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

  • Clinical-patient studies
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Summary

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.

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Authors and Affiliations

  1. Baylor College of Medicine, 6621 Fannin, CC 1510.00, Houston, TX, USA

    Murali M. Chintagumpala, Charles McCluggage, Shiao Woo, Susan M. Blaney &  and Marc E. Horowitz

  2. Duke University Medical Center, Durham, NC, USA

    Henry S. Friedman, Roger E. McLendon & Paul L. Modrich

  3. St Jude Children’s Research Hospital, Memphis, TN, USA

    Clinton F. Stewart, Stephen Thompson & Larry E. Kun

  4. Children’s Oncology Group Operations Center, Arcadia, CA, USA

    James Kepner & Emi Holmes

  5. The Johns Hopkins Hospital, Baltimore, MD, USA

    Peter Burger

  6. Toronto Sick Children’s Hospital, Toronto, ON, USA

    James Rutka

  7. Washington University Medical School, St. Louis, MO, USA

    Jeff Michalski

  8. Baylor College of Medicine, 6621 Fannin, CC 1510.00, Houston, TX, USA

    Murali M. Chintagumpala

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  1. Murali M. Chintagumpala
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  2. Henry S. Friedman
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  3. Clinton F. Stewart
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  4. James Kepner
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  5. Roger E. McLendon
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  6. Paul L. Modrich
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  7. Charles McCluggage
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  8. Peter Burger
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  9. Emi Holmes
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  10. Stephen Thompson
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  11. James Rutka
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  12. Jeff Michalski
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  13. Shiao Woo
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  14. Susan M. Blaney
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  15. Larry E. Kun
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  16. and Marc E. Horowitz
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A Pediatric Oncology Group Study

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Correspondence to Murali M. Chintagumpala.

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Chintagumpala, M.M., Friedman, H.S., Stewart, C.F. et al. A phase II window trial of procarbazine and topotecan in children with high-grade glioma: a report from the children’s oncology group. J Neurooncol 77, 193–198 (2006). https://doi.org/10.1007/s11060-005-9024-x

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  • DOI: https://doi.org/10.1007/s11060-005-9024-x

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