A phase II study of O 6-benzylguanine and temozolomide in pediatric patients with recurrent or progressive high-grade gliomas and brainstem gliomas: A Pediatric Brain Tumor Consortium study

Katherine E. Warren, Sri Gururangan, J. Russell Geyer, Roger E. McLendon, Tina Young Poussaint, Dana Wallace, Frank M. Balis, Stacey L. Berg, Roger J. Packer, Stewart Goldman, Jane E. Minturn, Ian F. Pollack, James M. Boyett, Larry E. Kun

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40 Scopus citations

Abstract

To estimate the sustained (≥8 weeks) objective response rate in pediatric patients with recurrent or progressive high-grade gliomas (HGG, Stratum A) or brainstem gliomas (BSG, Stratum B) treated with the combination of O 6-benzylguanine (O6BG) and temozolomide ® (TMZ). Patients received O6BG 120 mg/m 2/d IV followed by TMZ 75 mg/m 2/d orally daily for 5 consecutive days of each 28-day course. The target objective response rate to consider the combination active was 17%. A two-stage design was employed. Forty-three patients were enrolled; 41 were evaluable for response, including 25 patients with HGG and 16 patients with BSG. The combination of O6BG and TMZ was tolerable, and the primary toxicities were myelosuppression and gastrointestinal symptoms. One sustained (≥8 weeks) partial response was observed in the HGG cohort; no sustained objective responses were observed in the BSG cohort. Long-term (≥6 courses) stable disease (SD) was observed in 4 patients in Stratum A and 1 patient in Stratum B. Of the 5 patients with objective response or longterm SD, 3 underwent central review with 2 reclassified as low-grade gliomas. The combination of O6BG and TMZ did not achieve the target response rate for activity in pediatric patients with recurrent or progressive HGG and BSG.

Original languageEnglish (US)
Pages (from-to)643-649
Number of pages7
JournalJournal of Neuro-Oncology
Volume106
Issue number3
DOIs
StatePublished - Feb 1 2012

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Keywords

  • AGT
  • Alkylating agent
  • Brainstem glioma
  • Glioma
  • MGMT
  • Pediatric
  • Resistance

ASJC Scopus subject areas

  • Oncology
  • Neurology
  • Clinical Neurology
  • Cancer Research

Cite this

Warren, K. E., Gururangan, S., Geyer, J. R., McLendon, R. E., Poussaint, T. Y., Wallace, D., Balis, F. M., Berg, S. L., Packer, R. J., Goldman, S., Minturn, J. E., Pollack, I. F., Boyett, J. M., & Kun, L. E. (2012). A phase II study of O 6-benzylguanine and temozolomide in pediatric patients with recurrent or progressive high-grade gliomas and brainstem gliomas: A Pediatric Brain Tumor Consortium study. Journal of Neuro-Oncology, 106(3), 643-649. https://doi.org/10.1007/s11060-011-0709-z