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cetuximab head and neck cancers

Yoann Pointreau, Nicolas Azzopardi, David Ternant, Gilles Calais, Gilles Paintaud
BACKGROUND: A retrospective study was conducted to analyze interindividual variability of cetuximab pharmacokinetics and its influence on survival (Progression Free Survival - PFS and overall survival - OS) in a cohort of head and neck squamous cell carcinoma (HNSCC). METHODS: Thirty-four patients received cetuximab as an infusion loading dose of 400 mg/m followed by weekly infusions of 250 mg/m. Twenty-one patients had locally advanced HNSCC (LAHNSCC) and thirteen had metastatic/recurrent HNSCC (MHNSCC)...
July 4, 2016: Therapeutic Drug Monitoring
Ajay Gupta, Siddhartha Baxi, Christopher Hoyne
INTRODUCTION: Comprehensive oncology services have recently been introduced in the Northern Territory (NT) enabling delivery of concurrent chemo-radiotherapy (CCRT) in locally advanced head and neck squamous cell carcinoma (LAHNSC). The purpose of this study is to assess feasibility, compliance and toxicity of CCRT in remote Australia. METHODS: Chart review was conducted for all patients >18 years, with biopsy-proven LAHNSC, receiving curative intent CCRT between January 2010 and September 2012...
July 1, 2016: Journal of Medical Radiation Sciences
Caroline Brammer, Sundus Yahya, Dawn Dawson, Carol Glaister, Susan B Merrick
OBJECTIVES: The aim of this feasibility study is to define the resource effectiveness of Cetuximab versus cisplatin given concomitantly with radiotherapy for squamous cell carcinoma within a NHS clinical oncology unit. METHODS: 20 Patients with stage 3 or 4 head and neck squamous cell cancers were randomised to receive either Cetuximab with radiotherapy (ERT) or cisplatin with radiotherapy (CRT) concurrent with external beam radiotherapy 70 Gy in 35 fractions on a 1:1 basis over a 12-month duration...
October 13, 2016: British Journal of Radiology
Alexander T Falk, Christophe Hébert, Antoine Tran, Marie-Eve Chand, Axel Leysalle, Juliette Thariat, Olivier Dassonville, Gilles Poissonnet, Alexandre Bozec, Esma Saada, Fréderic Peyrade, Karen Benezery
Concomitant radiotherapy and cetuximab association has shown superiority to exclusive radiotherapy for head and neck cancers. Data on this association are scarce for the elderly population despite its rising incidence. A retrospective monocentric data collection was performed in the Antoine Lacassagne Cancer Center in France. Inclusion criteria were: age >70 years at time of diagnosis, histologically proven head and neck epidermoid carcinoma, treated with radiotherapy combined with cetuximab. Thirty-five patients were included between 2008 and 2012...
October 11, 2016: European Archives of Oto-rhino-laryngology
Minh Tam Truong, Qiang Zhang, David I Rosenthal, Marcie List, Rita Axelrod, Eric Sherman, Randal Weber, Phuc Felix Nguyen-Tân, Adel El-Naggar, André Konski, James Galvin, David Schwartz, Andy Trotti, Craig Silverman, Anurag Singh, Karen Godette, James A Bonner, Christopher U Jones, Adam S Garden, George Shenouda, Chance Matthiesen, Quynh-Thu Le, Deborah Bruner
PURPOSE: To analyze the quality of life (QOL) and performance status (PS) (secondary outcome) in patients with stage III to IV head and neck cancer (HNC) enrolled on a prospective randomized phase 3 trial comparing radiation-cisplatin without cetuximab (CIS) or with cetuximab (CET/CIS). The QOL hypothesis proposed a between-arm difference in Functional Assessment of Cancer Therapy-Head and Neck (FACT-HN) total score of ≥10% of the instrument range from baseline to 1 year. METHODS AND MATERIALS: Patients who gave consent to the QOL/PS study completed the FACT-HN, Performance Status Scale for HNC (PSS-HN), and EuroQol (EQ-5D) at baseline through to 5 years...
August 12, 2016: International Journal of Radiation Oncology, Biology, Physics
Gopal Iyer, James Price, Shay Bourgeois, Eric Armstrong, Shyhmin Huang, Paul M Harari
BACKGROUND: The epidermal growth factor receptor (EGFR) is frequently overexpressed in head and neck squamous cell carcinoma (HNSCC) and several other human cancers. Monoclonal antibodies, such as cetuximab that block EGFR signaling, have emerged as valuable molecular targeting agents in clinical cancer therapy. Prolonged exposure to cetuximab can result in cells acquiring resistance by a process that remains incompletely understood. METHODS: In this study, we analyzed the immediate early molecular response of cetuximab on physical interactions between EGFR and Insulin growth factor 1 like receptor (IGF-1R) in head and neck cancer cells that are resistant to cetuximab...
October 6, 2016: BMC Cancer
Jingtao Luo, Yun Hong, Yang Lu, Songbo Qiu, Bharat K R Chaganty, Lun Zhang, Xudong Wang, Qiang Li, Zhen Fan
Cetuximab inhibits HIF-1-regulated glycolysis in cancer cells, thereby reversing the Warburg effect and leading to inhibition of cancer cell metabolism. AMP-activated protein kinase (AMPK) is activated after cetuximab treatment, and a sustained AMPK activity is a mechanism contributing to cetuximab resistance. Here, we investigated how acetyl-CoA carboxylase (ACC), a downstream target of AMPK, rewires cancer metabolism in response to cetuximab treatment. We found that introduction of experimental ACC mutants lacking the AMPK phosphorylation sites (ACC1_S79A and ACC2_S212A) into head and neck squamous cell carcinoma (HNSCC) cells protected HNSCC cells from cetuximab-induced growth inhibition...
September 28, 2016: Cancer Letters
Ping Yu, Yibo Fan, Xiujuan Qu, Jingdong Zhang, Na Song, Jing Liu, Yunpeng Liu
PURPOSE: Cetuximab is a monoclonal antibody against epidermal growth factor receptor (EGFR) and is approved for clinical use in combination with chemotherapy in patients affected by colorectal cancer (CRC), non small cell lung cancer (NSCLC), and head and neck cancer. Compared with these cancers, gastric cancer is relatively resistant to cetuximab and its regulatory mechanism is still unclear. METHODS: In this study, we assessed whether the ubiquitin- proteasome pathway is involved in regulating cetuximab-induced cells apoptosis in MGC803 and BGC823 gastric cancer cell lines...
July 2016: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
Tomohiro Enokida, Shinya Suzuki, Tetsuro Wakasugi, Tomoko Yamazaki, Susumu Okano, Makoto Tahara
BACKGROUND: Hypomagnesemia is a common adverse event during cetuximab (Cmab) treatment. However, few reports have investigated the incidence and risk factors of hypomagnesemia in head and neck cancer patients treated with Cmab. METHODS: We retrospectively reviewed 131 head and neck cancer patients who received Cmab-containing therapy. Main eligibility criteria were ≥3 Cmab administrations, no prior EGFR-directed therapy, and no prophylactic Mg supplementation...
2016: Frontiers in Oncology
Patricia Guyot, A E Ades, Matthew Beasley, Béranger Lueza, Jean-Pierre Pignon, Nicky J Welton
BACKGROUND: Estimates of life expectancy are a key input to cost-effectiveness analysis (CEA) models for cancer treatments. Due to the limited follow-up in Randomized Controlled Trials (RCTs), parametric models are frequently used to extrapolate survival outcomes beyond the RCT period. However, different parametric models that fit the RCT data equally well may generate highly divergent predictions of treatment-related gain in life expectancy. Here, we investigate the use of information external to the RCT data to inform model choice and estimation of life expectancy...
September 28, 2016: Medical Decision Making: An International Journal of the Society for Medical Decision Making
B Dupont, D Mariotte, A E Dugué, B Clarisse, J-M Grellard, E Babin, B Chauffert, S Dakpé, C Moldovan, K Bouhier-Leporrier, J-M Reimund, F Di Fiore, S Zanetta, A Mailliez, P Do, A Peytier, M-P Galais, C Florescu, R Schott, B Le Mauff, R Gervais
AIM: Cetuximab is an anti-EGFR antibody used for the treatment of metastatic colorectal cancer and head and neck cancer. Hypersensitivity reactions (HSR) are associated with cetuximab use. The aim of the study was to evaluate the utility of anti-cetuximab IgE detection in order to identify patients at risk of HSR to cetuximab. METHODS: We included patients ready to receive a first cetuximab infusion in a prospective cohort carried out at 9 French centers. Pre-treatment anti-cetuximab IgE levels were measured...
September 24, 2016: British Journal of Clinical Pharmacology
Diana Braunholz, Mohammad Saki, Franziska Niehr, Merve Öztürk, Berta Borràs Puértolas, Robert Konschak, Volker Budach, Ingeborg Tinhofer
In solid tumours millions of cells are shed into the blood circulation each day. Only a subset of these circulating tumour cells (CTCs) survive, many of them presumable because of their potential to form multi-cellular clusters also named spheroids. Tumour cells within these spheroids are protected from anoikis, which allows them to metastasize to distant organs or re-seed at the primary site. We used spheroid cultures of head and neck squamous cell carcinoma (HNSCC) cell lines as a model for such CTC clusters for determining the role of the epidermal growth factor receptor (EGFR) in cluster formation ability and cell survival after detachment from the extra-cellular matrix...
2016: PloS One
Miho Ishimaru, Sachiko Ono, Sayaka Suzuki, Hiroki Matsui, Kiyohide Fushimi, Hideo Yasunaga
BACKGROUND: The purpose of this study was to compare the effect of cetuximab-based radiotherapy (RT) with cisplatin-based concomitant chemoradiotherapy (CCRT) on artificial nutrition dependence in locoregional advanced head and neck cancer. METHODS: We identified patients treated with cetuximab-based RT or CCRT between 2012 and 2014 in a Japanese national database, and used propensity score-matched analyses to evaluate artificial nutrition dependence for 30 days after starting chemotherapy and at hospital discharge...
September 16, 2016: Head & Neck
Yoann Pointreau, Nicolas Azzopardi, David Ternant, Gilles Calais, Gilles Paintaud
BACKGROUND: A retrospective study was conducted to analyze interindividual variability of cetuximab pharmacokinetics and its influence on survival (progression-free survival and overall survival [OS]) in a cohort of head and neck squamous cell carcinoma (HNSCC). METHODS: Thirty-four patients received cetuximab as an infusion loading dose of 400 mg/m followed by weekly infusions of 250 mg/m. Twenty-one patients had locally advanced HNSCC, and 13 had metastatic/recurrent HNSCC...
October 2016: Therapeutic Drug Monitoring
Chloé Rancoule, Alexis Vallard, Sophie Espenel, Jean-Baptiste Guy, Yaoxiong Xia, Anis El Meddeb Hamrouni, Claire Rodriguez-Lafrasse, Cyrus Chargari, Eric Deutsch, Nicolas Magné
Immune system deregulation and evasion play a key role in cancers' evolution and progression, including squamous cell carcinoma of the head and neck (SCCHN). Development of basic research proposed a whole new vision of cancer treatment, based on a strong biological rational, and targeting intrinsic deregulations. Immunotherapies provide an encouraging strategy for patients' improved outcomes. Immune-based therapies could act on cancer growth and/or development throughout many pathways. If cetuximab is for now the only monoclonal antibody approved for SCCHN management, other strategies, e...
September 9, 2016: Oral Oncology
M Hoffmann
The papers on human papillomavirus (HPV) infections in head and neck carcinomas presented during the ASCO Meeting in 2016 investigated factors influencing the survival of patients with known HPV status. Interestingly, women suffering from oropharyngeal carcinomas show better survival than men do. This is believed to be the consequence of differences in the immune system of male and female patients. Another interesting finding is that the HPV status in cases of locoregional recurrence of oropharyngeal carcinomas represents a positive predictive marker for patient survival...
October 2016: HNO
Doris Posch, Hannah Fuchs, Gabriela Kornek, Anja Grah, Johannes Pammer, Marie-Bernadette Aretin, Thorsten Fuereder
For patients with recurrent/metastatic (R/M) head and neck squamous cell carcinoma (SCCHN) limited therapeutic options exist. Only a subset of patients is suitable for combination chemotherapy regimens. Biweekly docetaxel plus cetuximab might be an alternative option. Thus, we performed this retrospective analysis in unselected patients in order to investigate the efficacy and safety of this regimen. Thirty-one patients receiving off protocol docetaxel (50 mg/m(2)) plus cetuximab (500 mg/m(2)) biweekly were included...
2016: Scientific Reports
Lindsay Scott Moore, Eben L Rosenthal, Thomas K Chung, Esther de Boer, Neel Patel, Andrew C Prince, Melissa L Korb, Erika M Walsh, Erik Scott Young, Todd M Stevens, Kirk P Withrow, Anthony B Morlandt, Joshua Richman, William R Carroll, Kurt R Zinn, Jason M Warram
RATIONALE: To assess the potential of US Food and Drug Administration cleared devices designed for indocyanine green-based perfusion imaging to identify cancer-specific bioconjugates with overlapping excitation and emission wavelengths. BACKGROUND: Recent clinical trials have demonstrated potential for fluorescence-guided surgery, but the time and cost of the approval process may impede clinical translation. To expedite this translation, we explored the feasibility of repurposing existing optical imaging devices for fluorescence-guided surgery...
September 1, 2016: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
Lisa Narveson, Emily Kathol, Michelle Rockey, David Henry, Dennis Grauer, Prakash Neupane
Weekly paclitaxel, carboplatin, and cetuximab (PCC) has been found to be efficacious and well-tolerated in patients with squamous cell carcinoma of the head and neck (SCCHN) with good performance status (PS) when used as induction chemotherapy. Use of PCC in incurable SCCHN in patients with poor PS or in a non-induction setting is an area which warrants further evaluation. Current recommendations for incurable disease consist of a platinum-based regimen with fluorouracil and cetuximab. Studied in patients with PS of 0 to 1, the fluorouracil-based regimens were associated with significant toxicities...
October 2016: Medical Oncology
Rachel Galot, Jean-Pascal Machiels
INTRODUCTION: The treatment of squamous cell carcinoma of the head and the neck depends on the disease's stage. In locally-advanced stage disease, multimodal treatment strategies, including surgery, radiotherapy and chemotherapy, give the best outcome in terms of overall survival. Those treatments are not without negligeable adverse events, which can lead to late debilitating toxicities. In recurrent/metastatic disease, not amenable to surgery or radiation therapy, palliative chemotherapy is the most appropriate treatment...
September 9, 2016: Expert Opinion on Drug Safety
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