A phase II window trial of procarbazine and topotecan in children with high-grade glioma: A report from the children's oncology group

Murali M. Chintagumpala, Henry S. Friedman, Clinton F. Stewart, James Kepner, Roger E. McLendon, Paul L. Modrich, Charles McCluggage, Peter Burger, Emi Holmes, Stephen Thompson, James Rutka, Jeff Michalski, Shiao Woo, Susan M. Blaney, Larry E. Kun, Marc E. Horowitz

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

The role of chemotherapy in the treatment of high-grade gliomas in children is unclear. Early reports were suggestive of improved outcome in children with high-grade glioma with the addition of chemotherapy after surgery and radiation therapy. Subsequent studies did not show similar favorable contribution of chemotherapy to the outcome of these children. Further efforts to identify active chemotherapy agents in children include use of agents that have shown efficacy in adult patients with high-grade glioma and agents that have shown promise in mice bearing human xenografts of brain tumors. A Pediatric Oncology Group (POG 9431) trial tested the activity of two such agents, procarbazine and topotecan in newly diagnosed patients with high-grade glioma who had measurable disease after diagnostic surgery. Neither agent showed efficacy within the confines of the statistical design of the study. This study showed that children with high-grade glioma have an innate resistance to alkylating agents based on mismatch repair deficiency and high levels of alkyguanine transferase (AGT). Future trials should consider strategies to overcome the resistance mechanisms in children with high-grade glioma.

Original languageEnglish (US)
Pages (from-to)193-198
Number of pages6
JournalJournal of Neuro-Oncology
Volume77
Issue number2
DOIs
StatePublished - Apr 1 2006

Keywords

  • AGT activity in high-grade glioma in children
  • High-grade glioma in children
  • Mismatch repair proteins in high-grade glioma in children
  • Phase II window therapy in high-grade glioma in children
  • Procarbazine in high-grade glioma in children
  • Resistance mechanisms in high-grade glioma in children
  • Topotecan in high-grade glioma in children

ASJC Scopus subject areas

  • Oncology
  • Neurology
  • Clinical Neurology
  • Cancer Research

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    Chintagumpala, M. M., Friedman, H. S., Stewart, C. F., Kepner, J., McLendon, R. E., Modrich, P. L., McCluggage, C., Burger, P., Holmes, E., Thompson, S., Rutka, J., Michalski, J., Woo, S., Blaney, S. M., Kun, L. E., & Horowitz, M. E. (2006). A phase II window trial of procarbazine and topotecan in children with high-grade glioma: A report from the children's oncology group. Journal of Neuro-Oncology, 77(2), 193-198. https://doi.org/10.1007/s11060-005-9024-x