title: Use of the humanized anti-epidermal growth factor receptor monoclonal antibody h-R3 in combination with radiotherapy in the treatment of locally advanced head and neck cancer patients.
abstract: OBJECTIVE
  To evaluate safety and preliminary efficacy of the humanized anti-epidermal growth factor receptor monoclonal antibody h-R3 in combination with radiotherapy (RT) in unresectable head and neck cancer patients. Secondary end points were the measurement of h-R3 serum levels and the assessment of the potential mechanisms of antitumor effect on patient biopsies. Anti-idiotypic response to h-R3 was assessed. To predict pharmacologic effect, a mathematical model for antibodies recognizing antigens expressed in tumors and normal tissues was built.
  
  
  METHODS
  Twenty-four patients with advanced carcinomas of the head and neck received six once-weekly infusions of h-R3 at four dose levels in combination with RT. Pretreatment tumor biopsies were obtained to evaluate epidermal growth factor receptor expression as an enrollment criterion. Second biopsies were taken to evaluate the proliferative activity and angiogenesis in comparison with the pretreatment samples. Patient serum samples were collected to measure h-R3 levels and anti-idiotypic response.
  
  
  RESULTS
  The combination of h-R3 and RT was well tolerated. Antibody-related adverse events consisted in infusion reactions. No skin or allergic toxicity appeared. Overall survival significantly increased after the use of the higher antibody doses. Immunohistochemistry studies of tumor specimens before and after treatment revealed that antitumor response correlated with antiproliferative and antiangiogenic effect. One patient developed antibodies to h-R3. The mathematical model predicted that the maximum difference between the area under the curve in tumors and normal tissues is reached when the antibody has intermediate affinity.
  
  
  CONCLUSIONS
  h-R3 is a well-tolerated drug that may enhance radiocurability of unresectable head and neck neoplasms.
authors.affiliation: Center of Molecular Immunology, Clinical Immunology Department, PO Box 16040, Havana 11600, Cuba. Taniac@ict.cim.sld.cu
authors.forename: Tania
authors.initials: T
authors.lastname: Crombet
authors.forename: Marta
authors.initials: M
authors.lastname: Osorio
authors.forename: Teresa
authors.initials: T
authors.lastname: Cruz
authors.forename: Carlos
authors.initials: C
authors.lastname: Roca
authors.forename: Ramón
authors.initials: R
authors.lastname: del Castillo
authors.forename: Rosa
authors.initials: R
authors.lastname: Mon
authors.forename: Normando
authors.initials: N
authors.lastname: Iznaga-Escobar
authors.forename: René
authors.initials: R
authors.lastname: Figueredo
authors.forename: James
authors.initials: J
authors.lastname: Koropatnick
authors.forename: Enrique
authors.initials: E
authors.lastname: Renginfo
authors.forename: Eduardo
authors.initials: E
authors.lastname: Fernández
authors.forename: Daniel
authors.initials: D
authors.lastname: Alvárez
authors.forename: Olga
authors.initials: O
authors.lastname: Torres
authors.forename: Mayra
authors.initials: M
authors.lastname: Ramos
authors.forename: Idrissa
authors.initials: I
authors.lastname: Leonard
authors.forename: Rolando
authors.initials: R
authors.lastname: Pérez
authors.forename: Agustín
authors.initials: A
authors.lastname: Lage
mesh_terms: D000368:Aged; D000911:Antibodies, Monoclonal / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000912:Antibodies, Neoplasm / Q000032:analysis / Q000276:immunology*; D001706:Biopsy; D002277:Carcinoma / Q000276:immunology* / Q000532:radiotherapy*; D003131:Combined Modality Therapy; D066246:ErbB Receptors / Q000276:immunology* / Q000627:therapeutic use*; D005260:Female; D006258:Head and Neck Neoplasms / Q000276:immunology* / Q000532:radiotherapy*; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; D066246:ErbB Receptors