Activity of 9-dimethylaminomethyl-10-hydroxycamptothecin against pediatric and adult central nervous system tumor xenografts

Henry S. Friedman, Peter J. Houghton, S. Clifford Schold, Stephen Keir, Darell D. Bigner

Research output: Contribution to journalArticlepeer-review

83 Scopus citations

Abstract

The activity of dimethylaminomethyl-10-hydroxycamptothecin (topotecan) was evaluated against a panel of xenografts derived from ependymomas (D528 EP, D612 EP), childhood high-grade gliomas (D-456 MG, D-212 MG), adult high-grade gliomas (D-245 MG, D-54 MG), and medulloblastomas (D425 Med) growing s.c. and i.c. (intracranially) in athymic nude mice. Topotecan was given at a dose of 1.9 mg/kg by i.p. injection in 0.9% saline using a volume of 90 ml/m2 on days 1-5 and 8-12, which represents the dose lethal to 10% of treated animals. Topotecan was active in the therapy of all s.c. xenografts tested, with growth delays ranging from 6.3 days in D-54 MG to 55.7 days in D528 EP. Topotecan produced statistically significant tumor regressions in D425 Med, D-456 MG, D-245 MG, D528 EP, and D612 EP. No tumor regression was seen in any control animal. Statistically significant increases in median survival were seen in the two i.c. xenografts - D-456 MG (28.6% increase) and D-54 MG (39% increase) -treated with topotecan. These studies suggest that topotecan may be an important new addition to the therapy of central nervous system tumors.

Original languageEnglish (US)
Pages (from-to)171-174
Number of pages4
JournalCancer chemotherapy and pharmacology
Volume34
Issue number2
DOIs
StatePublished - Mar 1994
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Toxicology
  • Pharmacology
  • Cancer Research
  • Pharmacology (medical)

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