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Phase II trial of Gliadel plus O6-benzylguanine in adults with recurrent glioblastoma multiforme.

Publication ,  Journal Article
Quinn, JA; Jiang, SX; Carter, J; Reardon, DA; Desjardins, A; Vredenburgh, JJ; Rich, JN; Gururangan, S; Friedman, AH; Bigner, DD; Sampson, JH ...
Published in: Clin Cancer Res
February 1, 2009

PURPOSE: This phase II trial was designed to define the efficacy of Gliadel wafers in combination with an infusion of O6-benzylguanine (O6-BG) that suppresses tumor O6-alkylguanine-DNA alkyltransferase (AGT) levels in patients with recurrent glioblastoma multiforme for 5 days and to evaluate the safety of this combination therapy. EXPERIMENTAL DESIGN: This was a phase II, open-label, single center trial. On gross total resection of the tumor, up to eight Gliadel wafers were implanted. Bolus infusion of O6-BG was administered at 120 mg/m2 over 1 hour on days 1, 3, and 5, along with a continuous infusion at 30 mg/m2/d. The primary end points were 6-month overall survival (OS) and safety, and the secondary end points were 1-year, 2-year, and median OS. RESULTS: Fifty-two patients were accrued. The 6-month OS was 82% [95% confidence interval (95% CI), 72-93%]. The 1- and 2-year OS rates were 47% (95% CI, 35-63%) and 10% (95% CI, 3-32%), respectively. The median OS was 50.3 weeks (95% CI, 36.1-69.4 weeks). Treatment-related toxicity with this drug combination included grade 3 hydrocephalus (9.6%), grade 3 cerebrospinal fluid (CSF) leak (19.2%), and grade 3 CSF/brain infection (13.4%). CONCLUSION: The efficacy of implanted Gliadel wafers may be improved with the addition of O6-BG. Although systemically administered O6-BG can be coadministered with Gliadel wafers safely, it may increase the risk of hydrocephalus, CSF leak, and CSF/brain infection. Future trials are required to verify that inhibition of tumor AGT levels by O6-BG results in increased efficacy of Gliadel wafers without added toxicity.

Duke Scholars

Published In

Clin Cancer Res

DOI

ISSN

1078-0432

Publication Date

February 1, 2009

Volume

15

Issue

3

Start / End Page

1064 / 1068

Location

United States

Related Subject Headings

  • Survival Analysis
  • Recurrence
  • Polyesters
  • Oncology & Carcinogenesis
  • O(6)-Methylguanine-DNA Methyltransferase
  • Middle Aged
  • Male
  • Humans
  • Guanine
  • Glioblastoma
 

Citation

APA
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MLA
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Quinn, J. A., Jiang, S. X., Carter, J., Reardon, D. A., Desjardins, A., Vredenburgh, J. J., … Friedman, H. S. (2009). Phase II trial of Gliadel plus O6-benzylguanine in adults with recurrent glioblastoma multiforme. Clin Cancer Res, 15(3), 1064–1068. https://doi.org/10.1158/1078-0432.CCR-08-2130
Quinn, Jennifer A., Sara Xiaoyin Jiang, James Carter, David A. Reardon, Annick Desjardins, James J. Vredenburgh, Jeremy N. Rich, et al. “Phase II trial of Gliadel plus O6-benzylguanine in adults with recurrent glioblastoma multiforme.Clin Cancer Res 15, no. 3 (February 1, 2009): 1064–68. https://doi.org/10.1158/1078-0432.CCR-08-2130.
Quinn JA, Jiang SX, Carter J, Reardon DA, Desjardins A, Vredenburgh JJ, et al. Phase II trial of Gliadel plus O6-benzylguanine in adults with recurrent glioblastoma multiforme. Clin Cancer Res. 2009 Feb 1;15(3):1064–8.
Quinn, Jennifer A., et al. “Phase II trial of Gliadel plus O6-benzylguanine in adults with recurrent glioblastoma multiforme.Clin Cancer Res, vol. 15, no. 3, Feb. 2009, pp. 1064–68. Pubmed, doi:10.1158/1078-0432.CCR-08-2130.
Quinn JA, Jiang SX, Carter J, Reardon DA, Desjardins A, Vredenburgh JJ, Rich JN, Gururangan S, Friedman AH, Bigner DD, Sampson JH, McLendon RE, Herndon JE, Threatt S, Friedman HS. Phase II trial of Gliadel plus O6-benzylguanine in adults with recurrent glioblastoma multiforme. Clin Cancer Res. 2009 Feb 1;15(3):1064–1068.

Published In

Clin Cancer Res

DOI

ISSN

1078-0432

Publication Date

February 1, 2009

Volume

15

Issue

3

Start / End Page

1064 / 1068

Location

United States

Related Subject Headings

  • Survival Analysis
  • Recurrence
  • Polyesters
  • Oncology & Carcinogenesis
  • O(6)-Methylguanine-DNA Methyltransferase
  • Middle Aged
  • Male
  • Humans
  • Guanine
  • Glioblastoma