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cetuximab AND radiotherapy

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https://www.readbyqxmd.com/read/28598813/identification-of-a-novel-atm-inhibitor-with-cancer-cell-specific-radiosensitization-activity
#1
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
#2
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...
June 8, 2017: Cancer Chemotherapy and Pharmacology
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
#3
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/28577306/cetuximab-or-nimotuzumab-plus-intensity-modulated-radiotherapy-versus-cisplatin-plus-intensity-modulated-radiotherapy-for-stage-ii-ivb-nasopharyngeal-carcinoma
#4
Rui You, Rui Sun, Yi-Jun Hua, Chao-Feng Li, Ji-Bin Li, Xiong Zou, Qi Yang, You-Ping Liu, Yi-Nuan Zhang, Tao Yu, Jing-Yu Cao, Meng-Xia Zhang, Rou Jiang, Hao-Yuan Mo, Ling Guo, Ka-Jia Cao, Ai-Hua Lin, Chao-Nan Qian, Ying Sun, Jun Ma, Ming-Yuan Chen
To compare intensity-modulated radiotherapy (IMRT) with cisplatin (CDDP) versus cetuximab (CTX) and nimotuzumab (NTZ) for Stage II-IVb Nasopharyngeal Carcinoma (NPC). A total of 1,837 patients with stage II - IVb NPC who received IMRT plus CTX or NTZ, or CDDP between January 2009 and December 2013 were included in the current analysis. Using propensity scores to adjust for potential prognostic factors, a well-balanced cohort of 715 patients was created by matching each patient who underwent IMRT plus concomitant NTZ/CTX with four patients who underwent IMRT plus concomitant CDDP (1:4)...
June 2, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28557105/major-response-to-pembrolizumab-in-two-patients-with-locally-advanced-cutaneous-squamous-cell-carcinoma
#5
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/28535302/inhibition-of-n-acetylglucosaminyltransferase-v-enhances-the-cetuximab-induced-radiosensitivity-of-nasopharyngeal-carcinoma-cells-likely-through-egfr-n-glycan-alterations
#6
Xiaomin Huang, Ting Liu, Qiongyao Wang, Weiliang Zhu, Hui Meng, Linlang Guo, Ting Wei, Jian Zhang
N-acetylglucosaminyltransferase V (GnT-V), an enzyme that catalyses the formation of the N-linked β-1-6 branching of oligosaccharides, is related to the radiosensitivity of nasopharyngeal carcinoma (NPC). Cetuximab (C225) is an epidermal growth factor receptor (EGFR) inhibitor used as a radiosensitizer in the treatment of NPC. In this study, we used GnT-V as a molecular target to further sensitize cetuximab-treated NPC cells to radiation. The results from two NPC cell lines (CNE1 and CNE2) revealed that the silencing of GnT-V enhanced cetuximab-induced radiosensitivity by decreasing the β-1-6 branching of oligosaccharides on the EGFR...
May 23, 2017: Glycobiology
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
#7
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/28453615/do-patient-access-schemes-for-high-cost-cancer-drugs-deliver-value-to-society-lessons-from-the-nhs-cancer-drugs-fund
#8
A Aggarwal, T Fojo, C Chamberlain, C Davis, R Sullivan
Background: The NHS Cancer Drugs Fund (CDF) was established in 2010 to reduce delays and improve access to cancer drugs, including those that had been previously appraised but not approved by NICE (National Institute for Health and Care Excellence). After 1.3 billion GBP expenditure, a UK parliamentary review in 2016 rationalized the CDF back into NICE. Methods: This paper analyses the potential value delivered by the CDF according to six value criteria. This includes validated clinical benefits scales, cost-effectiveness criteria as defined by NICE and an assessment of real-world data...
April 27, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28382396/retrospective-evaluation-of-concomitant-cetuximab-and-radiotherapy-tolerance-for-locoregional-advanced-head-and-neck-squamous-cell-carcinoma-treatment-in-patients-unfit-for-platinum-based-chemotherapy
#9
Audrey Rambeau, Radj Gervais, Dominique De Raucourt, Emmanuel Babin, Audrey Emmanuelle Dugué, Carmen Florescu, David Blanchard, Bernard Gery
Radiotherapy associated with cetuximab (Cet-RT) is an alternative treatment to platinum-based chemoradiotherapy in locally advanced head and neck carcinoma (LAHNC). Reviews suggest that the use of cetuximab is associated with poorer tolerance in patients unfit for chemotherapy than in pivotal trial. We retrospectively studied patients first treated by Cet-RT for LAHNC presenting contraindications to chemoradiotherapy. Objectives were treated population description, acute tolerance, progression-free survival (PFS), overall survival (OS), and 3-month clinical response...
April 5, 2017: European Archives of Oto-rhino-laryngology
https://www.readbyqxmd.com/read/28356978/reproducibility-of-the-egfr-immunohistochemistry-scores-for-tumor-samples-from-patients-with-advanced-non-small-cell-lung-cancer
#10
Alejandro Avilés-Salas, Saé Muñiz-Hernández, Héctor Aquiles Maldonado-Martínez, José G Chanona-Vilchis, Laura-Alejandra Ramírez-Tirado, Norma HernáNdez-Pedro, Rita Dorantes-Heredia, José Manuel RuíZ-Morales, Daniel Motola-Kuba, Oscar Arrieta
Epidermal growth factor receptor (EGFR) is overexpressed in >60% of non-small cell lung cancer (NSCLC) cases. In combination with radiotherapy or chemotherapy, first-line treatments with antibodies against EGFR, including cetuximab and necitumumab, have demonstrated benefits by increasing overall survival (OS), particularly in patients who overexpress EGFR. The present study evaluated the interobserver agreement among three senior pathologists, who were blinded to the clinical outcomes and assessed tumor samples from 85 patients with NSCLC using the H-score method...
February 2017: Oncology Letters
https://www.readbyqxmd.com/read/28325607/japanese-clinical-practice-guideline-for-head-and-neck-cancer
#11
REVIEW
Ken-Ichi Nibu, Ryuichi Hayashi, Takahiro Asakage, Hiroya Ojiri, Yoshihiro Kimata, Takeshi Kodaira, Toshitaka Nagao, Torahiko Nakashima, Takashi Fujii, Hirofumi Fujii, Akihiro Homma, Kazuto Matsuura, Nobuya Monden, Takeshi Beppu, Nobuhiro Hanai, Tadaaki Kirita, Yuzuru Kamei, Naoki Otsuki, Naomi Kiyota, Sadamoto Zenda, Ken Omura, Koichi Omori, Tetsuo Akimoto, Kazuyoshi Kawabata, Seiji Kishimoto, Hiroya Kitano, Iwai Tohnai, Takashi Nakatsuka
OBJECTIVE: The first revision of "Japanese Clinical Practice Guideline for Head and Neck Cancer" was made in 2013 by the clinical practice guideline committee of Japan Society for Head and Neck Cancer, in response to the revision of the TNM classification. METHODS: 34 CQs (Clinical Questions) were newly adopted to describe the diagnosis and treatment methods currently considered most appropriate, and offered recommendation grade made by the consensus of the committee...
August 2017: Auris, Nasus, Larynx
https://www.readbyqxmd.com/read/28259294/understanding-c-met-signalling-in-squamous-cell-carcinoma-of-the-head-neck
#12
REVIEW
P Szturz, E Raymond, C Abitbol, S Albert, A de Gramont, S Faivre
c-MET is a membrane spanning receptor tyrosine kinase for hepatocyte growth factor (HGF) also termed scatter factor. Transmitting signals from mesenchymal to epithelial cells, the HGF/c-MET axis mediates a range of biological processes that stimulate proliferation, motility, invasiveness, morphogenesis, apoptosis, and angiogenesis. Aberrant c-MET signal transduction favours tumorigenesis with the acquisition of invasive and metastatic phenotypes. Biological functions of c-MET may strongly vary according to microenvironmental changes, which occur at different stages of tumorigenesis and include also HGF/c-MET activation in stromal cells...
March 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28247918/management-of-radiodermatitis-associated-with-cetuximab-in-squamous-cell-carcinomas-of-the-head-and-neck
#13
REVIEW
Michelle Villavicencio, Martin Granados-García, Esther Vilajosana, Judith Domínguez-Cherit
The objective of this review is to report to the medical community the most recent knowledge on prevention and management of dermatitis with the use of cetuximab simultaneously with radiotherapy in the treatment of squamous cell carcinomas of the head and neck. A review was conducted in PubMed of English language publications between 2010 and 2015. The search employed the terms 'skin toxicity', 'radiodermatitis', 'cetuximab', 'radiotherapy', and 'head and neck cancer'. Data related to the classification and management of dermatitis, associated with cetuximab with concomitant radiotherapy (n = 22), were critically reviewed...
March 1, 2017: International Journal of Dermatology
https://www.readbyqxmd.com/read/28237868/a-pet-based-nomogram-for-oropharyngeal-cancers
#14
J Castelli, A Depeursinge, V Ndoh, J O Prior, M Ozsahin, A Devillers, H Bouchaab, E Chajon, R de Crevoisier, N Scher, F Jegoux, B Laguerre, B De Bari, J Bourhis
PURPOSE: In the context of locally advanced oropharyngeal cancer (LAOC) treated with definitive radiotherapy (RT) (combined with chemotherapy or cetuximab), the aims of this study were: (1) to identify PET-FDG parameters correlated with overall survival (OS) from a first cohort of patients; then (2) to compute a prognostic score; and (3) finally to validate this scoring system in a second independent cohort of patients. MATERIALS AND METHODS: A total of 76 consecutive patients (training cohort from Rennes) treated with chemoradiotherapy or RT with cetuximab for LAOC were used to build a predictive model of locoregional control (LRC) and OS based on PET-FDG parameters...
February 23, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28237712/the-efficiency-and-adverse-events-of-radiotherapy-with-cetuximab-for-japanese-head-and-neck-cancer-patients
#15
Kazuhiro Hirasawa, Isaku Okamoto, Ray Motohashi, Hiroki Sato, Soichiro Takase, Ayumi Agata, Atsuo Takeda, Kiyoaki Tsukahara
OBJECTIVES: Radiotherapy with cisplatin (Chemoradiotherapy, CRT) has long been one of the standard treatments for head and neck squamous cell cancer (HNSCC). Approval of cetuximab for the treatment of HNSCC has made radiotherapy with cetuximab (Bioradiotherapy, BRT) a new treatment option for HNSCC. Reports of BRT in the Japanese written in English up to now is only the phase II study, though it includes only 22 patients. Also on the nature of the clinical Phase II trial, sampling bias of cases may exist...
February 22, 2017: Auris, Nasus, Larynx
https://www.readbyqxmd.com/read/28198410/evaluation-of-the-immunological-profile-of-antibody-functionalized-metal-filled-single-walled-carbon-nanocapsules-for-targeted-radiotherapy
#16
Aritz Perez Ruiz de Garibay, Cinzia Spinato, Rebecca Klippstein, Maxime Bourgognon, Markus Martincic, Elzbieta Pach, Belén Ballesteros, Cécilia Ménard-Moyon, Khuloud T Al-Jamal, Gerard Tobias, Alberto Bianco
This study investigates the immune responses induced by metal-filled single-walled carbon nanotubes (SWCNT) under in vitro, ex vivo and in vivo settings. Either empty amino-functionalized CNTs [SWCNT-NH2 (1)] or samarium chloride-filled amino-functionalized CNTs with [SmCl3@SWCNT-mAb (3)] or without [SmCl3@SWCNT-NH2 (2)] Cetuximab functionalization were tested. Conjugates were added to RAW 264.7 or PBMC cells in a range of 1 μg/ml to 100 μg/ml for 24 h. Cell viability and IL-6/TNFα production were determined by flow cytometry and ELISA...
February 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28197666/elevated-basal-antibody-dependent-cell-mediated-cytotoxicity-adcc-and-high-epidermal-growth-factor-receptor-egfr-expression-predict-favourable-outcome-in-patients-with-locally-advanced-head-and-neck-cancer-treated-with-cetuximab-and-radiotherapy
#17
Laura Lattanzio, Nerina Denaro, Daniela Vivenza, Chiara Varamo, Giuliana Strola, Mirella Fortunato, Emmanuel Chamorey, Alberto Comino, Martino Monteverde, Cristiana Lo Nigro, Gerard Milano, Marco Merlano
BACKGROUND: Antibody-dependent cell-mediated cytotoxicity (ADCC) may contribute to the antitumor activity of cetuximab. However, the extent of this contribution is unclear. In this study, we investigated the impact of baseline ADCC on the outcome of patients with locally advanced squamous cell carcinoma treated with cetuximab and radiotherapy. METHODS: We determined baseline ADCC in 28 patients treated with cetuximab and radiotherapy and in 15 patients treated with chemoradiation...
February 14, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28196063/long-term-results-and-recurrence-patterns-from-scope-1-a-phase-ii-iii-randomised-trial-of-definitive-chemoradiotherapy-cetuximab-in-oesophageal-cancer
#18
RANDOMIZED CONTROLLED TRIAL
T Crosby, C N Hurt, S Falk, S Gollins, J Staffurth, R Ray, J A Bridgewater, J I Geh, D Cunningham, J Blazeby, R Roy, T Maughan, G Griffiths, S Mukherjee
BACKGROUND: The SCOPE-1 study tested the role of adding cetuximab to conventional definitive chemoradiotherapy (dCRT), and demonstrated greater toxicity and worse survival outcomes. We present the long-term outcomes and patterns of recurrence. METHODS: SCOPE-1 was a phase II/III trial in which patients were randomised to cisplatin 60 mg m(-2) (day 1) and capecitabine 625 mg m(-2) bd (days 1-21) for four cycles +/- cetuximab 400 mg m(-2) day 1 then by 250 mg m(-2) weekly...
March 14, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28138221/immunotherapy-for-the-treatment-of-colorectal-tumors-focus-on-approved-and-in-clinical-trial-monoclonal-antibodies
#19
REVIEW
Alex Françoso, Patricia Ucelli Simioni
Colorectal cancer is considered a disease of the elderly population. Since the number of geriatric patients continues to rise, monoclonal antibody therapy is the most promising therapy in the recent research. Presently, the monoclonal antibodies most frequently used in the treatment of colorectal tumors are bevacizumab, cetuximab, panitumumab, and ramucirumab. Bevacizumab is a monoclonal antibody that acts on VEGF. Cetuximab and panitumumab act on EGFR. Ramucirumab binds directly to the ligand-binding pocket of VEGFR-2 to block the binding of VEGF-A, VEGF-C, and VEGF-D...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28138028/combining-chk1-2-inhibition-with-cetuximab-and-radiation-enhances-in-vitro-and-in-vivo-cytotoxicity-in-head-and-neck-squamous-cell-carcinoma
#20
Ling Zeng, Reena R Beggs, Tiffiny S Cooper, Alice N Weaver, Eddy S Yang
EGFR inhibition and radiotherapy are potent inducers of DNA damage. Checkpoint kinases 1 and 2 (Chk1/2) are critical regulators of the DNA-damage response, controlling cell-cycle checkpoints that may permit recovery from therapy-associated genomic stress. We hypothesized that Chk1/2 inhibition (CHKi) with prexasertib may enhance cytotoxicity from EGFR inhibition plus radiotherapy in head and neck squamous cell carcinoma (HNSCC). In this study, we found that the addition of CHKi to the EGFR inhibitor cetuximab with and without radiotherapy significantly decreased cell proliferation and survival fraction in human papillomavirus virus (HPV)-positive and HPV-negative HNSCC cell lines...
April 2017: Molecular Cancer Therapeutics
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