Antitumour effects of intravenous administration of BK-UM, a novel inhibitor of HB-EGF, in ovarian cancer therapy

Abstract

Background: Patients with ovarian cancer with high levels of heparin-binding epidermal growth factor-like growth factor have a poor prognosis. Here we assessed the pharmacokinetics and tumour-inhibiting effects of crossreacting material 197, produced commercially as BK-UM, and examined the efficacy and safety of its intravenous (i.v.) administration. Materials and Methods: BK-UM was administered to rats, and its serum levels were measured. Ovarian cancer cell lines were either intraperitoneally (i.p.) or subcutaneously administered into mice, to establish a mouse model of ovarian cancer. BK-UM was then administered i.p. or i.v., and its tumour-inhibiting effects were examined. Results: Higher maximum serum concentration (Cmax) values resulted from i.v. administration, whereas longer time to maximum serum (Tmax) values resulted from i.p. administration. In the peritoneal dissemination model, i.p. administration inhibited tumour growth and increased survival rate, whereas in the subcutaneous model, i.v. administration significantly inhibited tumour growth compared to i.p. administration. Conclusion: Administration of BK-UM by i.v. is both efficacious and safe.