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

Publication ,  Journal Article
Patel, VJ; Elion, GB; Houghton, PJ; Keir, S; Pegg, AE; Johnson, SP; Dolan, ME; Bigner, DD; Friedman, HS
Published in: Clin Cancer Res
October 2000

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.

Duke Scholars

Published In

Clin Cancer Res

ISSN

1078-0432

Publication Date

October 2000

Volume

6

Issue

10

Start / End Page

4154 / 4157

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Time Factors
  • Temozolomide
  • Oncology & Carcinogenesis
  • Nervous System Neoplasms
  • Neoplasm Transplantation
  • Mice, Inbred BALB C
  • Mice
  • Male
  • Irinotecan
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Patel, V. J., Elion, G. B., Houghton, P. J., Keir, S., Pegg, A. E., Johnson, S. P., … Friedman, H. S. (2000). Schedule-dependent activity of temozolomide plus CPT-11 against a human central nervous system tumor-derived xenograft. Clin Cancer Res, 6(10), 4154–4157.
Patel, V. J., G. B. Elion, P. J. Houghton, S. Keir, A. E. Pegg, S. P. Johnson, M. E. Dolan, D. D. Bigner, and H. S. Friedman. “Schedule-dependent activity of temozolomide plus CPT-11 against a human central nervous system tumor-derived xenograft.Clin Cancer Res 6, no. 10 (October 2000): 4154–57.
Patel VJ, Elion GB, Houghton PJ, Keir S, Pegg AE, Johnson SP, et al. Schedule-dependent activity of temozolomide plus CPT-11 against a human central nervous system tumor-derived xenograft. Clin Cancer Res. 2000 Oct;6(10):4154–7.
Patel, V. J., et al. “Schedule-dependent activity of temozolomide plus CPT-11 against a human central nervous system tumor-derived xenograft.Clin Cancer Res, vol. 6, no. 10, Oct. 2000, pp. 4154–57.
Patel VJ, Elion GB, Houghton PJ, Keir S, Pegg AE, Johnson SP, Dolan ME, Bigner DD, Friedman HS. Schedule-dependent activity of temozolomide plus CPT-11 against a human central nervous system tumor-derived xenograft. Clin Cancer Res. 2000 Oct;6(10):4154–4157.

Published In

Clin Cancer Res

ISSN

1078-0432

Publication Date

October 2000

Volume

6

Issue

10

Start / End Page

4154 / 4157

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Time Factors
  • Temozolomide
  • Oncology & Carcinogenesis
  • Nervous System Neoplasms
  • Neoplasm Transplantation
  • Mice, Inbred BALB C
  • Mice
  • Male
  • Irinotecan