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Activity of temozolomide in the treatment of central nervous system tumor xenografts.

Publication ,  Journal Article
Friedman, HS; Dolan, ME; Pegg, AE; Marcelli, S; Keir, S; Catino, JJ; Bigner, DD; Schold, SC
Published in: Cancer Res
July 1, 1995

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.

Duke Scholars

Published In

Cancer Res

ISSN

0008-5472

Publication Date

July 1, 1995

Volume

55

Issue

13

Start / End Page

2853 / 2857

Location

United States

Related Subject Headings

  • Transplantation, Heterologous
  • Temozolomide
  • Procarbazine
  • Oncology & Carcinogenesis
  • O(6)-Methylguanine-DNA Methyltransferase
  • Neoplasm Transplantation
  • Mice, Nude
  • Mice, Inbred BALB C
  • Mice
  • Methyltransferases
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Friedman, H. S., Dolan, M. E., Pegg, A. E., Marcelli, S., Keir, S., Catino, J. J., … Schold, S. C. (1995). Activity of temozolomide in the treatment of central nervous system tumor xenografts. Cancer Res, 55(13), 2853–2857.
Friedman, H. S., M. E. Dolan, A. E. Pegg, S. Marcelli, S. Keir, J. J. Catino, D. D. Bigner, and S. C. Schold. “Activity of temozolomide in the treatment of central nervous system tumor xenografts.Cancer Res 55, no. 13 (July 1, 1995): 2853–57.
Friedman HS, Dolan ME, Pegg AE, Marcelli S, Keir S, Catino JJ, et al. Activity of temozolomide in the treatment of central nervous system tumor xenografts. Cancer Res. 1995 Jul 1;55(13):2853–7.
Friedman, H. S., et al. “Activity of temozolomide in the treatment of central nervous system tumor xenografts.Cancer Res, vol. 55, no. 13, July 1995, pp. 2853–57.
Friedman HS, Dolan ME, Pegg AE, Marcelli S, Keir S, Catino JJ, Bigner DD, Schold SC. Activity of temozolomide in the treatment of central nervous system tumor xenografts. Cancer Res. 1995 Jul 1;55(13):2853–2857.

Published In

Cancer Res

ISSN

0008-5472

Publication Date

July 1, 1995

Volume

55

Issue

13

Start / End Page

2853 / 2857

Location

United States

Related Subject Headings

  • Transplantation, Heterologous
  • Temozolomide
  • Procarbazine
  • Oncology & Carcinogenesis
  • O(6)-Methylguanine-DNA Methyltransferase
  • Neoplasm Transplantation
  • Mice, Nude
  • Mice, Inbred BALB C
  • Mice
  • Methyltransferases