RT Journal Article
SR Electronic
T1 Activity of Temozolomide in the Treatment of Central Nervous System Tumor Xenografts
JF Cancer Research
JO Cancer Res
FD American Association for Cancer Research
SP 2853
OP 2857
VO 55
IS 13
A1 Friedman, Henry S.
A1 Dolan, M. Eileen
A1 Pegg, Anthony E.
A1 Marcelli, Susan
A1 Keir, Stephen
A1 Catino, Joseph J.
A1 Bigner, Darell D.
A1 Schold, S. Clifford
YR 1995
UL http://cancerres.aacrjournals.org/content/55/13/2853.abstract
AB The activity of 8-carbamoyl-3-methylimidazo[5,1-d]-1,2,3,5-tetrazin-4(3H)-one (temozolomide) in the treatment of a panel of xenografts derived from ependymoma, medulloblastoma, and childhood and adult high-grade glioma was evaluated in athymic nude mice bearing s.c. and intracranial tumors. Temozolomide administered daily for a total of five doses demonstrated marked activity against a panel of Mer+ xenografts despite marginal to moderate activity of 1,3-bis(2-chloroethyl)-1-nitrosourea. The growth delays produced by temozolomide in these xenografts were 1.8–7.5-fold greater than those produced by procarbazine. Although temozolomide demonstrated marginal activity against the Mer+ cell line D341 Med when a 5-day schedule was used, a high-dose 1-day schedule resulted in moderate activity. Temozolomide produced increases in median survival of 1285% (adult glioma D-54 MG), 323% (childhood glioma D-456 MG), and 68% (ependymoma D612 EP). Pretreatment of mice with O6-benzylguanine increased temozolomide-induced mortality, requiring reduction of the dosage from 1200 to 750 mg/m2 on the single-day regimen. O6-Benzylguanine pretreatment of mice bearing Mer+ D341 Med increased the growth delay of temozolomide, in duplicate experiments, from -3.1 to 4.8 and 1.1 to 4.9 days. These studies suggest that temozolomide may be active in the treatment of a broad spectrum of central nervous system cancers, including Mer+ tumors resistant to 1,3-bis(2-chloroethyl)-1-nitrosourea. ©1995 American Association for Cancer Research.