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

doi:10.1007/s11060-011-0709-z

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

^*Corresponding author for this work

Pediatrics

Research output: Contribution to journal › Article › peer-review

61 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 language	English (US)
Pages (from-to)	643-649
Number of pages	7
Journal	Journal of Neuro-Oncology
Volume	106
Issue number	3
DOIs	https://doi.org/10.1007/s11060-011-0709-z
State	Published - Feb 2012

Funding

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.

Keywords

AGT
Alkylating agent
Brainstem glioma
Glioma
MGMT
Pediatric
Resistance

ASJC Scopus subject areas

Clinical Neurology
Neurology
Oncology
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1007/s11060-011-0709-z

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

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title = "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",

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 {\textregistered} (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.",

keywords = "AGT, Alkylating agent, Brainstem glioma, Glioma, MGMT, Pediatric, Resistance",

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

note = "Funding Information: 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.",

year = "2012",

month = feb,

doi = "10.1007/s11060-011-0709-z",

language = "English (US)",

volume = "106",

pages = "643--649",

journal = "Journal of Neuro-Oncology",

issn = "0167-594X",

publisher = "Springer",

number = "3",

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Warren, KE, Gururangan, S, Geyer, JR, McLendon, RE, Poussaint, TY, Wallace, D, Balis, FM, Berg, SL, Packer, RJ, Goldman, S, Minturn, JE, Pollack, IF, Boyett, JM & Kun, LE 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, vol. 106, no. 3, pp. 643-649. https://doi.org/10.1007/s11060-011-0709-z

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. / Warren, Katherine E.; Gururangan, Sri; Geyer, J. Russell et al.
In: Journal of Neuro-Oncology, Vol. 106, No. 3, 02.2012, p. 643-649.

Research output: Contribution to journal › Article › peer-review

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T2 - A Pediatric Brain Tumor Consortium study

AU - Warren, Katherine E.

AU - Gururangan, Sri

AU - Geyer, J. Russell

AU - McLendon, Roger E.

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AU - Wallace, Dana

AU - Balis, Frank M.

AU - Berg, Stacey L.

AU - Packer, Roger J.

AU - Goldman, Stewart

AU - Minturn, Jane E.

AU - Pollack, Ian F.

AU - Boyett, James M.

AU - Kun, Larry E.

N1 - Funding Information: 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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