Phase II trial of 7 days on/7 days off temozolmide for recurrent high-grade glioma

Seunggu J. Han, John D. Rolston, Annette M. Molinaro, Jennifer L. Clarke, Michael D. Prados, Susan M. Chang, Mitchel S. Berger, Ashley DeSilva, Nicholas A. Butowski

Research output: Contribution to journalArticle

28 Scopus citations

Abstract

Background. A phase II trial was performed to evaluate the efficacy of a dose-dense, 7 days on/7 days off schedule of temozolomide for patients with recurrent high-grade gliomas (HGG). Methods. Sixty patients with recurrent HGG received temozolomide at 150 mg/m2/day on days 1-7 and days 15-21 during each 4-week cycle. The primary endpoint was 6-month progression-free survival (PFS-6), with a secondary endpoint of overall survival (OS). A further exploratory objective included the investigation of whether methylation status of the O(6)-methylguanine-DNA methyltransferase (MGMT) promoter within tumor tissue predicted outcomes. Results. Among patients with glioblastoma (n = 40), PFS-6 was 10% (95% CI, 3%-24%) with median OS of 21.6 weeks (95% CI, 16.9-30.6 weeks). PFS-6 for grade III glioma patients (n = 20) was 50% (95% CI, 27%-73%), and median OS was 100.6 weeks (95% CI, 67 weeks to not reached). There were trends towards longer PFS and OS with MGMT promoter methylation (log-rank test; P = .06 for PFS; P = .07 for OS). Additionally, bevacizumab-naïve glioblastoma patients had significantly longer PFS and OS (median PFS was 8.07 weeks [95% CI, 8 weeks to not reached] vs 7.57 weeks [95% CI, 7.29-8.29 weeks], log-rank test, P < .001; median OS was 62 weeks [26.1 weeks to not reached] vs 18.2 weeks [13.9-27.3 weeks], log-rank test, P < .001). Conclusions. The dose-dense temozolomide regimen was well tolerated, although it has no significant activity in this population. Clinical trials.gov identified. NCT00619112 (available at http://clinicaltrials.gov/ct2/show/NCT00619112).

Original languageEnglish (US)
Pages (from-to)1255-1262
Number of pages8
JournalNeuro-Oncology
Volume16
Issue number9
DOIs
StatePublished - Sep 2014

Keywords

  • Bevacizumab
  • Chemotherapy
  • Glioblastoma
  • Glioma
  • Temozolomide.

ASJC Scopus subject areas

  • Oncology
  • Clinical Neurology
  • Cancer Research

Fingerprint Dive into the research topics of 'Phase II trial of 7 days on/7 days off temozolmide for recurrent high-grade glioma'. Together they form a unique fingerprint.

  • Cite this

    Han, S. J., Rolston, J. D., Molinaro, A. M., Clarke, J. L., Prados, M. D., Chang, S. M., Berger, M. S., DeSilva, A., & Butowski, N. A. (2014). Phase II trial of 7 days on/7 days off temozolmide for recurrent high-grade glioma. Neuro-Oncology, 16(9), 1255-1262. https://doi.org/10.1093/neuonc/nou044