Abstract 1557: Corticorelin acetate exhibits preclinical antitumor activity, alone and with bevacizumab, against human brain tumor models

Corticorelin acetate is a synthetic form of corticotropin-releasing factor undergoing clinical trials in the treatment of peritumoral brain edema. We investigated preclinically its potential as an antitumor agent against orthotopically implanted human brain tumors, and its ability to enhance the therapeutic activity of bevacizumab in one of these models. Intracranial (ic) tumor transplantation into the right cerebrum was performed using two patient-derived human tumor xenografts: D-341MED pediatric medulloblastoma and D-456MG pediatric multiforme glioblastoma. Mice were randomized 3 days after ic tumor implantation at which time all treatments were begun. Corticorelin acetate was administered at 0.1 and/or 0.2 mg mg/kg/dose, sc, twice daily (bid) depending upon the experiment. Bevacizumab was administered at a dose of 5 mg/kg/day, intraperitoneally (ip), twice weekly. Treatments were continued until a median day of death was reached for each group. In both studies antitumor effects were evaluated based on a survival analysis (Kaplan-Meier). In the D-341MED, comparing treatments vs control, the low dose corticorelin acetate produced a 56% increase in life span (ILS) (p Conclusion: Corticorelin acetate significantly increased the lifespan of mice implanted orthotopically with two different pediatric brain tumor models. In the D-456MG model, in which corticorelin acetate and bevacizumab were evaluated, the combination produced a therapeutic outcome superior to that found using either of the two agents alone. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1557.