title: Nimotuzumab with chemoradiation confers a survival advantage in treatment-naïve head and neck tumors over expressing EGFR.
abstract: Head and neck cancer associated with the chewing of betel preparations, including tobacco, is common to South East Asia. We report a Phase IIB study in which ninety-two treatment naïve patients with advanced squamous cell carcinoma received standard therapy with or without an anti-Epidermal Growth Factor Receptor (EGFR) monoclonal antibody (Nimotuzumab). In pretreatment samples, the tissue expression of ErbB family proteins and downstream molecules, including their association with clinical response and survival. Marker expression in tumor adjacent sections was evaluated by immunohistochemistry. The clinical benefit of Nimotuzumab (200 mg/dose, once a week for six weeks) in combination with radiotherapy or chemoradiation was assessed with respect to EGFR expression and intensity. Two antibodies, which recognized independent epitopes, were used to assess EGFR expression levels by immunohistochemistry. EGFR detection using mR3, an antibody with similar specificity to Nimotuzumab, correlated significantly with the expression of ErbB3 (p<0.05), PCNA and pMAPK (p<0.001). Although EGFR expression showed a significant relationship to patient survival in patients treated with Nimotuzumab and chemoradiation (p=0.02), pMAPK expression did not (p=0.07). Interestingly, EGFR overexpression (as defined by mR3) correlated directly with overall survival in this group (p=0.01). This data supports a model of basal activation of the EGFR signal transduction pathway in these oropharyngeal tumors. Detection of EGFR by immunohistochemistry could define a subset of treatment naïve Head and Neck cancer patients who may benefit from receiving EGFR targeted therapies in combination with chemoradiation.
authors.affiliation: Clinigene International Ltd, Bangalore, India.
authors.forename: Chetana
authors.initials: C
authors.lastname: Basavaraj
authors.forename: Patricia
authors.initials: P
authors.lastname: Sierra
authors.forename: Jatteppanavar
authors.initials: J
authors.lastname: Shivu
authors.forename: Ramakrishnan
authors.initials: R
authors.lastname: Melarkode
authors.forename: Enrique
authors.initials: E
authors.lastname: Montero
authors.forename: Pradip
authors.initials: P
authors.lastname: Nair
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000276:immunology; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068818:Cetuximab; D003131:Combined Modality Therapy; D004334:Drug Administration Schedule; D066246:ErbB Receptors / Q000276:immunology / Q000378:metabolism*; D005260:Female; D006258:Head and Neck Neoplasms / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D011878:Radiotherapy / Q000379:methods; D020893:Receptor, ErbB-3 / Q000378:metabolism; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018809:Proliferating Cell Nuclear Antigen; C501466:nimotuzumab; D066246:ErbB Receptors; D020893:Receptor, ErbB-3; D020928:Mitogen-Activated Protein Kinases; D000068818:Cetuximab