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Antitumor activity of temozolomide combined with irinotecan is partly independent of O6-methylguanine-DNA methyltransferase and mismatch repair phenotypes in xenograft models.

Publication ,  Journal Article
Houghton, PJ; Stewart, CF; Cheshire, PJ; Richmond, LB; Kirstein, MN; Poquette, CA; Tan, M; Friedman, HS; Brent, TP
Published in: Clin Cancer Res
October 2000

The activity of temozolomide combined with irinotecan (CPT-11) was evaluated against eight independent xenografts (four neuroblastomas, three rhabdomyosarcomas, and one glioblastoma). In all studies, temozolomide was administered p.o. daily for 5 consecutive days/cycle, found in preliminary studies to be the optimal schedule for administration. Irinotecan was administered i.v. for 5 days for 2 consecutive weeks/cycle. Treatment cycles were repeated every 21 days for a total of three cycles over 8 weeks. In combination, temozolomide and CPT-11 induced complete responses in four neuroblastomas, two rhabdomyosarcomas, and the glioblastoma line. The activity of the combination was significantly greater than the activity of either agent administered alone in four tumor lines. Of interest, the interaction appeared independent of tumor MGMT or mismatch repair phenotype, suggesting that the mechanism of synergy may be independent of O6-methylation by temozolomide. Pharmacokinetic studies indicated no detectable interaction between these two agents. Further, coadministration of CPT-11 appeared to reduce the toxicity of temozolomide in tumor-bearing mice.

Duke Scholars

Published In

Clin Cancer Res

ISSN

1078-0432

Publication Date

October 2000

Volume

6

Issue

10

Start / End Page

4110 / 4118

Location

United States

Related Subject Headings

  • Time Factors
  • Temozolomide
  • Rhabdomyosarcoma
  • Phenotype
  • Oncology & Carcinogenesis
  • O(6)-Methylguanine-DNA Methyltransferase
  • Neuroblastoma
  • Neoplasm Transplantation
  • Mice, Inbred CBA
  • Mice
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Houghton, P. J., Stewart, C. F., Cheshire, P. J., Richmond, L. B., Kirstein, M. N., Poquette, C. A., … Brent, T. P. (2000). Antitumor activity of temozolomide combined with irinotecan is partly independent of O6-methylguanine-DNA methyltransferase and mismatch repair phenotypes in xenograft models. Clin Cancer Res, 6(10), 4110–4118.
Houghton, P. J., C. F. Stewart, P. J. Cheshire, L. B. Richmond, M. N. Kirstein, C. A. Poquette, M. Tan, H. S. Friedman, and T. P. Brent. “Antitumor activity of temozolomide combined with irinotecan is partly independent of O6-methylguanine-DNA methyltransferase and mismatch repair phenotypes in xenograft models.Clin Cancer Res 6, no. 10 (October 2000): 4110–18.
Houghton PJ, Stewart CF, Cheshire PJ, Richmond LB, Kirstein MN, Poquette CA, et al. Antitumor activity of temozolomide combined with irinotecan is partly independent of O6-methylguanine-DNA methyltransferase and mismatch repair phenotypes in xenograft models. Clin Cancer Res. 2000 Oct;6(10):4110–8.
Houghton PJ, Stewart CF, Cheshire PJ, Richmond LB, Kirstein MN, Poquette CA, Tan M, Friedman HS, Brent TP. Antitumor activity of temozolomide combined with irinotecan is partly independent of O6-methylguanine-DNA methyltransferase and mismatch repair phenotypes in xenograft models. Clin Cancer Res. 2000 Oct;6(10):4110–4118.

Published In

Clin Cancer Res

ISSN

1078-0432

Publication Date

October 2000

Volume

6

Issue

10

Start / End Page

4110 / 4118

Location

United States

Related Subject Headings

  • Time Factors
  • Temozolomide
  • Rhabdomyosarcoma
  • Phenotype
  • Oncology & Carcinogenesis
  • O(6)-Methylguanine-DNA Methyltransferase
  • Neuroblastoma
  • Neoplasm Transplantation
  • Mice, Inbred CBA
  • Mice