Dose-dependent access of murine anti-epidermal growth factor receptor monoclonal antibody to tumor cells in patients with advanced laryngeal and hypopharyngeal carcinoma.
The murine IgG2a monoclonal antibody (mAb) EMD 55900 was produced against the human epidermoid carcinoma cell line A431, with binding occurring to the polypeptide chain of the external domain of human epidermal growth factor receptor (EGF-R). In the present clinical study, 12 patients with advanced squamous cell carcinoma of the larynx or hypopharynx received a single dose of either 20, 100 or 400 mg EMD 55900 3 days prior to laryngectomy and neck dissection. Clinical signs and laboratory parameters of toxicity, development of human anti-mouse antibodies, and mAb plasma concentrations were monitored. In tumor specimens studied from primary tumors and lymph node metastases, expression of EGF-R, distribution of EMD 55900, and occupation of EGF-R by EMD 55900 (double staining) were determined by immunohistochemistry. Single-dose administration of EMD 55900 was very well tolerated in all patients, and good (100 mg) to excellent (400 mg) homogeneous binding of mAb to EGF-R was obtained in the advanced laryngeal and hypopharyngeal carcinomas studied.
Bier
H
H
Department of Otolaryngology/Head and Neck Surgery, Heinrich Heine University Hospital, Düsseldorf, Germany.
Reiffen
K A
KA
Haas
I
I
Stasiecki
P
P
D000328:Adult; D000818:Animals; D000911:Antibodies, Monoclonal / Q000032:analysis / Q000097:blood / Q000276:immunology / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000473:pathology / Q000556:secondary / Q000601:surgery / Q000628:therapy*; D003131:Combined Modality Therapy; D004306:Dose-Response Relationship, Immunologic; D004361:Drug Tolerance; D066246:ErbB Receptors / Q000032:analysis / Q000235:genetics / Q000276:immunology*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007012:Hypopharyngeal Neoplasms / Q000473:pathology / Q000601:surgery / Q000628:therapy*; D007074:Immunoglobulin G / Q000032:analysis / Q000097:blood / Q000276:immunology / Q000627:therapeutic use*; D007150:Immunohistochemistry; D007822:Laryngeal Neoplasms / Q000473:pathology / Q000601:surgery / Q000628:therapy*; D007825:Laryngectomy; D008197:Lymph Node Excision; D008207:Lymphatic Metastasis / Q000473:pathology; D051379:Mice; D008875:Middle Aged
D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D066246:ErbB Receptors