Skip to main content
Journal cover image

Phase 1 trial of temozolomide plus irinotecan plus O6-benzylguanine in adults with recurrent malignant glioma.

Publication ,  Journal Article
Quinn, JA; Jiang, SX; Reardon, DA; Desjardins, A; Vredenburgh, JJ; Gururangan, S; Sampson, JH; McLendon, RE; Herndon, JE; Friedman, HS
Published in: Cancer
July 1, 2009

BACKGROUND: The current study was a phase 1 clinical trial conducted with patients who had recurrent or progressive malignant glioma (MG). The trial was designed to determine the maximum tolerated dose (MTD) and toxicity of irinotecan (CPT-11) when administered with temozolomide (TMZ) and O(6)-benzylguanine (O(6)-BG). METHODS: All 3 drugs, CPT-11, TMZ, and O(6)-BG, were administered on Day 1 of a 21-day treatment. First, patients were treated with a 1-hour bolus infusion of O(6)-BG at a dose of 120 mg/m(2) followed immediately by a 48-hour continuous infusion of O(6)-BG at a dose of 30 mg/m(2)/d. Second, within 60 minutes of the end of the 1-hour bolus infusion of O(6)-BG, TMZ was administered orally at a dose of 355 mg/m(2). Third, 1 hour after administration of TMZ, CPT-11 was infused over 90 minutes. Patients were accrued to 1 of 2 strata based on CYP3A1- and CYP3A4-inducing antiepileptic drug (EIAED) use; dose escalation was conducted independently within these strata. RESULTS: Fifty-five patients were enrolled. In both strata, the dose-limiting toxicities were hematologic and included grade 4 neutropenia, febrile neutropenia, leukopenia, and/or thrombocytopenia. For Stratum 1 (EIAEDs), when TMZ was administered at a dose of 355 mg/m(2), the MTD of CPT-11 was determined to be 120 mg/m(2). In contrast, for Stratum 2 (no EIAEDs), when TMZ was administered at a dose of 200 mg/m(2), the MTD of CPT-11 was determined to be 80 mg/m(2). CONCLUSIONS: The authors believe that the results of the current study provide the foundation for a phase 2 trial of O(6)-BG in combination with CPT-11 and TMZ in patients with MG.

Duke Scholars

Published In

Cancer

DOI

ISSN

0008-543X

Publication Date

July 1, 2009

Volume

115

Issue

13

Start / End Page

2964 / 2970

Location

United States

Related Subject Headings

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

Citation

APA
Chicago
ICMJE
MLA
NLM
Quinn, J. A., Jiang, S. X., Reardon, D. A., Desjardins, A., Vredenburgh, J. J., Gururangan, S., … Friedman, H. S. (2009). Phase 1 trial of temozolomide plus irinotecan plus O6-benzylguanine in adults with recurrent malignant glioma. Cancer, 115(13), 2964–2970. https://doi.org/10.1002/cncr.24336
Quinn, Jennifer A., Sara Xiaoyin Jiang, David A. Reardon, Annick Desjardins, James J. Vredenburgh, Sridharan Gururangan, John H. Sampson, Roger E. McLendon, James E. Herndon, and Henry S. Friedman. “Phase 1 trial of temozolomide plus irinotecan plus O6-benzylguanine in adults with recurrent malignant glioma.Cancer 115, no. 13 (July 1, 2009): 2964–70. https://doi.org/10.1002/cncr.24336.
Quinn JA, Jiang SX, Reardon DA, Desjardins A, Vredenburgh JJ, Gururangan S, et al. Phase 1 trial of temozolomide plus irinotecan plus O6-benzylguanine in adults with recurrent malignant glioma. Cancer. 2009 Jul 1;115(13):2964–70.
Quinn, Jennifer A., et al. “Phase 1 trial of temozolomide plus irinotecan plus O6-benzylguanine in adults with recurrent malignant glioma.Cancer, vol. 115, no. 13, July 2009, pp. 2964–70. Pubmed, doi:10.1002/cncr.24336.
Quinn JA, Jiang SX, Reardon DA, Desjardins A, Vredenburgh JJ, Gururangan S, Sampson JH, McLendon RE, Herndon JE, Friedman HS. Phase 1 trial of temozolomide plus irinotecan plus O6-benzylguanine in adults with recurrent malignant glioma. Cancer. 2009 Jul 1;115(13):2964–2970.
Journal cover image

Published In

Cancer

DOI

ISSN

0008-543X

Publication Date

July 1, 2009

Volume

115

Issue

13

Start / End Page

2964 / 2970

Location

United States

Related Subject Headings

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