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Phase I trial of temozolomide plus O6-benzylguanine for patients with recurrent or progressive malignant glioma.

Publication ,  Journal Article
Quinn, JA; Desjardins, A; Weingart, J; Brem, H; Dolan, ME; Delaney, SM; Vredenburgh, J; Rich, J; Friedman, AH; Reardon, DA; Sampson, JH ...
Published in: J Clin Oncol
October 1, 2005

PURPOSE: We conducted a two-phase clinical trial in patients with progressive malignant glioma (MG). The first phase of this trial was designed to determine the dose of O6-BG effective in producing complete depletion of tumor AGT activity for 48 hours. The second phase of the trial was designed to define the maximum tolerated dose (MTD) of a single dose of temozolomide when combined with O6-BG. In addition, plasma concentrations of O6-BG and O6-benzyl-8-oxoguanine were evaluated after O6-BG. PATIENTS AND METHODS: For our first phase of the clinical trial, patients were scheduled to undergo craniotomy for AGT determination after receiving a 1-hour O6-BG infusion at 120 mg/m2 followed by a continuous infusion at an initial dose of 30 mg/m2/d for 48 hours. The dose of the continuous infusion of O6-BG escalated until tumor AGT was depleted. Once the O6-BG dose was established a separate group of patients was enrolled in the second phase of clinical trial, in which temozolomide, administered as a single dose at the end of the 1-hour O6-BG infusion, was escalated until the MTD was determined. RESULTS: The O6-BG dose found to be effective in depleting tumor AGT activity at 48 hours was an IV bolus of 120 mg/m2 over 1 hour followed by a continuous infusion of 30 mg/m2/d for 48 hours. On enrolling 38 patients in six dose levels of temozolomide, the MTD was established at 472 mg/m2 with dose-limiting toxicities limited to myelosuppression. CONCLUSION: This study provides the foundation for a phase II trial of O6-BG plus temozolomide in temozolomide-resistant MG.

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Published In

J Clin Oncol

DOI

ISSN

0732-183X

Publication Date

October 1, 2005

Volume

23

Issue

28

Start / End Page

7178 / 7187

Location

United States

Related Subject Headings

  • Temozolomide
  • Oncology & Carcinogenesis
  • Middle Aged
  • Maximum Tolerated Dose
  • Male
  • Injections, Intravenous
  • Infusions, Intravenous
  • Humans
  • Guanine
  • Glioma
 

Citation

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Quinn, J. A., Desjardins, A., Weingart, J., Brem, H., Dolan, M. E., Delaney, S. M., … Friedman, H. S. (2005). Phase I trial of temozolomide plus O6-benzylguanine for patients with recurrent or progressive malignant glioma. J Clin Oncol, 23(28), 7178–7187. https://doi.org/10.1200/JCO.2005.06.502
Quinn, Jennifer A., Annick Desjardins, Jon Weingart, Henry Brem, M Eileen Dolan, Shannon M. Delaney, James Vredenburgh, et al. “Phase I trial of temozolomide plus O6-benzylguanine for patients with recurrent or progressive malignant glioma.J Clin Oncol 23, no. 28 (October 1, 2005): 7178–87. https://doi.org/10.1200/JCO.2005.06.502.
Quinn JA, Desjardins A, Weingart J, Brem H, Dolan ME, Delaney SM, et al. Phase I trial of temozolomide plus O6-benzylguanine for patients with recurrent or progressive malignant glioma. J Clin Oncol. 2005 Oct 1;23(28):7178–87.
Quinn, Jennifer A., et al. “Phase I trial of temozolomide plus O6-benzylguanine for patients with recurrent or progressive malignant glioma.J Clin Oncol, vol. 23, no. 28, Oct. 2005, pp. 7178–87. Pubmed, doi:10.1200/JCO.2005.06.502.
Quinn JA, Desjardins A, Weingart J, Brem H, Dolan ME, Delaney SM, Vredenburgh J, Rich J, Friedman AH, Reardon DA, Sampson JH, Pegg AE, Moschel RC, Birch R, McLendon RE, Provenzale JM, Gururangan S, Dancey JE, Maxwell J, Tourt-Uhlig S, Herndon JE, Bigner DD, Friedman HS. Phase I trial of temozolomide plus O6-benzylguanine for patients with recurrent or progressive malignant glioma. J Clin Oncol. 2005 Oct 1;23(28):7178–7187.

Published In

J Clin Oncol

DOI

ISSN

0732-183X

Publication Date

October 1, 2005

Volume

23

Issue

28

Start / End Page

7178 / 7187

Location

United States

Related Subject Headings

  • Temozolomide
  • Oncology & Carcinogenesis
  • Middle Aged
  • Maximum Tolerated Dose
  • Male
  • Injections, Intravenous
  • Infusions, Intravenous
  • Humans
  • Guanine
  • Glioma