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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

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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.

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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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Authors and Affiliations

  1. Pediatric Oncology Branch, National Cancer Institute, Building 10 CRC, Room 1-5750, Bethesda, MD, 20892, USA

    Katherine E. Warren

  2. Duke University Medical Center, Durham, USA

    Sri Gururangan & Roger E. McLendon

  3. Seattle Children’s Hospital, Seattle, USA

    J. Russell Geyer

  4. Children’s Hospital, Boston, Boston, USA

    Tina Young Poussaint

  5. Texas Children’s Cancer Center, Houston, USA

    Stacey L. Berg

  6. Children’s National Medical Center, Washington, USA

    Roger J. Packer

  7. Children’s Memorial Hospital, Chicago, USA

    Stewart Goldman

  8. Children’s Hospital of Philadelphia, Philadelphia, USA

    Frank M. Balis & Jane E. Minturn

  9. Children’s Hospital of Pittsburgh, Pittsburgh, USA

    Ian F. Pollack

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

    Larry E. Kun

  11. Operations and Biostatistics Center for the Pediatric Brain Tumor Consortium, Memphis, TN, USA

    Dana Wallace & James M. Boyett

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  1. Katherine E. Warren
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  2. Sri Gururangan
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  3. J. Russell Geyer
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Correspondence to Katherine E. Warren.

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Warren, K.E., Gururangan, S., Geyer, J.R. et al. 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. J Neurooncol 106, 643–649 (2012). https://doi.org/10.1007/s11060-011-0709-z

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  • DOI: https://doi.org/10.1007/s11060-011-0709-z

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