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

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.
AuthorsH S Friedman, P J Houghton, S C Schold, S Keir, D D Bigner
JournalCancer chemotherapy and pharmacology (Cancer Chemother Pharmacol) Vol. 34 Issue 2 Pg. 171-4 ( 1994) ISSN: 0344-5704 [Print] Germany
PMID8194169 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Antineoplastic Agents
  • Topotecan
  • Camptothecin
Topics
  • Adult
  • Animals
  • Antineoplastic Agents (therapeutic use, toxicity)
  • Camptothecin (analogs & derivatives, therapeutic use, toxicity)
  • Central Nervous System Neoplasms (drug therapy, mortality)
  • Child
  • Drug Screening Assays, Antitumor
  • Female
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Neoplasm Transplantation
  • Random Allocation
  • Time Factors
  • Topotecan
  • Transplantation, Heterologous

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