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Paulina J Paszkiewicz, Simon P Fräßle, Shivani Srivastava, Daniel Sommermeyer, Michael Hudecek, Ingo Drexler, Michel Sadelain, Lingfeng Liu, Michael C Jensen, Stanley R Riddell, Dirk H Busch
The adoptive transfer of T cells that have been genetically modified to express a CD19-specific chimeric antigen receptor (CAR) is effective for treating human B cell malignancies. However, the persistence of functional CD19 CAR T cells causes sustained depletion of endogenous CD19+ B cells and hypogammaglobulinemia. Thus, there is a need for a mechanism to ablate transferred T cells after tumor eradication is complete to allow recovery of normal B cells. Previously, we developed a truncated version of the epidermal growth factor receptor (EGFRt) that is coexpressed with the CAR on the T cell surface...
October 17, 2016: Journal of Clinical Investigation
Carsten Nieder
No abstract text is available yet for this article.
October 18, 2016: Strahlentherapie und Onkologie: Organ der Deutschen Röntgengesellschaft ... [et Al]
Cecilia Ferreira da Silva, Miriam Ventura da Silva, Claudia Garcia Serpa Osorio-de-Castro
Objective To analyze the pathway of clinical trials of monoclonal antibodies and biological medicines for cancer treatment involving Brazilian institutions from 2003 to 2012. Method This retrospective, descriptive study was based on review of two clinical trial registries, and the Brazilian registry ReBEC. Phase II or III studies with participation from Brazilian institutions listed in at least one of the registries were included. Following selection of the trials, the pathway of monoclonal antibodies and biological medicines was investigated from the research stage until licensing by the Brazilian Agency for Sanitary Surveillance (Anvisa), Food and Drug Administration (FDA), and European Medicines Agency (EMA)...
March 2016: Revista Panamericana de Salud Pública, Pan American Journal of Public Health
Taehwan Park, Chang-Ju Choi, Yeera Choi, Dong-Churl Suh
Cetuximab is a novel biological agent with superior therapeutic efficacy for colorectal cancer treatment. This study aimed to systematically review the existing evidence related to the cost-effectiveness of cetuximab. Areas covered: Using Medline and Cochrane Database of Systematic Reviews, a total of 12 articles were identified. Previous studies have shown mixed results on the cost-effectiveness of first-line cetuximab combined with FOLFIRI (5-Fluorouracil, leucovorin, irinotecan). However, cetuximab-irinotecan therapy as third-line treatment has consistently been found to be cost-ineffective compared to best supportive care or no third-line therapy...
October 18, 2016: Expert Review of Pharmacoeconomics & Outcomes Research
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
Carmine Pinto, Francesca Di Fabio, Gerardo Rosati, Ivan R Lolli, Enzo M Ruggeri, Libero Ciuffreda, Daris Ferrari, Giovanni Lo Re, Giovanni Rosti, Paolo Tralongo, Raimondo Ferrara, Oscar Alabiso, Silvana Chiara, Giovanni P Ianniello, Antonio Frassoldati, Domenico Bilancia, Giovanna A Campanella, Carlo Signorelli, Patrizia Racca, Elena Benincasa, Maria Elena Stroppolo, Francesco Di Costanzo
Cetuximab improves efficacy when added to chemotherapy for metastatic colorectal cancer (mCRC). Effective management of skin reactions from cetuximab improves quality of life (QoL), and treatment compliance in clinical trials. No data are available from real-world settings. The ObservEr observational, multicenter, prospective study evaluated QoL, the incidence of skin reactions, and management of chemotherapy plus cetuximab in first-line for mCRC. The primary endpoint was QoL measured with the Dermatology Life Quality Index (DLQI) and EORTC QLQ-C30...
October 17, 2016: Cancer Medicine
Jun Gong, May Cho, Marwan Fakih
The treatment of metastatic colorectal cancer (mCRC) has been further refined with the development of monoclonal antibodies, cetuximab and panitumumab, towards the epidermal growth factor receptor (EGFR). Anti-EGFR therapy has afforded improved survival in those with wild-type RAS mCRC but provides no benefit and even harm in those with RAS-mutant tumors. BRAF mutations have also been shown to predict lack of clinically meaningful benefit to anti-EGFR therapy in mCRC. Mechanisms of resistance to EGFR blockade in wild-type RAS or BRAF metastatic colorectal tumors appear to converge on the mitogen-activated protein kinase (MAPK) signaling pathway...
October 2016: Journal of Gastrointestinal Oncology
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
Junxiong Wang, Shuo Yang, Xiqiang Cai, Jiaqiang Dong, Zhangqian Chen, Rui Wang, Song Zhang, Haichao Cao, Di Lu, Tong Jin, Yongzhan Nie, Jianyu Hao, Daiming Fan
Cetuximab plus chemotherapy for advanced gastric cancer (GC) shows an active result in phase 2 trials. Unfortunately, Combination of cetuximab does not provide enough benefit to chemotherapy alone in phase 3 trials. Studies have demonstrated that berberine can suppress the activation of EGFR in tumors. In this study, we evaluated whether berberine could enhance the effects of EGFR-TKIs in GC cell lines and xenograft models. Our data suggest that berberine could effectively enhance the activity of erlotinib and cetuximab in vitro and in vivo...
October 12, 2016: Oncotarget
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
David S Hong, Van K Morris, Badi El Osta, Alexey V Sorokin, Filip Janku, Siqing Fu, Michael J Overman, Sarina Piha-Paul, Vivek Subbiah, Bryan Kee, Apostolia Tsimberidou, David Fogelman, Jorge Bellido, Imad Shureiqi, Helen Huang, Johnique Atkins, Gabi Tarcic, Nicolas Sommer, Richard Lanman, Funda Meric-Bernstam, Scott Kopetz
In vitro, EGFR inhibition, combined with the BRAF inhibitor vemurafenib, causes synergistic cytotoxicity for BRAFV600E metastatic colorectal cancer (mCRC), further augmented by irinotecan. The safety and efficacy of vemurafenib, irinotecan, and cetuximab in BRAF-mutated malignancies are not defined. In this 3+3 phase I study, patients with BRAFV600E advanced solid cancers received cetuximab and irinotecan with escalating doses of vemurafenib. Nineteen patients (18 with mCRC, 1 with appendiceal cancer) were enrolled...
October 11, 2016: Cancer Discovery
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
Sabine Tejpar, Sebastian Stintzing, Fortunato Ciardiello, Josep Tabernero, Eric Van Cutsem, Frank Beier, Regina Esser, Heinz-Josef Lenz, Volker Heinemann
Importance: Metastatic colorectal cancer (mCRC) is heterogeneous, and primary tumors arising from different regions of the colon are clinically and molecularly distinct. Objective: To examine the prognostic and predictive value of primary tumor location in patients with RAS wild-type (wt) mCRC treated with first-line fluorouracil, leucovorin, and irinotecan (FOLFIRI) plus cetuximab in the Cetuximab Combined With Irinotecan in First-line Therapy for Metastatic Colorectal Cancer (CRYSTAL) trial and FOLFIRI Plus Cetuximab Versus FOLFIRI Plus Bevacizumab as First-Line Treatment For Patients With Metastatic Colorectal Cancer (FIRE-3) trial...
October 10, 2016: JAMA Oncology
Robert L Ferris, George Blumenschein, Jerome Fayette, Joel Guigay, A Dimitrios Colevas, Lisa Licitra, Kevin Harrington, Stefan Kasper, Everett E Vokes, Caroline Even, Francis Worden, Nabil F Saba, Lara C Iglesias Docampo, Robert Haddad, Tamara Rordorf, Naomi Kiyota, Makoto Tahara, Manish Monga, Mark Lynch, William J Geese, Justin Kopit, James W Shaw, Maura L Gillison
Background Patients with recurrent or metastatic squamous-cell carcinoma of the head and neck after platinum chemotherapy have a very poor prognosis and limited therapeutic options. Nivolumab, an anti-programmed death 1 (PD-1) monoclonal antibody, was assessed as treatment for this condition. Methods In this randomized, open-label, phase 3 trial, we assigned, in a 2:1 ratio, 361 patients with recurrent squamous-cell carcinoma of the head and neck whose disease had progressed within 6 months after platinum-based chemotherapy to receive nivolumab (at a dose of 3 mg per kilogram of body weight) every 2 weeks or standard, single-agent systemic therapy (methotrexate, docetaxel, or cetuximab)...
October 8, 2016: New England Journal of Medicine
Timothy Price, Tae Won Kim, Jin Li, Stefano Cascinu, Paul Ruff, Attili Satya Suresh, Anne Thomas, Sergei Tjulandin, Xuesong Guan, Marc Peeters
PURPOSE: The primary analysis of the ASPECCT study demonstrated that panitumumab was non-inferior to cetuximab for overall survival (OS) in patients with chemotherapy-refractory wild-type KRAS exon 2 metastatic colorectal cancer (mCRC). Here, we report the final analysis results of ASPECCT. PATIENTS AND METHODS: Patients with wild-type KRAS exon 2 mCRC who progressed on or were intolerant to irinotecan- or oxaliplatin-based chemotherapy were randomised to receive panitumumab 6 mg/kg once every 2 weeks or cetuximab (400 mg/m(2)) followed by 250 mg/m(2) weekly...
October 4, 2016: European Journal of Cancer
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
Martin J Hicks, Maria J Chiuchiolo, Douglas Ballon, Jonathan P Dyke, Eric Aronowitz, Kosuke Funato, Viviane Tabar, David Havlicek, Fan Fan, Dolan Sondhi, Stephen M Kaminsky, Ronald G Crystal
Glioblastoma multiforme (GBM) is the most common and aggressive primary intracranial brain tumor in adults with a mean survival of 14 to 15 months. Aberrant activation of the epidermal growth factor receptor (EGFR) plays a significant role in GBM progression, with amplification or overexpression of EGFR in 60% of GBM tumors. To target EGFR expressed by GBM, we have developed a strategy to deliver the coding sequence for cetuximab, an anti-EGFR antibody, directly to the CNS using an adeno-associated virus serotype rh...
2016: PloS One
Valerio Gelfo, Maria Teresa Rodia, Michela Pucci, Massimiliano Dall'Ora, Spartaco Santi, Rossella Solmi, Lee Roth, Moshit Lindzen, Massimiliano Bonafè, Andrea Bertotti, Elisabetta Caramelli, Pier-Luigi Lollini, Livio Trusolino, Yosef Yarden, Gabriele D'Uva, Mattia Lauriola
Epidermal Growth Factor Receptor (EGFR) activates a robust signalling network to which colon cancer tumours often become addicted. Cetuximab, one of the monoclonal antibodies targeting this pathway, is employed to treat patients with colorectal cancer. However, many patients are intrinsically refractory to this treatment, and those who respond develop secondary resistance along time. Mechanisms of cancer cell resistance include either acquisition of new mutations or non genomic activation of alternative signalling routes...
September 30, 2016: Oncotarget
Johannes A Langendijk, Roel J H M Steenbakkers
Concurrent chemoradiation is considered the golden standard in the treatment of locally advanced OPC. However, given the very high survival rates in favorable HPV-positive OPC and the high rates of acute and late treatment-related side effects, de-escalation strategies have to be considered. In this chapter, the potential benefit of a number of de-escalation strategies is described, including of replacement of concurrent chemotherapy by cetuximab, radiation dose de-escalation based on response to induction chemotherapy, radiotherapy alone without systemic treatment, and limiting elective nodal target volumes for radiation...
2017: Recent Results in Cancer Research
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