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

Seunggu (Jude) 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

27 Citations (Scopus)

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 - Jan 1 2014
Externally publishedYes

Fingerprint

Glioma
temozolomide
Survival
Glioblastoma
Methylation
O(6)-Methylguanine-DNA Methyltransferase
Methyltransferases
Carcinogens
Disease-Free Survival
Appointments and Schedules
Clinical Trials
DNA
Population

Keywords

  • Bevacizumab
  • Chemotherapy
  • Glioblastoma
  • Glioma
  • Temozolomide.

ASJC Scopus subject areas

  • Oncology
  • Clinical Neurology
  • Cancer Research

Cite this

Han, S. J., Rolston, J. D., Molinaro, A. M., Clarke, J. L., Prados, M. D., Chang, S. M., ... 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

Phase II trial of 7 days on/7 days off temozolmide for recurrent high-grade glioma. / Han, Seunggu (Jude); Rolston, John D.; Molinaro, Annette M.; Clarke, Jennifer L.; Prados, Michael D.; Chang, Susan M.; Berger, Mitchel S.; DeSilva, Ashley; Butowski, Nicholas A.

In: Neuro-Oncology, Vol. 16, No. 9, 01.01.2014, p. 1255-1262.

Research output: Contribution to journalArticle

Han, SJ, Rolston, JD, Molinaro, AM, Clarke, JL, Prados, MD, Chang, SM, Berger, MS, DeSilva, A & Butowski, NA 2014, 'Phase II trial of 7 days on/7 days off temozolmide for recurrent high-grade glioma', Neuro-Oncology, vol. 16, no. 9, pp. 1255-1262. https://doi.org/10.1093/neuonc/nou044
Han SJ, Rolston JD, Molinaro AM, Clarke JL, Prados MD, Chang SM et al. Phase II trial of 7 days on/7 days off temozolmide for recurrent high-grade glioma. Neuro-Oncology. 2014 Jan 1;16(9):1255-1262. https://doi.org/10.1093/neuonc/nou044
Han, Seunggu (Jude) ; Rolston, John D. ; Molinaro, Annette M. ; Clarke, Jennifer L. ; Prados, Michael D. ; Chang, Susan M. ; Berger, Mitchel S. ; DeSilva, Ashley ; Butowski, Nicholas A. / Phase II trial of 7 days on/7 days off temozolmide for recurrent high-grade glioma. In: Neuro-Oncology. 2014 ; Vol. 16, No. 9. pp. 1255-1262.
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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-na{\"i}ve 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).",
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T1 - Phase II trial of 7 days on/7 days off temozolmide for recurrent high-grade glioma

AU - Han, Seunggu (Jude)

AU - Rolston, John D.

AU - Molinaro, Annette M.

AU - Clarke, Jennifer L.

AU - Prados, Michael D.

AU - Chang, Susan M.

AU - Berger, Mitchel S.

AU - DeSilva, Ashley

AU - Butowski, Nicholas A.

PY - 2014/1/1

Y1 - 2014/1/1

N2 - 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).

AB - 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).

KW - Bevacizumab

KW - Chemotherapy

KW - Glioblastoma

KW - Glioma

KW - Temozolomide.

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