DOSE-DEPENDENT ACCESS OF MURINE ANTIEPIDERMAL GROWTH-FACTOR RECEPTOR MONOCLONAL-ANTIBODY TO TUMOR-CELLS IN PATIENTS WITH ADVANCED LARYNGEALAND HYPOPHARYNGEAL CARCINOMA

The murine IgG2a monoclonal antibody (mAb) EMD 55900 was produced agai nst the human epidermoid carcinoma cell line A431, with binding occurr ing to the polypeptide chain of the external domain of human epidermal growth factor receptor (EGF-R). In the present clinical study, 12 pat ients with advanced squamous cell carcinoma of the larynx or hypophary nx received a single dose of either 20, 100 or 400 mg EMD 55900 3 days prior to laryngectomy and neck dissection. Clinical signs and laborat ory parameters of toxicity, development of human anti-mouse antibodies , and mAb plasma concentrations were monitored. In tumor specimens stu died from primary tumors and lymph node metastases, expression of EGF- R, distribution of EMD 55900, and occupation of EGF-R by EMD 55900 (do uble staining) were determined by immunohistochemistry. Single-dose ad ministration 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 carcinoma s studied.