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Journal of Neuro-Oncology

, Volume 106, Issue 3, pp 643–649 | Cite as

A phase II study of O6-benzylguanine and temozolomide in pediatric patients with recurrent or progressive high-grade gliomas and brainstem gliomas: a Pediatric Brain Tumor Consortium study

  • Katherine E. WarrenEmail author
  • 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
Clinical Study - Patient Study

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 O6-benzylguanine (O6BG) and temozolomide® (TMZ). Patients received O6BG 120 mg/m2/d IV followed by TMZ 75 mg/m2/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 long-term 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.

Keywords

Glioma Pediatric Resistance Alkylating agent Brainstem glioma AGT MGMT 

Notes

Acknowledgments

This work was supported in part by NIH grant U01 CA81457 for the Pediatric Brain Tumor Consortium, NIH grant 5M01RR000188, and the American Lebanese Syrian Associated Charities, and the intramural program of the NIH. The authors and the PBTC acknowledge the protocol management of Mr. Christopher Smith, the central pathology review participation of Dr. Adesina Adekunle and Dr. Veena Rajaram and the statistical support of Mr. Shawn Lesh.

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Copyright information

© Springer Science+Business Media, LLC. (outside the USA) 2011

Authors and Affiliations

  • Katherine E. Warren
    • 1
    Email author
  • Sri Gururangan
    • 2
  • J. Russell Geyer
    • 3
  • Roger E. McLendon
    • 2
  • Tina Young Poussaint
    • 4
  • Dana Wallace
    • 11
  • Frank M. Balis
    • 8
  • Stacey L. Berg
    • 5
  • Roger J. Packer
    • 6
  • Stewart Goldman
    • 7
  • Jane E. Minturn
    • 8
  • Ian F. Pollack
    • 9
  • James M. Boyett
    • 11
  • Larry E. Kun
    • 10
  1. 1.Pediatric Oncology BranchNational Cancer InstituteBethesdaUSA
  2. 2.Duke University Medical CenterDurhamUSA
  3. 3.Seattle Children’s HospitalSeattleUSA
  4. 4.Children’s Hospital, BostonBostonUSA
  5. 5.Texas Children’s Cancer CenterHoustonUSA
  6. 6.Children’s National Medical CenterWashingtonUSA
  7. 7.Children’s Memorial HospitalChicagoUSA
  8. 8.Children’s Hospital of PhiladelphiaPhiladelphiaUSA
  9. 9.Children’s Hospital of PittsburghPittsburghUSA
  10. 10.St. Jude Children’s Research HospitalMemphisUSA
  11. 11.Operations and Biostatistics Center for the Pediatric Brain Tumor ConsortiumMemphisUSA

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