title: Phase I clinical evaluation of a neutralizing monoclonal antibody against epidermal growth factor receptor in advanced brain tumor patients: preliminary study.
abstract: High levels of growth factors and their receptors have been demonstrated in human tumors. Gliomas and meningiomas are characterized by overexpression of epidermal growth factor receptor (EGF-R). Ior egf/r3, is a neutralizing murine monoclonal antibody (MAb) against EGF-R, and was generated at the Cuban Institute of Oncology. The antibody recognizes EGF-R with high affinity, inhibiting tyrosine kinase activation. A clinical trial was conducted in brain tumor patients to evaluate toxicity, immunogenicity, and clinical benefit of escalating doses of the antibody. Nine patients with histologically confirmed gliomas or meningiomas, who had active or recurrent disease after receiving conventional treatment, received four intravenous doses of ior egf/r3. Total dosages ranged from 160 to 480 mg. As inclusion criteria, radioimmunoscintigraphy with the same MAb labeled with 99mTechnetium (99mTc) was performed. Immune response against the murine antibody was also evaluated. After four doses of ior egf/r3 MAb, no significant toxicity was found, except in one patient who developed a grade 4 allergic adverse event. This reaction was probably related with previous sensitization to the same MAb and the development of human anti-mouse antibodies (HAMA) response. Despite no major objective antitumor responses, eight patients had stable disease on the 6-month evaluation, and two patients remain alive after four years of MAb therapy.
authors.affiliation: Center of Molecular Immunology, Havana, Cuba. Taniac@ict.cim.sld.cu
authors.forename: T
authors.initials: T
authors.lastname: Crombet
authors.forename: O
authors.initials: O
authors.lastname: Torres
authors.forename: V
authors.initials: V
authors.lastname: Rodríguez
authors.forename: A
authors.initials: A
authors.lastname: Menéndez
authors.forename: A
authors.initials: A
authors.lastname: Stevenson
authors.forename: M
authors.initials: M
authors.lastname: Ramos
authors.forename: F
authors.initials: F
authors.lastname: Torres
authors.forename: R
authors.initials: R
authors.lastname: Figueredo
authors.forename: I
authors.initials: I
authors.lastname: Veitía
authors.forename: N
authors.initials: N
authors.lastname: Iznaga
authors.forename: R
authors.initials: R
authors.lastname: Pérez
authors.forename: A
authors.initials: A
authors.lastname: Lage
mesh_terms: D000328:Adult; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000627:therapeutic use / Q000633:toxicity; D001254:Astrocytoma / Q000150:complications / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000378:metabolism; D001932:Brain Neoplasms / Q000150:complications / Q000000981:diagnostic imaging* / Q000188:drug therapy* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D066246:ErbB Receptors / Q000276:immunology* / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008579:Meningioma / Q000150:complications / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000378:metabolism; D051379:Mice; D008875:Middle Aged; D016719:Radioimmunodetection; D013667:Technetium; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D013667:Technetium; D066246:ErbB Receptors