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

Abstract

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.