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Intrathecal busulfan treatment of human neoplastic meningitis in athymic nude rats.

Publication ,  Journal Article
Archer, GE; Sampson, JH; McLendon, RE; Friedman, AH; Colvin, OM; Rose, M; Sands, H; McCullough, W; Fuchs, HE; Bigner, DD; Friedman, HS
Published in: J Neurooncol
1999

The current study was designed to evaluate the toxicity and activity of Spartaject Busulfan, a microcrystalline preparation of busulfan, following its intrathecal administration into a nude rat model of human neoplastic meningitis. Animals were treated through permanent indwelling subarachnoid catheters. Human glioma D-456 MG growing in the subarachnoid space was treated with 8.1 micromol of intrathecal Spartaject Busulfan. Single-dose therapy was also subsequently compared with 4 doses of 8.1 and 2.0 micromol busulfan, respectively, against D-456 MG neoplastic meningitis. Additional experiments evaluated a saline control versus 8.1 micromol x 1, 6.2 micromol x 4 and 4.1 micromol x 4, respectively, against D-456 MG. A single dose of 8.1 micromol of intrathecal Spartaject Busulfan resulted in an increase in median survival of 61.7% compared with the saline control. In experiment 2, all busulfan treatments showed increases in median survival of 142.8% (8.1 micromol x 1), 52.3% (2.0 micromol x 4), and 23% (8.1 micromol x 4) (p < 0.001 for all groups) compared with the saline control. These results suggest that a narrow therapeutic dose range for both toxicity and activity has been defined for intrathecal busulfan in the treatment of human neoplastic meningitis in athymic nude rats. Although busulfan has only limited activity against solid tumors, the high doses achievable in the CSF following intrathecal administration coupled with the steep dose-response relationships of alkylating agents, provide rationale for further evaluation of this agent.

Duke Scholars

Published In

J Neurooncol

DOI

ISSN

0167-594X

Publication Date

1999

Volume

44

Issue

3

Start / End Page

233 / 241

Location

United States

Related Subject Headings

  • Survival Analysis
  • Subarachnoid Space
  • Rats, Nude
  • Rats
  • Oncology & Carcinogenesis
  • Meningitis
  • Meningeal Neoplasms
  • Injections, Spinal
  • Glioblastoma
  • Female
 

Citation

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Archer, G. E., Sampson, J. H., McLendon, R. E., Friedman, A. H., Colvin, O. M., Rose, M., … Friedman, H. S. (1999). Intrathecal busulfan treatment of human neoplastic meningitis in athymic nude rats. J Neurooncol, 44(3), 233–241. https://doi.org/10.1023/a:1006304424346
Archer, G. E., J. H. Sampson, R. E. McLendon, A. H. Friedman, O. M. Colvin, M. Rose, H. Sands, et al. “Intrathecal busulfan treatment of human neoplastic meningitis in athymic nude rats.J Neurooncol 44, no. 3 (1999): 233–41. https://doi.org/10.1023/a:1006304424346.
Archer GE, Sampson JH, McLendon RE, Friedman AH, Colvin OM, Rose M, et al. Intrathecal busulfan treatment of human neoplastic meningitis in athymic nude rats. J Neurooncol. 1999;44(3):233–41.
Archer, G. E., et al. “Intrathecal busulfan treatment of human neoplastic meningitis in athymic nude rats.J Neurooncol, vol. 44, no. 3, 1999, pp. 233–41. Pubmed, doi:10.1023/a:1006304424346.
Archer GE, Sampson JH, McLendon RE, Friedman AH, Colvin OM, Rose M, Sands H, McCullough W, Fuchs HE, Bigner DD, Friedman HS. Intrathecal busulfan treatment of human neoplastic meningitis in athymic nude rats. J Neurooncol. 1999;44(3):233–241.
Journal cover image

Published In

J Neurooncol

DOI

ISSN

0167-594X

Publication Date

1999

Volume

44

Issue

3

Start / End Page

233 / 241

Location

United States

Related Subject Headings

  • Survival Analysis
  • Subarachnoid Space
  • Rats, Nude
  • Rats
  • Oncology & Carcinogenesis
  • Meningitis
  • Meningeal Neoplasms
  • Injections, Spinal
  • Glioblastoma
  • Female