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Phase I trial of temozolomide plus O6-benzylguanine 5-day regimen with recurrent malignant glioma.

Publication ,  Journal Article
Quinn, JA; Jiang, SX; Reardon, DA; Desjardins, A; Vredenburgh, JJ; Rich, JN; Gururangan, S; Friedman, AH; Bigner, DD; Sampson, JH; McLendon, RE ...
Published in: Neuro Oncol
October 2009

This phase I clinical trial conducted with patients who had recurrent or progressive malignant glioma (MG) was designed to determine the maximum tolerated dose (MTD) and toxicity of three different 5-day dosing regimens of temozolomide (TMZ) in combination with O(6)-benzylguanine (O(6)-BG). Both TMZ and O(6)-BG were administered on days 1-5 of a 28-day treatment cycle. A bolus infusion of O(6)-BG was administered at 120 mg/m(2) over 1 h on days 1, 3, and 5, along with a continuous infusion of O(6)-BG at 30 mg/m(2)/day. TMZ was administered at the end of the first bolus infusion of O(6)-BG and then every 24 h for 5 days during the continuous infusion of O(6)-BG. Patients were accrued to one of three 5-day dosing regimens of TMZ. Twenty-nine patients were enrolled into this study. The dose-limiting toxicities (DLTs) were grade 4 neutropenia, leukopenia, and thrombocytopenia. The MTD for TMZ for the three different 5-day dosing schedules was determined as follows: schedule 1, 200 mg/m(2) on day 1 and 50 mg/m(2)/day on days 2-5; schedule 2, 50 mg/m(2)/day on days 1-5; and schedule 3, 50 mg/m(2)/day on days 1-5 while receiving pegfilgrastim. Thus, the 5-day TMZ dosing schedule that maximized the total dose of TMZ when combined with O(6)-BG was schedule 1. This study provides the foundation for a phase II trial of O(6)-BG in combination with a 5-day dosing schedule of TMZ in TMZ-resistant MG.

Duke Scholars

Published In

Neuro Oncol

DOI

ISSN

1522-8517

Publication Date

October 2009

Volume

11

Issue

5

Start / End Page

556 / 561

Location

England

Related Subject Headings

  • Treatment Outcome
  • Temozolomide
  • Oncology & Carcinogenesis
  • Neoplasm Recurrence, Local
  • Middle Aged
  • Maximum Tolerated Dose
  • Male
  • Humans
  • Guanine
  • Glioma
 

Citation

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MLA
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Quinn, J. A., Jiang, S. X., Reardon, D. A., Desjardins, A., Vredenburgh, J. J., Rich, J. N., … Friedman, H. S. (2009). Phase I trial of temozolomide plus O6-benzylguanine 5-day regimen with recurrent malignant glioma. Neuro Oncol, 11(5), 556–561. https://doi.org/10.1215/15228517-2009-007
Quinn, Jennifer A., Sara Xiaoyin Jiang, David A. Reardon, Annick Desjardins, James J. Vredenburgh, Jeremy N. Rich, Sridharan Gururangan, et al. “Phase I trial of temozolomide plus O6-benzylguanine 5-day regimen with recurrent malignant glioma.Neuro Oncol 11, no. 5 (October 2009): 556–61. https://doi.org/10.1215/15228517-2009-007.
Quinn JA, Jiang SX, Reardon DA, Desjardins A, Vredenburgh JJ, Rich JN, et al. Phase I trial of temozolomide plus O6-benzylguanine 5-day regimen with recurrent malignant glioma. Neuro Oncol. 2009 Oct;11(5):556–61.
Quinn, Jennifer A., et al. “Phase I trial of temozolomide plus O6-benzylguanine 5-day regimen with recurrent malignant glioma.Neuro Oncol, vol. 11, no. 5, Oct. 2009, pp. 556–61. Pubmed, doi:10.1215/15228517-2009-007.
Quinn JA, Jiang SX, Reardon DA, Desjardins A, Vredenburgh JJ, Rich JN, Gururangan S, Friedman AH, Bigner DD, Sampson JH, McLendon RE, Herndon JE, Walker A, Friedman HS. Phase I trial of temozolomide plus O6-benzylguanine 5-day regimen with recurrent malignant glioma. Neuro Oncol. 2009 Oct;11(5):556–561.
Journal cover image

Published In

Neuro Oncol

DOI

ISSN

1522-8517

Publication Date

October 2009

Volume

11

Issue

5

Start / End Page

556 / 561

Location

England

Related Subject Headings

  • Treatment Outcome
  • Temozolomide
  • Oncology & Carcinogenesis
  • Neoplasm Recurrence, Local
  • Middle Aged
  • Maximum Tolerated Dose
  • Male
  • Humans
  • Guanine
  • Glioma