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Etoposide, vincristine, and cyclosporin a with standard-dose radiation therapy in newly diagnosed diffuse intrinsic brainstem gliomas: A pediatric oncology group Phase I study
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Etoposide, vincristine, and cyclosporin a with standard-dose radiation therapy in newly diagnosed diffuse intrinsic brainstem gliomas: A pediatric oncology group Phase I study PEDIATRIC BLOOD & CANCER Greenberg, M. L., Fisher, P. G., Freeman, C., Korones, D. N., Bernstein, M., Friedman, H., Blaney, S., Hershon, L., Zhou, T. N., Chen, Z. J., Kretschmar, C. 2005; 45 (5): 644-648Abstract
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.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.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.This regimen proved excessively toxic.
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