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Intrathecal melphalan therapy of human neoplastic meningitis in athymic nude rats.

Publication ,  Journal Article
Friedman, HS; Archer, GE; McLendon, RE; Schuster, JM; Colvin, OM; Guaspari, A; Blum, R; Savina, PA; Fuchs, HE; Bigner, DD
Published in: Cancer Res
September 1, 1994

We report the activity and toxicity of intrathecal melphalan in the treatment of human neoplastic meningitis in the subarachnoid space of athymic nude rats. Animals received injections via chronic indwelling subarachnoid catheters with 5 x 10(5) or 5 x 10(6) TE-671 human rhabdomyosarcoma cells or 5 x 10(6) D-54 MG human glioma cells and were treated with melphalan on days 8, 5, or 5, respectively. Melphalan toxicity in nontumor-bearing rats was assessed at single doses of a 2.0, 3.0, 4.0, or 5.0 mM solution, with clinical and histological evidence of neurotoxicity observed at the 4.0 and 5.0 mM levels. Multiple-dose toxicity studies using a dosing schedule of twice a week for two weeks with a 0.25, 0.5, 0.75, 1.0, 1.5, or 2 mM solution revealed dose-dependent clinical and histological evidence for toxicity at all dosages. Treatment of TE-671 with a single dose of 2.0 mM intrathecal melphalan produced an increase in median survival of 442% compared with saline controls (P < 0.003). Comparison of a single dose of 1.0 or 2.0 mM melphalan with a multiple dose regimen at 0.25 or 0.5 mM melphalan in the treatment of TE-671 revealed increases in median survival of 50% for 1.0 mM, 57% for 2.0 mM, 79% for 0.5 mM, and 111% for 0.25 mM concentrations. Comparison of a single dose of 1 mM melphalan with multiple doses of 0.25 mM melphalan in the treatment of D-54 MG revealed an increase in median survival of 475+% for each of the regimens. Intrathecal melphalan may be an important new addition in the treatment of neoplastic meningitis and is currently being evaluated clinically in a Phase 1 trial.

Duke Scholars

Published In

Cancer Res

ISSN

0008-5472

Publication Date

September 1, 1994

Volume

54

Issue

17

Start / End Page

4710 / 4714

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Transplantation, Heterologous
  • Subarachnoid Space
  • Rhabdomyosarcoma
  • Rats, Nude
  • Rats
  • Oncology & Carcinogenesis
  • Meningitis
  • Melphalan
  • Injections, Spinal
 

Citation

APA
Chicago
ICMJE
MLA
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Friedman, H. S., Archer, G. E., McLendon, R. E., Schuster, J. M., Colvin, O. M., Guaspari, A., … Bigner, D. D. (1994). Intrathecal melphalan therapy of human neoplastic meningitis in athymic nude rats. Cancer Res, 54(17), 4710–4714.
Friedman, H. S., G. E. Archer, R. E. McLendon, J. M. Schuster, O. M. Colvin, A. Guaspari, R. Blum, P. A. Savina, H. E. Fuchs, and D. D. Bigner. “Intrathecal melphalan therapy of human neoplastic meningitis in athymic nude rats.Cancer Res 54, no. 17 (September 1, 1994): 4710–14.
Friedman HS, Archer GE, McLendon RE, Schuster JM, Colvin OM, Guaspari A, et al. Intrathecal melphalan therapy of human neoplastic meningitis in athymic nude rats. Cancer Res. 1994 Sep 1;54(17):4710–4.
Friedman, H. S., et al. “Intrathecal melphalan therapy of human neoplastic meningitis in athymic nude rats.Cancer Res, vol. 54, no. 17, Sept. 1994, pp. 4710–14.
Friedman HS, Archer GE, McLendon RE, Schuster JM, Colvin OM, Guaspari A, Blum R, Savina PA, Fuchs HE, Bigner DD. Intrathecal melphalan therapy of human neoplastic meningitis in athymic nude rats. Cancer Res. 1994 Sep 1;54(17):4710–4714.

Published In

Cancer Res

ISSN

0008-5472

Publication Date

September 1, 1994

Volume

54

Issue

17

Start / End Page

4710 / 4714

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Transplantation, Heterologous
  • Subarachnoid Space
  • Rhabdomyosarcoma
  • Rats, Nude
  • Rats
  • Oncology & Carcinogenesis
  • Meningitis
  • Melphalan
  • Injections, Spinal