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Phase II trial of temozolomide plus o6-benzylguanine in adults with recurrent, temozolomide-resistant 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: J Clin Oncol
March 10, 2009

PURPOSE: This phase II trial was designed to define the role of O(6)-benzylguanine (O(6)-BG) in restoring temozolomide sensitivity in patients with recurrent or progressive, temozolomide-resistant malignant glioma and to evaluate the safety of administering O(6)-BG in combination with temozolomide. PATIENTS AND METHODS: Patients were accrued into two independent strata on the basis of histology: glioblastoma multiforme (GBM) and anaplastic glioma. Both temozolomide and O(6)-BG were administered on day 1 of a 28-day treatment cycle. Patients were administered a 1-hour O(6)-BG infusion at a dose of 120 mg/m(2) followed immediately by a 48-hour infusion at a dose of 30 mg/m(2)/d. Temozolomide was administered orally within 60 minutes of the end of the 1-hour O(6)-BG infusion at a dose of 472 mg/m(2). The primary end point was objective response rate. Secondary end points included progression-free survival, overall survival, and safety. RESULTS: Sixty-six of 67 patients who enrolled were treated with temozolomide and O(6)-BG. One of 34 patients (3%) with GBM (95% CI, 0.1% to 15%) and five of 32 assessable patients (16%) with anaplastic glioma (95% CI, 5% to 33%) were responders. The most commonly reported adverse events were grade 4 hematologic events experienced in 48% of the patients. CONCLUSION: O(6)-BG when added to a 1-day dosing regimen of temozolomide was able to restore temozolomide sensitivity in patients with temozolomide-resistant anaplastic glioma, but there seemed to be no significant restoration of temozolomide sensitivity in patients with temozolomide-resistant GBM.

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Published In

J Clin Oncol

DOI

EISSN

1527-7755

Publication Date

March 10, 2009

Volume

27

Issue

8

Start / End Page

1262 / 1267

Location

United States

Related Subject Headings

  • Temozolomide
  • Oncology & Carcinogenesis
  • Neoplasm Recurrence, Local
  • Middle Aged
  • Male
  • Humans
  • Guanine
  • Glioma
  • Female
  • Drug Resistance, Neoplasm
 

Citation

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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 II trial of temozolomide plus o6-benzylguanine in adults with recurrent, temozolomide-resistant malignant glioma. J Clin Oncol, 27(8), 1262–1267. https://doi.org/10.1200/JCO.2008.18.8417
Quinn, Jennifer A., Sara Xiaoyin Jiang, David A. Reardon, Annick Desjardins, James J. Vredenburgh, Jeremy N. Rich, Sridharan Gururangan, et al. “Phase II trial of temozolomide plus o6-benzylguanine in adults with recurrent, temozolomide-resistant malignant glioma.J Clin Oncol 27, no. 8 (March 10, 2009): 1262–67. https://doi.org/10.1200/JCO.2008.18.8417.
Quinn JA, Jiang SX, Reardon DA, Desjardins A, Vredenburgh JJ, Rich JN, et al. Phase II trial of temozolomide plus o6-benzylguanine in adults with recurrent, temozolomide-resistant malignant glioma. J Clin Oncol. 2009 Mar 10;27(8):1262–7.
Quinn, Jennifer A., et al. “Phase II trial of temozolomide plus o6-benzylguanine in adults with recurrent, temozolomide-resistant malignant glioma.J Clin Oncol, vol. 27, no. 8, Mar. 2009, pp. 1262–67. Pubmed, doi:10.1200/JCO.2008.18.8417.
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 II trial of temozolomide plus o6-benzylguanine in adults with recurrent, temozolomide-resistant malignant glioma. J Clin Oncol. 2009 Mar 10;27(8):1262–1267.

Published In

J Clin Oncol

DOI

EISSN

1527-7755

Publication Date

March 10, 2009

Volume

27

Issue

8

Start / End Page

1262 / 1267

Location

United States

Related Subject Headings

  • Temozolomide
  • Oncology & Carcinogenesis
  • Neoplasm Recurrence, Local
  • Middle Aged
  • Male
  • Humans
  • Guanine
  • Glioma
  • Female
  • Drug Resistance, Neoplasm