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Updated: Aug 4, 2026
Establishing Intracranial Brain Tumor Xenografts With Subsequent Analysis of Tumor Growth and Response to Therapy using Bioluminescence Imaging
Published on: July 13, 2010
Schedule-dependent activity of irinotecan plus BCNU against malignant glioma xenografts
R C Castellino1, G B Elion, S T Keir
1Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA.
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.
