this study was to explore possible predictive factors. Between 2009 and 2014, 57 patients were treated in 3-week cycles with cetuximab (250 mg/m(2)/week, loading dose: 400 mg/m(2)), gemcitabine (1000 mg/m(2) on day 1 and 8), and capecitabine (1300 mg/m(2)/day on days 1-14). The objective response rate (ORR), progression-free (PFS) and overall survival (OS) and the adverse events (AEs) were evaluated...
April 29, 2017: Pathology Oncology Research: POR
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