Schedule-dependent activity of irinotecan plus BCNU against malignant glioma xenografts.

Journal Article

PURPOSE: To further evaluate the activity of irinotecan (CPT-11) plus 1,3-bis-(chloroethyl)-1-nitrosourea (BCNU) in the treatment of central nervous system tumor-derived xenografts in athymic nude mice. METHODS: We report studies evaluating the schedule-dependence of this regimen in the treatment of the malignant glioma xenograft D-54 MG. RESULTS: The combination of BCNU and CPT-11 showed the highest enhancement index (2.0-3.3) when BCNU was given on day 1 and CPT-11 was given on days 1-5 and 8-12. Delay of CPT-11 administration to day 3 or day 5 substantially decreased activity with enhancement indices of 1.6-1.8 and 0.6-1.0, respectively. Delay of BCNU administration to day 8 also reduced the CPT-11 activity with enhancement indices of 1.2-1.4. CONCLUSIONS: These results suggest that the presence of a BCNU-induced adduct or possibly crosslink prior to administration of CPT-11 is critical for enhanced activity. Although the mechanism of this enhancement is not currently known, a phase I trial of CPT-11 plus BCNU for adults with recurrent malignant glioma based on these results is in progress.

Full Text

Duke Authors

Cited Authors

  • Castellino, RC; Elion, GB; Keir, ST; Houghton, PJ; Johnson, SP; Bigner, DD; Friedman, HS

Published Date

  • 2000

Published In

Volume / Issue

  • 45 / 4

Start / End Page

  • 345 - 349

PubMed ID

  • 10755324

International Standard Serial Number (ISSN)

  • 0344-5704

Digital Object Identifier (DOI)

  • 10.1007/s002800050050

Language

  • eng

Conference Location

  • Germany