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.
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.
Authors: Matthew Gallitto; Stanislav Lazarev; Isaac Wasserman; James M Stafford; Suzanne L Wolden; Stephanie A Terezakis; Ranjit S Bindra; Richard L Bakst Journal: Adv Radiat Oncol Date: 2019-03-30
Authors: Jack M Su; Lindsay B Kilburn; David B Mansur; Mark Krailo; Allen Buxton; Adesina Adekunle; Amar Gajjar; Peter C Adamson; Brenda Weigel; Elizabeth Fox; Susan M Blaney; Maryam Fouladi Journal: Neuro Oncol Date: 2022-04-01 Impact factor: 13.029