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

Henry S. Friedman, Robert C. Castellino, Gertrude B. Elion, Stephen T. Keir, Peter J. Houghton, Stewart P. Johnson, Darell D. Bigner

Research output: Contribution to journalArticlepeer-review

29 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)345-349
Number of pages5
JournalCancer chemotherapy and pharmacology
Issue number4
StatePublished - 2000
Externally publishedYes


  • CPT-11
  • Glioma
  • Nitrosourea

ASJC Scopus subject areas

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


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