Schedule-dependent activity of temozolomide plus CPT-11 against a human central nervous system tumor-derived xenograft

Vikas J. Patel, Gertrude B. Elion, Peter J. Houghton, Stephen Keir, Anthony Pegg, Stewart P. Johnson, M. Eileen Dolan, Darell D. Bigner, Henry S. Friedman

Research output: Contribution to journalArticle

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Abstract

Temozolomide, an imidazole tetrazinone, and CPT-11, a camptothecin derivative, have previously been shown to have anti-central nervous system tumor activity in laboratory and clinical studies. The current experiments were designed to evaluate the activity of temozolomide plus CPT-11 against a malignant glioma-derived xenograft, D-54 MG, growing s.c. in athymic nude mice. The initial schedule of i.p. drug administration was temozolomide at 0.1 LD10 on day 1 and CPT-11 at 0.1 LD10 on days 1-5 and 8-14. The combination of these two agents produced greater than additive activity against D-54 MG. This enhanced activity was maintained when the initial administration of CPT-11 was delayed to day 3 or day 5. However, when CPT-11 was administered first on day 1 using 0.5 LD10 (for the single dose schedule) followed by temozolomide (0.1 LD10) 5 h, 3 days, or 5 days later, the enhancement of activity was substantially reduced. These results demonstrate that the combination of temozolomide plus CPT-11 displays a schedule-dependent enhancement of antitumor activity, suggest a mechanistic explanation for the enhanced activity, and provide the rationale for a Phase I trial of this regimen.

Original languageEnglish (US)
Pages (from-to)4154-4157
Number of pages4
JournalClinical Cancer Research
Volume6
Issue number10
StatePublished - Jan 1 2000

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irinotecan
temozolomide
Central Nervous System Neoplasms
Heterografts
Appointments and Schedules
Nude Mice
Drug Administration Schedule
Camptothecin
Glioma

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Patel, V. J., Elion, G. B., Houghton, P. J., Keir, S., Pegg, A., Johnson, S. P., ... Friedman, H. S. (2000). Schedule-dependent activity of temozolomide plus CPT-11 against a human central nervous system tumor-derived xenograft. Clinical Cancer Research, 6(10), 4154-4157.
Patel, Vikas J. ; Elion, Gertrude B. ; Houghton, Peter J. ; Keir, Stephen ; Pegg, Anthony ; Johnson, Stewart P. ; Dolan, M. Eileen ; Bigner, Darell D. ; Friedman, Henry S. / Schedule-dependent activity of temozolomide plus CPT-11 against a human central nervous system tumor-derived xenograft. In: Clinical Cancer Research. 2000 ; Vol. 6, No. 10. pp. 4154-4157.
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Patel, VJ, Elion, GB, Houghton, PJ, Keir, S, Pegg, A, Johnson, SP, Dolan, ME, Bigner, DD & Friedman, HS 2000, 'Schedule-dependent activity of temozolomide plus CPT-11 against a human central nervous system tumor-derived xenograft', Clinical Cancer Research, vol. 6, no. 10, pp. 4154-4157.

Schedule-dependent activity of temozolomide plus CPT-11 against a human central nervous system tumor-derived xenograft. / Patel, Vikas J.; Elion, Gertrude B.; Houghton, Peter J.; Keir, Stephen; Pegg, Anthony; Johnson, Stewart P.; Dolan, M. Eileen; Bigner, Darell D.; Friedman, Henry S.

In: Clinical Cancer Research, Vol. 6, No. 10, 01.01.2000, p. 4154-4157.

Research output: Contribution to journalArticle

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AU - Patel, Vikas J.

AU - Elion, Gertrude B.

AU - Houghton, Peter J.

AU - Keir, Stephen

AU - Pegg, Anthony

AU - Johnson, Stewart P.

AU - Dolan, M. Eileen

AU - Bigner, Darell D.

AU - Friedman, Henry S.

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