Anti-EGFr Monoclonal Antibody Therapy In Head And Neck Cancer | 25722
Otolaryngology: Open Access
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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.
Therefore, 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. This 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. Therefore, 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. The 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. These 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.
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).
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