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James A Bonner

James A Bonner

The University of Alabama at Birmingham
USA

Title: Anti-EGFr monoclonal antibody therapy in Head and Neck cancer

Biography

James A Bonner, MD, is the Merle M Salter Professor and Chairman, Department of Radiation Oncology, the University of Alabama at Birmingham School of Medicine (UAB), Birmingham, Alabama. Following residency and chief residency appointments in the Radiation Oncology Department at the University of Michigan, he joined the faculty at the Mayo Clinic, Rochester, Minnesota. He was a faculty member at the Mayo Clinic for 8 years prior to moving to the University of Alabama at Birmingham (UAB). While at the Mayo Clinic, the Mayo Fellows Association honored him Teacher of the Year in Radiation Oncology in 1994 and 1996, and was Co-Chair of the Lung Cancer Program of the Mayo-North Central Cancer Treatment Group (NCCTG) from 1994-1998. He is currently a Senior Advisor to the Cancer Center Director. He has had a long research interest in methods of enhancing radiosensitization such as combinations of chemotherapy or targeted therapy with radiotherapy. He has been the principal investigator of several clinical protocols and has published more than 125 manuscripts. He is a fellow of the American Society for Radiation Oncology (ASTRO). After serving in many University leadership roles, he was elected to be President of The University of Alabama Health Services Foundation (UAHSF).

Abstract

Over twenty years ago, head and neck cancers were found to have high levels of Epidermal Growth Factor Receptor (EGFr) expression. Additionally, studies emerged that showed a correlation with increased levels of EGFr and decrease locoregional control and survival for patients with head and neck cancer who were treated with radiotherapy. In-vitro and in-vivo studies of human head and neck cancers demonstrated radiosensitization with the anti-EGFr monoclonal antibody cetuximab. Th erefore, it was hypothesized that the inhibition of EGFr may lead to improved loco-regional control and survival for this group of patients. An early Phase IB/IIA trial showed that the anti-EGFr antibody cetuximab could be safely combined with radiation for the treatment of unresectable loco-regionally advanced head and neck cancer. Th is initial regimen included curative radiation with weekly cetuximab. Also, this early study showed a promising complete response rate in 13 of the 15 evaluable patients on the trial. Th erefore, a Phase III trial was performed in order to compare this regimen of radiotherapy with weekly cetuximab (8 infusions) to radiotherapy alone for patients with loco-regionally advanced head and neck cancer. Th e 3 and 5 year survival results showed 10% absolute improvements in survival (cetuximab + RT: 46% vs. RT alone: 36% at 5 years). Importantly, the addition of cetuximab to radiotherapy did not increase the incidence of grade 3/4 mucositis or dysphagia. An evaluation of the time course of mucositis and dysphagia revealed that cetuximab did not alter the time to onset or time to resolution of grade 3/4 mucositis or dysphagia. Recently, Bonner, et al. have presented the importance of HPV status for the patients in this randomized trial (ESMO: 2014) and these results will be reviewed. Based on the promising results employing cetuximab and radiotherapy, numerous investigations have been performed to evaluate new combinations of cetuximab and chemoradiotherapy for patients with loco-regionally advanced head and neck cancer. Th ese studies will be reviewed. Also, other anti-EGFr agents are being studied in various combinations with chemotherapy or radiotherapy. Finally, investigations are being performed to study combinations of targeted agents that inhibit multiple critical aspects of EGFr signaling or more than one signaling pathway.

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