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cetuximab head and neck cancers

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https://www.readbyqxmd.com/read/28422758/first-in-human-trial-of-multikinase-vegf-inhibitor-regorafenib-and-anti-egfr-antibody-cetuximab-in-advanced-cancer-patients
#1
Vivek Subbiah, Muhammad Rizwan Khawaja, David S Hong, Behrang Amini, Jiang Yungfang, Hui Liu, Adrienne Johnson, Alexa B Schrock, Siraj M Ali, James X Sun, David Fabrizio, Sarina Piha-Paul, Siqing Fu, Apostolia M Tsimberidou, Aung Naing, Filip Janku, Daniel D Karp, Michael Overman, Cathy Eng, Scott Kopetz, Funda Meric-Bernstam, Gerald S Falchook
BACKGROUND: The combination of multikinase VEGF inhibitor regorafenib and anti-EGFR antibody cetuximab overcomes intrinsic and acquired resistance in both EGFR-sensitive and EGFR-resistant preclinical models of colorectal cancer (CRC). METHODS: Utilizing a standard 3+3 design, a phase I study was designed to determine safety, maximum tolerated dose (MTD), and dose-limiting toxicities (DLTs) of the regorafenib plus cetuximab combination among patients with advanced cancer including CRC...
April 20, 2017: JCI Insight
https://www.readbyqxmd.com/read/28413788/a-tertiary-care-experience-with-paclitaxel-and-cetuximab-as-palliative-chemotherapy-in-platinum-sensitive-and-nonsensitive-in-head-and-neck-cancers
#2
Vanita Noronha, Vijay M Patil, Amit Joshi, Atanu Bhattacharjee, Davinder Paul, Sachin Dhumal, Shashikant Juvekar, Supreeta Arya, Kumar Prabhash
BACKGROUND: The combination of paclitaxel and cetuximab (PaCe) has led to an encouraging response rate in Phase 2 setting with limited toxicity. The aim of our study was to assess the efficacy of this regimen in our setting in platinum sensitive and nonsensitive patients. METHODS: This was a retrospective analysis of head and neck cancer patients treated with weekly PaCe as palliative chemotherapy between May 2010 and August 2014. The standard schedule of cetuximab along with 80 mg/m(2) of weekly paclitaxel was administered till either disease progression or withdrawal of patient's consent...
January 2017: South Asian Journal of Cancer
https://www.readbyqxmd.com/read/28408386/increased-pd-1-and-tim-3-tils-during-cetuximab-therapy-inversely-correlates-with-response-in-head-and-neck-cancer-patients
#3
Hyun-Bae Jie, Raghvendra M Srivastava, Athanassios Argiris, Julie E Bauman, Lawrence P Kane, Robert L Ferris
Despite emerging appreciation for the important role of immune checkpoint receptors in regulating the effector functions of T cells, it is unknown whether their expression is involved in determining the clinical outcome in response to cetuximab therapy. We examined the expression patterns of immune checkpoint receptors (including PD-1, CTLA-4, and TIM-3) and cytolytic molecules (including granzyme B and perforin) of CD8+ tumorinfiltrating lymphocytes (TILs) and compared them to those of peripheral blood T lymphocytes (PBLs) in patients with head and neck cancer (HNSCC) during cetuximab therapy...
April 13, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28404956/cabazitaxel-in-recurrent-metastatic-squamous-cell-carcinoma-of-the-head-and-neck-phase-ii-unicancer-trial-orl03
#4
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...
March 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28382569/targeted-therapy-in-head-and-neck-cancer-an-update-on-current-clinical-developments-in-epidermal-growth-factor-receptor-targeted-therapy-and-immunotherapies
#5
REVIEW
Jonathan Moreira, Alexander Tobias, Michael P O'Brien, Mark Agulnik
Most patients diagnosed with head and neck squamous cell carcinoma (HNSCC) will present with locally advanced disease, requiring multimodality therapy. Despite this curative approach, a significant subset of these patients will develop locoregional failure and/or distant metastases. Despite significant progress in the treatment and subsequent prognosis of locally advanced HNSCC, the prognosis of those patients with recurrent and/or metastatic (R/M) HNSCC is poor, with short-lived responses to palliative chemotherapy and few therapeutic agents available...
April 5, 2017: Drugs
https://www.readbyqxmd.com/read/28376866/systemic-therapy-in-the-curative-treatment-of-head-and-neck-squamous-cell-cancer-a-systematic-review
#6
REVIEW
Eric Winquist, Chika Agbassi, Brandon M Meyers, John Yoo, Kelvin K W Chan
OBJECTIVE: To review the available evidence and make recommendations regarding use of systemically administered drugs in combination or in sequence with radiation (RT) and/or surgery for cure and/or organ preservation in patients with locally advanced nonmetastatic (Stage III to IVB) squamous cell carcinoma of the head and neck (LASCCHN). METHOD: Recognizing the Meta-analysis of Chemotherapy in Head and Neck Cancer (MACH-NC) group reports have de facto guided practice since 2000, we searched for systematic reviews in the MEDLINE, EMBASE and Cochrane Database of Systematic Reviews published from January 2000 to February 2015 in reference to 4 research questions...
April 4, 2017: Journal of Otolaryngology—Head & Neck Surgery
https://www.readbyqxmd.com/read/28366573/patterns-of-care-for-elderly-patients-with-locally-advanced-head-and-neck-cancer
#7
Jesus E Juarez, Jehee Choi, Maie St John, Elliot Abemayor, Mindi TenNapel, Allen M Chen
PURPOSE: To compare patterns of care for elderly patients aged ≥70 years with locally advanced head and neck cancer versus those of younger patients treated for the same disease. METHODS AND MATERIALS: The medical records of 421 consecutive patients over the age of 50 years treated at a single institution between April 2011 and June 2016 for stage III/IV squamous cell carcinoma of the head and neck were reviewed. The primary treatment approach was compared using a t test statistic among 3 age cohorts: 50 to 59 years (118 patients); 60 to 69 years (152 patients); and 70 years and older (151 patients)...
January 29, 2017: International Journal of Radiation Oncology, Biology, Physics
https://www.readbyqxmd.com/read/28328302/pembrolizumab-for-platinum-and-cetuximab-refractory-head-and-neck-cancer-results-from-a-single-arm-phase-ii-study
#8
Joshua Bauml, Tanguy Y Seiwert, David G Pfister, Francis Worden, Stephen V Liu, Jill Gilbert, Nabil F Saba, Jared Weiss, Lori Wirth, Ammar Sukari, Hyunseok Kang, Michael K Gibson, Erminia Massarelli, Steven Powell, Amy Meister, Xinxin Shu, Jonathan D Cheng, Robert Haddad
Purpose There are no approved treatments for recurrent/metastatic head and neck squamous cell carcinoma refractory to platinum and cetuximab. In the single-arm, phase II KEYNOTE-055 study, we evaluated pembrolizumab, an anti-programmed death 1 receptor antibody, in this platinum- and cetuximab-pretreated population with poor prognosis. Methods Eligibility stipulated disease progression within 6 months of platinum and cetuximab treatment. Patients received pembrolizumab 200 mg every 3 weeks. Imaging was performed every 6 to 9 weeks...
March 22, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28325607/japanese-clinical-practice-guideline-for-head-and-neck-cancer
#9
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...
March 18, 2017: Auris, Nasus, Larynx
https://www.readbyqxmd.com/read/28247918/management-of-radiodermatitis-associated-with-cetuximab-in-squamous-cell-carcinomas-of-the-head-and-neck
#10
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/28237712/the-efficiency-and-adverse-events-of-radiotherapy-with-cetuximab-for-japanese-head-and-neck-cancer-patients
#11
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/28229341/assessment-of-cetuximab-induced-infusion-reactions-and-administration-rechallenge-at-an-academic-medical-center
#12
Ellen Burke, Michelle Rockey, Dennis Grauer, Dave Henry, Prakash Neupane
Cetuximab is approved for treatment of squamous cell carcinoma of the head and neck (SCCHN). Cetuximab is generally well tolerated, but does carry a black box warning for infusion reactions (IRs). Incidence of IR in clinical trials was 15-20% for all grades and 3-5% for grades III-IV. Retrospective studies reported a higher incidence of all grade IRs and grades III-IV IR in areas of the Southeastern United States. Information regarding rechallenge doses after an IR has not been well described. At our institution, we frequently rechallenge on the same day after an initial IR...
April 2017: Medical Oncology
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
#13
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/28196873/lymphotoxin-beta-interacts-with-methylated-egfr-to-mediate-acquired-resistance-to-cetuximab-in-head-and-neck-cancer
#14
Dennis Shin-Shian Hsu, Wei-Lun Hwang, Chiou-Hwa Yuh, Chen-Hsi Chu, Yang-Hui Ho, Pon-Bo Chen, Han-Syuan Lin, Hua-Kuo Lin, Shih-Pei Wu, Chih-Yi Lin, Wen-Hao Hsu, Hsin-Yi Lan, Hsiao-Jung Wang, Shyh-Kuan Tai, Mien-Chie Hung, Muh-Hwa Yang
PURPOSE: In head and neck squamous cell carcinoma (HNSCC), the incidence of RAS mutation, which is the major cause of cetuximab resistance, is relatively rare compared with the other types of cancers, and the mechanism mediating acquired resistance is unclear compared with the driver gene mutation-mediated de novo resistance. Here we investigated the driver gene mutation-independent mechanism for cetuximab resistance in HNSCC. EXPERIMENTAL DESIGN: We used the in vitro-selected and in vivo-selected cetuximab-resistant sublines of HNSCC cell lines for investigating the mechanism of acquired resistance to cetuximab...
February 14, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28188964/predictors-of-distant-metastasis-in-human-papillomavirus-associated-oropharyngeal-cancer
#15
Michael A Weller, Matthew C Ward, Camille Berriochoa, Chandana A Reddy, Samuel Trosman, John F Greskovich, Tobenna I Nwizu, Brian B Burkey, David J Adelstein, Shlomo A Koyfman
BACKGROUND: Human papillomavirus (HPV)-positive oropharyngeal cancer is associated with favorable outcomes, prompting investigations into treatment deintensification. The purpose of this study was for us to present the predictors of distant metastases in patients with HPV-positive oropharyngeal cancer treated with cisplatin-based chemoradiotherapy (CRT) or cetuximab-based bioradiotherapy (bio-RT). METHODS: In patients with stage III to IVb HPV-positive oropharyngeal cancer, the Kaplan-Meier analysis was used to calculate distant metastases rates...
February 11, 2017: Head & Neck
https://www.readbyqxmd.com/read/28177558/tmem16a-ano1-suppression-improves-response-to-antibody-mediated-targeted-therapy-of-egfr-and-her2-erbb2
#16
Sucheta Kulkarni, Anke Bill, Neal R Godse, Nayel I Khan, Jason I Kass, Kevin Steehler, Carolyn Kemp, Kara Davis, Carol A Bertrand, Avani R Vyas, Douglas E Holt, Jennifer R Grandis, L Alex Gaither, Umamaheswar Duvvuri
TMEM16A, a Ca(2+) -activated Cl(-) channel, contributes to tumor growth in breast cancer and head and neck squamous cell carcinoma (HNSCC). Here, we investigated whether TMEM16A influences the response to EGFR/HER family-targeting biological therapies. Inhibition of TMEM16A Cl(-) channel activity in breast cancer cells with HER2 amplification induced a loss of viability. Cells resistant to trastuzumab, a monoclonal antibody targeting HER2, showed an increase in TMEM16A expression and heightened sensitivity to Cl(-) channel inhibition...
February 8, 2017: Genes, Chromosomes & Cancer
https://www.readbyqxmd.com/read/28166090/chemotherapy-for-recurrent-metastatic-head-and-neck-cancers
#17
Andy Karabajakian, Philippe Toussaint, Eve-Marie Neidhardt, Valérie Paulus, Pierre Saintigny, Jérôme Fayette
Chemotherapy is the only option of treatment for most patients presenting with a recurrent and/or metastatic head and neck squamous cell carcinoma. The triple association of cisplatin, 5-fluorouracile, and cetuximab is still the current standard for fit patients. Other schemes are currently being compared with this protocol in ongoing trials and the association of cisplatin, docetaxel, and cetuximab appears to be the most efficient. The human papilloma virus is very likely a favorable prognostic factor. Immunotherapy with nivolumab or pembrolizumab is now a new standard of treatment in second line after yielding an improvement in overall survival, but predictive markers of efficacy are needed to refine the selection of patients...
April 2017: Anti-cancer Drugs
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
#18
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 which 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 HPV positive and HPV negative HNSCC cell lines...
January 30, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28134662/chemotherapy-for-localized-head-and-neck-squamous-cell-cancers
#19
Andy Karabajakian, Philippe Toussaint, Eve-Marie Neidhardt, Valérie Paulus, Pierre Saintigny, Jérôme Fayette
Concomitant chemotherapy with cisplatin (100 mg/m every 3 weeks) improves outcome for high-risk patients in the postoperative setting and for inoperable disease. Toxicity is increased. Other schemes of potentiation are sometimes used to reduce toxicity, but efficiency is diminished. Cetuximab also improves outcome, but there has been no direct comparison with cisplatin. Immunotherapy is currently being evaluated in association with radiation therapy. Trials are ongoing to evaluate the impact of de-escalation for human papillomavirus-positive patients...
April 2017: Anti-cancer Drugs
https://www.readbyqxmd.com/read/28125819/advanced-squamous-cell-carcinoma-of-the-head-and-neck-the-current-role-of-cetuximab
#20
Martín Granados-García, José Luis Aguilar-Ponce, Federico Maldonado-Magos, Jaime G De la Garza-Salazar
We review clinical trials of squamous cell carcinoma of the head and neck (SCCHN) to address the current and potential uses of cetuximab (CTX). PubMed was reviewed to identify papers published between 2010 and 2016. The search terms used were "cetuximab" and "head and neck cancer." A total of 634 articles were identified. Phase II or III studies with CTX in patients with advanced SCCHN without treatment or with recurrent/metastatic tumors were selected. Forty-six registries were obtained. Information was critically reviewed and relevant information presented...
2016: ORL; Journal for Oto-rhino-laryngology and its related Specialties
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