Skip to main content

Activity of intrathecal 4-hydroperoxycyclophosphamide in a nude rat model of human neoplastic meningitis.

Publication ,  Journal Article
Fuchs, HE; Archer, GE; Colvin, OM; Bigner, SH; Schuster, JM; Fuller, GN; Muhlbaier, LH; Schold, SC; Friedman, HS; Bigner, DD
Published in: Cancer Res
March 15, 1990

Neoplastic meningitis can result from leptomeningeal dissemination of a variety of cancers. We now report the development of animal models of human neoplastic meningitis and activity of intrathecal 4-hydroperoxycyclophosphamide (4-HC) against the human rhabdomyosarcoma cell line TE-671 and the human glioma cell line D-54 MG grown in the subarachnoid space of athymic rats. The injection of 5 x 10(5) TE-671 or D-54 MG cells resulted in leptomeningeal tumor growth from the base of the brain to the cauda equina. Daily weights and neurological examinations revealed progressive neurological deficits and weight loss, with death occurring between Days 21 and 27 for TE-671 and Days 14 and 26 for D-54 MG. 4-HC toxicity in non-tumor-bearing rats was assessed at dose levels of 2.0, 10.0, 15.0, and 20.0 mM, with clinical and histological evidence of neurotoxicity observed at the 2 highest dose levels. Intrathecal treatment with 4-HC on Day 8 following injection of TE-671 resulted in an increase in median survival of 20% (P = 0.04) at 1.0 mM 4-HC and 41% (P less than 0.001) at 2.5 mM 4-HC. Intrathecal treatment with 4-HC (2.5 mM) on Day 5 following injection of D-54 MG resulted in an increase in median survival of 23% (P = 0.009). These studies show the usefulness of the athymic rat model of human neoplastic meningitis and demonstrate the efficacy in vivo of intrathecally administered 4-HC against a human glioma and a human rhabdomyosarcoma cell line and the lack of toxicity at therapeutic levels of 4-HC in normal athymic rats.

Duke Scholars

Published In

Cancer Res

ISSN

0008-5472

Publication Date

March 15, 1990

Volume

50

Issue

6

Start / End Page

1954 / 1959

Location

United States

Related Subject Headings

  • Transplantation, Heterologous
  • Spinal Cord Neoplasms
  • Rhabdomyosarcoma
  • Rats, Nude
  • Rats
  • Oncology & Carcinogenesis
  • Neoplasm Transplantation
  • Meningitis
  • Meningeal Neoplasms
  • Injections, Spinal
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Fuchs, H. E., Archer, G. E., Colvin, O. M., Bigner, S. H., Schuster, J. M., Fuller, G. N., … Bigner, D. D. (1990). Activity of intrathecal 4-hydroperoxycyclophosphamide in a nude rat model of human neoplastic meningitis. Cancer Res, 50(6), 1954–1959.
Fuchs, H. E., G. E. Archer, O. M. Colvin, S. H. Bigner, J. M. Schuster, G. N. Fuller, L. H. Muhlbaier, S. C. Schold, H. S. Friedman, and D. D. Bigner. “Activity of intrathecal 4-hydroperoxycyclophosphamide in a nude rat model of human neoplastic meningitis.Cancer Res 50, no. 6 (March 15, 1990): 1954–59.
Fuchs HE, Archer GE, Colvin OM, Bigner SH, Schuster JM, Fuller GN, et al. Activity of intrathecal 4-hydroperoxycyclophosphamide in a nude rat model of human neoplastic meningitis. Cancer Res. 1990 Mar 15;50(6):1954–9.
Fuchs, H. E., et al. “Activity of intrathecal 4-hydroperoxycyclophosphamide in a nude rat model of human neoplastic meningitis.Cancer Res, vol. 50, no. 6, Mar. 1990, pp. 1954–59.
Fuchs HE, Archer GE, Colvin OM, Bigner SH, Schuster JM, Fuller GN, Muhlbaier LH, Schold SC, Friedman HS, Bigner DD. Activity of intrathecal 4-hydroperoxycyclophosphamide in a nude rat model of human neoplastic meningitis. Cancer Res. 1990 Mar 15;50(6):1954–1959.

Published In

Cancer Res

ISSN

0008-5472

Publication Date

March 15, 1990

Volume

50

Issue

6

Start / End Page

1954 / 1959

Location

United States

Related Subject Headings

  • Transplantation, Heterologous
  • Spinal Cord Neoplasms
  • Rhabdomyosarcoma
  • Rats, Nude
  • Rats
  • Oncology & Carcinogenesis
  • Neoplasm Transplantation
  • Meningitis
  • Meningeal Neoplasms
  • Injections, Spinal