Cancer Chemotherapy and Pharmacology

, Volume 45, Issue 4, pp 345–349 | Cite as

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
ORIGINAL ARTICLE

Abstract

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.

Key words Nitrosourea CPT-11 Glioma 

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Copyright information

© Springer-Verlag Berlin Heidelberg 2000

Authors and Affiliations

  • Henry S. Friedman
    • 1
  • Robert C. Castellino
    • 1
  • Gertrude B. Elion
    • 2
  • Stephen T. Keir
    • 1
  • Peter J. Houghton
    • 3
  • Stewart P. Johnson
    • 1
  • Darell D. Bigner
    • 1
  1. 1.Department of Surgery, Duke University Medical Center, Box 3624, South Hospital, Durham, NC 27710, USA Tel.: +1-919-684-5301; Fax: +1-919-684-6674US
  2. 2.Department of Pharmacology, Duke University Medical Center, Durham, North Carolina, USAUS
  3. 3.Department of Molecular Pharmacology, St. Jude Children's Research Hospital, Memphis, Tennessee, USAUS

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