Skip to main content

Treatment of neoplastic meningitis with intrathecal temozolomide.

Publication ,  Journal Article
Sampson, JH; Archer, GE; Villavicencio, AT; McLendon, RE; Friedman, AH; Bishop, WR; Bigner, DD; Friedman, HS
Published in: Clin Cancer Res
May 1999

Neoplastic meningitis (NM) results from leptomeningeal dissemination of cancers arising within the central nervous system or metastasizing to the leptomeninges from systemic neoplasms. The inability to produce therapeutic drug levels intrathecally (i.t.) with systemic administration and the minimal efficacy of chemotherapeutic agents currently available for direct i.t. use limit therapy. Temozolomide [8-carbamoyl-3-methylimidazo[5,1-d]-1,2,3,5-tetrazin-4([3H])-one] is a novel methylating agent with proven activity against intraparenchymal malignant gliomas (MGs). Insolubility of the standard formulation prevents its efficacious use as an i.t. agent, however. To overcome this obstacle, we have developed a unique microcrystalline formulation of temozolomide with greatly enhanced solubility. Treatment of athymic rats bearing subarachnoid MER- human MG xenografts with four doses of i.t. microcrystalline temozolomide over a 2-week period produced a 142% increase in median survival at individual doses of 2.2 micromol (P = 0.0073) and a >367% increase in median survival at individual doses of 6.8 micromol (P = 0.0015). At the higher dose tested, three of eight rats treated developed no neurological symptoms and had no evidence of residual tumor on histological examination after treatment. Use of this microcrystalline formulation in athymic rats bearing subarachnoid MER+ human MG xenografts increased median survival >132% (P < 0.0058) at both dose levels tested. Toxicity directly attributable to the i.t. administration of microcrystalline temozolomide was exhibited in the highest dose groups only and was limited to small patchy areas of focal demyelination involving <5% of spinal cord long tracks.

Duke Scholars

Published In

Clin Cancer Res

ISSN

1078-0432

Publication Date

May 1999

Volume

5

Issue

5

Start / End Page

1183 / 1188

Location

United States

Related Subject Headings

  • Transplantation, Heterologous
  • Temozolomide
  • Subarachnoid Space
  • Solubility
  • Rats, Nude
  • Rats
  • Oncology & Carcinogenesis
  • Neoplasm Transplantation
  • Meningeal Neoplasms
  • Humans
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Sampson, J. H., Archer, G. E., Villavicencio, A. T., McLendon, R. E., Friedman, A. H., Bishop, W. R., … Friedman, H. S. (1999). Treatment of neoplastic meningitis with intrathecal temozolomide. Clin Cancer Res, 5(5), 1183–1188.
Sampson, J. H., G. E. Archer, A. T. Villavicencio, R. E. McLendon, A. H. Friedman, W. R. Bishop, D. D. Bigner, and H. S. Friedman. “Treatment of neoplastic meningitis with intrathecal temozolomide.Clin Cancer Res 5, no. 5 (May 1999): 1183–88.
Sampson JH, Archer GE, Villavicencio AT, McLendon RE, Friedman AH, Bishop WR, et al. Treatment of neoplastic meningitis with intrathecal temozolomide. Clin Cancer Res. 1999 May;5(5):1183–8.
Sampson, J. H., et al. “Treatment of neoplastic meningitis with intrathecal temozolomide.Clin Cancer Res, vol. 5, no. 5, May 1999, pp. 1183–88.
Sampson JH, Archer GE, Villavicencio AT, McLendon RE, Friedman AH, Bishop WR, Bigner DD, Friedman HS. Treatment of neoplastic meningitis with intrathecal temozolomide. Clin Cancer Res. 1999 May;5(5):1183–1188.

Published In

Clin Cancer Res

ISSN

1078-0432

Publication Date

May 1999

Volume

5

Issue

5

Start / End Page

1183 / 1188

Location

United States

Related Subject Headings

  • Transplantation, Heterologous
  • Temozolomide
  • Subarachnoid Space
  • Solubility
  • Rats, Nude
  • Rats
  • Oncology & Carcinogenesis
  • Neoplasm Transplantation
  • Meningeal Neoplasms
  • Humans