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.


METHODS
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.


CONCLUSIONS
This regimen proved excessively toxic.
Greenberg
Mark L
ML
Hospital for Sick Children, Toronto, Ontario, Canada. mark.greenberg@sickkids.ca
Fisher
Paul G
PG
Freeman
Carolyn
C
Korones
David N
DN
Bernstein
Mark
M
Friedman
Henry
H
Blaney
Susan
S
Hershon
Linda
L
Zhou
Tianni
T
Chen
Zhengjia
Z
Kretschmar
Cynthia
C
D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D020295:Brain Stem Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D016572:Cyclosporine / Q000008:administration & dosage / Q000009:adverse effects; D018450:Disease Progression; D019583:Dose Fractionation, Radiation; D005047:Etoposide / Q000008:administration & dosage / Q000009:adverse effects; D005910:Glioma / Q000188:drug therapy* / Q000532:radiotherapy; D006801:Humans; D011879:Radiotherapy Dosage; D014750:Vincristine / Q000008:administration & dosage / Q000009:adverse effects
D014750:Vincristine; D005047:Etoposide; D016572:Cyclosporine