Phase 2 study of BCNU and temozolomide for recurrent glioblastoma multiforme

North American brain tumor consortium study

Michael D. Prados, W. K.Alfred Yung, Howard A. Fine, Harry S. Greenberg, Larry Junck, Susan M. Chang, M. Kelly Nicholas, H. Ian Robins, Minesh P. Mehta, Karen L. Fink, Kurt Jaeckle, John Kuhn, Kenneth R. Hess, S. Clifford Schold

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Abstract

The purpose of this study was to evaluate the activity, measured in terms of progression-free survival (PFS) and response rates, of 1,3-bis(chloro-ethyl)-1-nitrosourea (BCNU) plus temozolomide in adult patients with recurrent glioblastoma multiforme. The phase 2 dose and schedule for this trial was BCNU 150 mg/m2 i.v. followed in 2 h by temozolomide 550 mg/m2 as a single oral dose. Treatment was repeated every 6 weeks for up to 8 cycles unless tumor progression was documented. The primary end point was PFS at 6 months (PFS-6). Response was a secondary end point, measured by MR imaging, neurological status, and steroid requirements prior to each 6-week cycle. The median age of eligible patients was 53, and 89.5% had no prior chemotherapy. All patients were evaluable for toxicity and time to progression. The PFS-6 was 21%. Overall survival was 68% at 6 months and 26% at 1 year. The MRI response for 36 patients was 2 partial responses, 2 minor responses, 19 cases of stable disease, and 13 immediate progressions. Median survival was 34 weeks, and median PFS was 11 weeks. Toxicity was primarily myelosuppression; no toxic deaths occurred. Historical phase 2 study data in this patient population show a PFS-6 of 15%. Recent data for use of temozolomide alone have shown a PFS-6 of 21%. We conclude that BCNU plus temozolomide when used in these doses and schedule has only modest activity, with significant toxicity, and appears to be no more effective than single-agent temozolomide.

Original languageEnglish (US)
Pages (from-to)33-37
Number of pages5
JournalNeuro-Oncology
Volume6
Issue number1
DOIs
StatePublished - Jan 1 2004

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temozolomide
Carmustine
Glioblastoma
Brain Neoplasms
Disease-Free Survival
Appointments and Schedules
Survival
Poisons

All Science Journal Classification (ASJC) codes

  • Oncology
  • Clinical Neurology
  • Cancer Research

Cite this

Prados, M. D., Yung, W. K. A., Fine, H. A., Greenberg, H. S., Junck, L., Chang, S. M., ... Schold, S. C. (2004). Phase 2 study of BCNU and temozolomide for recurrent glioblastoma multiforme: North American brain tumor consortium study. Neuro-Oncology, 6(1), 33-37. https://doi.org/10.1215/S1152851703000309
Prados, Michael D. ; Yung, W. K.Alfred ; Fine, Howard A. ; Greenberg, Harry S. ; Junck, Larry ; Chang, Susan M. ; Nicholas, M. Kelly ; Robins, H. Ian ; Mehta, Minesh P. ; Fink, Karen L. ; Jaeckle, Kurt ; Kuhn, John ; Hess, Kenneth R. ; Schold, S. Clifford. / Phase 2 study of BCNU and temozolomide for recurrent glioblastoma multiforme : North American brain tumor consortium study. In: Neuro-Oncology. 2004 ; Vol. 6, No. 1. pp. 33-37.
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abstract = "The purpose of this study was to evaluate the activity, measured in terms of progression-free survival (PFS) and response rates, of 1,3-bis(chloro-ethyl)-1-nitrosourea (BCNU) plus temozolomide in adult patients with recurrent glioblastoma multiforme. The phase 2 dose and schedule for this trial was BCNU 150 mg/m2 i.v. followed in 2 h by temozolomide 550 mg/m2 as a single oral dose. Treatment was repeated every 6 weeks for up to 8 cycles unless tumor progression was documented. The primary end point was PFS at 6 months (PFS-6). Response was a secondary end point, measured by MR imaging, neurological status, and steroid requirements prior to each 6-week cycle. The median age of eligible patients was 53, and 89.5{\%} had no prior chemotherapy. All patients were evaluable for toxicity and time to progression. The PFS-6 was 21{\%}. Overall survival was 68{\%} at 6 months and 26{\%} at 1 year. The MRI response for 36 patients was 2 partial responses, 2 minor responses, 19 cases of stable disease, and 13 immediate progressions. Median survival was 34 weeks, and median PFS was 11 weeks. Toxicity was primarily myelosuppression; no toxic deaths occurred. Historical phase 2 study data in this patient population show a PFS-6 of 15{\%}. Recent data for use of temozolomide alone have shown a PFS-6 of 21{\%}. We conclude that BCNU plus temozolomide when used in these doses and schedule has only modest activity, with significant toxicity, and appears to be no more effective than single-agent temozolomide.",
author = "Prados, {Michael D.} and Yung, {W. K.Alfred} and Fine, {Howard A.} and Greenberg, {Harry S.} and Larry Junck and Chang, {Susan M.} and Nicholas, {M. Kelly} and Robins, {H. Ian} and Mehta, {Minesh P.} and Fink, {Karen L.} and Kurt Jaeckle and John Kuhn and Hess, {Kenneth R.} and Schold, {S. Clifford}",
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Prados, MD, Yung, WKA, Fine, HA, Greenberg, HS, Junck, L, Chang, SM, Nicholas, MK, Robins, HI, Mehta, MP, Fink, KL, Jaeckle, K, Kuhn, J, Hess, KR & Schold, SC 2004, 'Phase 2 study of BCNU and temozolomide for recurrent glioblastoma multiforme: North American brain tumor consortium study', Neuro-Oncology, vol. 6, no. 1, pp. 33-37. https://doi.org/10.1215/S1152851703000309

Phase 2 study of BCNU and temozolomide for recurrent glioblastoma multiforme : North American brain tumor consortium study. / Prados, Michael D.; Yung, W. K.Alfred; Fine, Howard A.; Greenberg, Harry S.; Junck, Larry; Chang, Susan M.; Nicholas, M. Kelly; Robins, H. Ian; Mehta, Minesh P.; Fink, Karen L.; Jaeckle, Kurt; Kuhn, John; Hess, Kenneth R.; Schold, S. Clifford.

In: Neuro-Oncology, Vol. 6, No. 1, 01.01.2004, p. 33-37.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Phase 2 study of BCNU and temozolomide for recurrent glioblastoma multiforme

T2 - North American brain tumor consortium study

AU - Prados, Michael D.

AU - Yung, W. K.Alfred

AU - Fine, Howard A.

AU - Greenberg, Harry S.

AU - Junck, Larry

AU - Chang, Susan M.

AU - Nicholas, M. Kelly

AU - Robins, H. Ian

AU - Mehta, Minesh P.

AU - Fink, Karen L.

AU - Jaeckle, Kurt

AU - Kuhn, John

AU - Hess, Kenneth R.

AU - Schold, S. Clifford

PY - 2004/1/1

Y1 - 2004/1/1

N2 - The purpose of this study was to evaluate the activity, measured in terms of progression-free survival (PFS) and response rates, of 1,3-bis(chloro-ethyl)-1-nitrosourea (BCNU) plus temozolomide in adult patients with recurrent glioblastoma multiforme. The phase 2 dose and schedule for this trial was BCNU 150 mg/m2 i.v. followed in 2 h by temozolomide 550 mg/m2 as a single oral dose. Treatment was repeated every 6 weeks for up to 8 cycles unless tumor progression was documented. The primary end point was PFS at 6 months (PFS-6). Response was a secondary end point, measured by MR imaging, neurological status, and steroid requirements prior to each 6-week cycle. The median age of eligible patients was 53, and 89.5% had no prior chemotherapy. All patients were evaluable for toxicity and time to progression. The PFS-6 was 21%. Overall survival was 68% at 6 months and 26% at 1 year. The MRI response for 36 patients was 2 partial responses, 2 minor responses, 19 cases of stable disease, and 13 immediate progressions. Median survival was 34 weeks, and median PFS was 11 weeks. Toxicity was primarily myelosuppression; no toxic deaths occurred. Historical phase 2 study data in this patient population show a PFS-6 of 15%. Recent data for use of temozolomide alone have shown a PFS-6 of 21%. We conclude that BCNU plus temozolomide when used in these doses and schedule has only modest activity, with significant toxicity, and appears to be no more effective than single-agent temozolomide.

AB - The purpose of this study was to evaluate the activity, measured in terms of progression-free survival (PFS) and response rates, of 1,3-bis(chloro-ethyl)-1-nitrosourea (BCNU) plus temozolomide in adult patients with recurrent glioblastoma multiforme. The phase 2 dose and schedule for this trial was BCNU 150 mg/m2 i.v. followed in 2 h by temozolomide 550 mg/m2 as a single oral dose. Treatment was repeated every 6 weeks for up to 8 cycles unless tumor progression was documented. The primary end point was PFS at 6 months (PFS-6). Response was a secondary end point, measured by MR imaging, neurological status, and steroid requirements prior to each 6-week cycle. The median age of eligible patients was 53, and 89.5% had no prior chemotherapy. All patients were evaluable for toxicity and time to progression. The PFS-6 was 21%. Overall survival was 68% at 6 months and 26% at 1 year. The MRI response for 36 patients was 2 partial responses, 2 minor responses, 19 cases of stable disease, and 13 immediate progressions. Median survival was 34 weeks, and median PFS was 11 weeks. Toxicity was primarily myelosuppression; no toxic deaths occurred. Historical phase 2 study data in this patient population show a PFS-6 of 15%. Recent data for use of temozolomide alone have shown a PFS-6 of 21%. We conclude that BCNU plus temozolomide when used in these doses and schedule has only modest activity, with significant toxicity, and appears to be no more effective than single-agent temozolomide.

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