Etoposide, vincristine, and cyclosporin A with standard-dose radiation therapy in newly diagnosed diffuse intrinsic brainstem gliomas: A pediatric oncology group phase I study

Background Brainstem gliomas (BSGs) are resistant to all therapy. Based on their imaging characteristics, we postulated that inhibition of P‐glycoprotein (P‐gp) associated with endothelial cells of the blood‐brain barrier might enhance penetration of xenobiotic antineoplastics. Procedure Seven patients were enrolled in a Phase I study of etoposide, continuous infusion cyclosporine A given with and escalating doses of vincristine and concomitant standard‐dose irradiation. Results Six patients were entered at the first level and one at the second. Closure of the study was mandated by dose‐limiting neurotoxicity, consisting of seizures associated with white‐matter changes, and alteration of consciousness with bulbar signs. One patient had tumor necrosis at 6 weeks, suggesting some tumor effect. Median survival for the group was 11 months, and for the patients who completed more than 1 month of therapy it was 11 months. Conclusion This regimen proved excessively toxic. © 2005 Wiley‐Liss, Inc.