Phase II Study of Neoadjuvant 1, 3-Bis (2-Chloroethyl)-1-Nitrosourea and Temozolomide for Newly Diagnosed Anaplastic Glioma: A North American Brain Tumor Consortium Trial

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

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

BACKGROUND. Temozolomide (TMZ) and 1, 3-bis (2-chloroethyl)-1-nitrosourea (BCNU) are reported to be active agents in anaplastic glioma (AG). TMZ has also been shown to deplete alkyltransferase, a DNA repair enzyme that contributes to nitrosourea resistance. The objective of the current study was to determine the efficacy and toxicity profile of a combination of these agents before radiotherapy in newly diagnosed AG. METHODS. Eligibility criteria included histologically confirmed newly diagnosed AG with measurable enhancing disease, a Karnofsky performance score (KPS) ≥ 60, normal pulmonary function, and normal laboratory parameters. In addition, informed consent was obtained from all patients. BCNU given at a dose of 150 mg/m2 intravenously was followed after 2 hours by TMZ given at a dose of 550 mg/m2 orally on Day 1 of a 42-day cycle to a maximum of 4 cycles, unless there was tumor progression or unacceptable toxicity. RESULTS. Forty-one eligible patients were accrued. Their median age was 40 years. Seventy-six percent of patients had a KPS of 90-100. The histology was 81% anaplastic astrocytoma, 12% anaplastic oligodendroglioma, and 7% mixed tumors. Twenty-two percent of patients did not complete 4 cycles because of toxicity, mainly hematologic. Forty-six percent of patients experienced Grade 3 or 4 (according to National Cancer Institute Common Toxicity Criteria) thrombocytopenia. Twenty percent had Grade 4 granulocytopenia. Two patients died while receiving therapy, 1 of progressive disease and the other of Pneumocystis carinii pneumonia. The complete and partial response rates were 2% and 27% respectively. An additional 54% of patients had stable disease. Seventeen percent developed progressive disease (10% after the first cycle and 7% after the second cycle). CONCLUSIONS. This neoadjuvant strategy was associated with significant myelosuppression and a modest response rate in patients with newly diagnosed AG.

Original languageEnglish (US)
Pages (from-to)1712-1716
Number of pages5
JournalCancer
Volume100
Issue number8
DOIs
StatePublished - Apr 15 2004

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temozolomide
Carmustine
Brain Neoplasms
Glioma
Alkyl and Aryl Transferases
DNA Repair Enzymes
Oligodendroglioma
Agranulocytosis
Pneumocystis Pneumonia
National Cancer Institute (U.S.)
Astrocytoma
Informed Consent
Thrombocytopenia

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Chang, Susan M. ; Prados, Michael D. ; Yung, W. K.Alfred ; Fine, Howard ; Junck, Larry ; Greenberg, Harry ; Robins, H. Ian ; Mehta, Minesh ; Fink, Karen L. ; Jaeckle, Kurt ; Kuhn, John ; Hess, Kenneth ; Schold, Clifford. / Phase II Study of Neoadjuvant 1, 3-Bis (2-Chloroethyl)-1-Nitrosourea and Temozolomide for Newly Diagnosed Anaplastic Glioma : A North American Brain Tumor Consortium Trial. In: Cancer. 2004 ; Vol. 100, No. 8. pp. 1712-1716.
@article{a5764ecf298c4676ac1e176d094ebb14,
title = "Phase II Study of Neoadjuvant 1, 3-Bis (2-Chloroethyl)-1-Nitrosourea and Temozolomide for Newly Diagnosed Anaplastic Glioma: A North American Brain Tumor Consortium Trial",
abstract = "BACKGROUND. Temozolomide (TMZ) and 1, 3-bis (2-chloroethyl)-1-nitrosourea (BCNU) are reported to be active agents in anaplastic glioma (AG). TMZ has also been shown to deplete alkyltransferase, a DNA repair enzyme that contributes to nitrosourea resistance. The objective of the current study was to determine the efficacy and toxicity profile of a combination of these agents before radiotherapy in newly diagnosed AG. METHODS. Eligibility criteria included histologically confirmed newly diagnosed AG with measurable enhancing disease, a Karnofsky performance score (KPS) ≥ 60, normal pulmonary function, and normal laboratory parameters. In addition, informed consent was obtained from all patients. BCNU given at a dose of 150 mg/m2 intravenously was followed after 2 hours by TMZ given at a dose of 550 mg/m2 orally on Day 1 of a 42-day cycle to a maximum of 4 cycles, unless there was tumor progression or unacceptable toxicity. RESULTS. Forty-one eligible patients were accrued. Their median age was 40 years. Seventy-six percent of patients had a KPS of 90-100. The histology was 81{\%} anaplastic astrocytoma, 12{\%} anaplastic oligodendroglioma, and 7{\%} mixed tumors. Twenty-two percent of patients did not complete 4 cycles because of toxicity, mainly hematologic. Forty-six percent of patients experienced Grade 3 or 4 (according to National Cancer Institute Common Toxicity Criteria) thrombocytopenia. Twenty percent had Grade 4 granulocytopenia. Two patients died while receiving therapy, 1 of progressive disease and the other of Pneumocystis carinii pneumonia. The complete and partial response rates were 2{\%} and 27{\%} respectively. An additional 54{\%} of patients had stable disease. Seventeen percent developed progressive disease (10{\%} after the first cycle and 7{\%} after the second cycle). CONCLUSIONS. This neoadjuvant strategy was associated with significant myelosuppression and a modest response rate in patients with newly diagnosed AG.",
author = "Chang, {Susan M.} and Prados, {Michael D.} and Yung, {W. K.Alfred} and Howard Fine and Larry Junck and Harry Greenberg and Robins, {H. Ian} and Minesh Mehta and Fink, {Karen L.} and Kurt Jaeckle and John Kuhn and Kenneth Hess and Clifford Schold",
year = "2004",
month = "4",
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doi = "10.1002/cncr.20157",
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Chang, SM, Prados, MD, Yung, WKA, Fine, H, Junck, L, Greenberg, H, Robins, HI, Mehta, M, Fink, KL, Jaeckle, K, Kuhn, J, Hess, K & Schold, C 2004, 'Phase II Study of Neoadjuvant 1, 3-Bis (2-Chloroethyl)-1-Nitrosourea and Temozolomide for Newly Diagnosed Anaplastic Glioma: A North American Brain Tumor Consortium Trial', Cancer, vol. 100, no. 8, pp. 1712-1716. https://doi.org/10.1002/cncr.20157

Phase II Study of Neoadjuvant 1, 3-Bis (2-Chloroethyl)-1-Nitrosourea and Temozolomide for Newly Diagnosed Anaplastic Glioma : A North American Brain Tumor Consortium Trial. / Chang, Susan M.; Prados, Michael D.; Yung, W. K.Alfred; Fine, Howard; Junck, Larry; Greenberg, Harry; Robins, H. Ian; Mehta, Minesh; Fink, Karen L.; Jaeckle, Kurt; Kuhn, John; Hess, Kenneth; Schold, Clifford.

In: Cancer, Vol. 100, No. 8, 15.04.2004, p. 1712-1716.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Phase II Study of Neoadjuvant 1, 3-Bis (2-Chloroethyl)-1-Nitrosourea and Temozolomide for Newly Diagnosed Anaplastic Glioma

T2 - A North American Brain Tumor Consortium Trial

AU - Chang, Susan M.

AU - Prados, Michael D.

AU - Yung, W. K.Alfred

AU - Fine, Howard

AU - Junck, Larry

AU - Greenberg, Harry

AU - Robins, H. Ian

AU - Mehta, Minesh

AU - Fink, Karen L.

AU - Jaeckle, Kurt

AU - Kuhn, John

AU - Hess, Kenneth

AU - Schold, Clifford

PY - 2004/4/15

Y1 - 2004/4/15

N2 - BACKGROUND. Temozolomide (TMZ) and 1, 3-bis (2-chloroethyl)-1-nitrosourea (BCNU) are reported to be active agents in anaplastic glioma (AG). TMZ has also been shown to deplete alkyltransferase, a DNA repair enzyme that contributes to nitrosourea resistance. The objective of the current study was to determine the efficacy and toxicity profile of a combination of these agents before radiotherapy in newly diagnosed AG. METHODS. Eligibility criteria included histologically confirmed newly diagnosed AG with measurable enhancing disease, a Karnofsky performance score (KPS) ≥ 60, normal pulmonary function, and normal laboratory parameters. In addition, informed consent was obtained from all patients. BCNU given at a dose of 150 mg/m2 intravenously was followed after 2 hours by TMZ given at a dose of 550 mg/m2 orally on Day 1 of a 42-day cycle to a maximum of 4 cycles, unless there was tumor progression or unacceptable toxicity. RESULTS. Forty-one eligible patients were accrued. Their median age was 40 years. Seventy-six percent of patients had a KPS of 90-100. The histology was 81% anaplastic astrocytoma, 12% anaplastic oligodendroglioma, and 7% mixed tumors. Twenty-two percent of patients did not complete 4 cycles because of toxicity, mainly hematologic. Forty-six percent of patients experienced Grade 3 or 4 (according to National Cancer Institute Common Toxicity Criteria) thrombocytopenia. Twenty percent had Grade 4 granulocytopenia. Two patients died while receiving therapy, 1 of progressive disease and the other of Pneumocystis carinii pneumonia. The complete and partial response rates were 2% and 27% respectively. An additional 54% of patients had stable disease. Seventeen percent developed progressive disease (10% after the first cycle and 7% after the second cycle). CONCLUSIONS. This neoadjuvant strategy was associated with significant myelosuppression and a modest response rate in patients with newly diagnosed AG.

AB - BACKGROUND. Temozolomide (TMZ) and 1, 3-bis (2-chloroethyl)-1-nitrosourea (BCNU) are reported to be active agents in anaplastic glioma (AG). TMZ has also been shown to deplete alkyltransferase, a DNA repair enzyme that contributes to nitrosourea resistance. The objective of the current study was to determine the efficacy and toxicity profile of a combination of these agents before radiotherapy in newly diagnosed AG. METHODS. Eligibility criteria included histologically confirmed newly diagnosed AG with measurable enhancing disease, a Karnofsky performance score (KPS) ≥ 60, normal pulmonary function, and normal laboratory parameters. In addition, informed consent was obtained from all patients. BCNU given at a dose of 150 mg/m2 intravenously was followed after 2 hours by TMZ given at a dose of 550 mg/m2 orally on Day 1 of a 42-day cycle to a maximum of 4 cycles, unless there was tumor progression or unacceptable toxicity. RESULTS. Forty-one eligible patients were accrued. Their median age was 40 years. Seventy-six percent of patients had a KPS of 90-100. The histology was 81% anaplastic astrocytoma, 12% anaplastic oligodendroglioma, and 7% mixed tumors. Twenty-two percent of patients did not complete 4 cycles because of toxicity, mainly hematologic. Forty-six percent of patients experienced Grade 3 or 4 (according to National Cancer Institute Common Toxicity Criteria) thrombocytopenia. Twenty percent had Grade 4 granulocytopenia. Two patients died while receiving therapy, 1 of progressive disease and the other of Pneumocystis carinii pneumonia. The complete and partial response rates were 2% and 27% respectively. An additional 54% of patients had stable disease. Seventeen percent developed progressive disease (10% after the first cycle and 7% after the second cycle). CONCLUSIONS. This neoadjuvant strategy was associated with significant myelosuppression and a modest response rate in patients with newly diagnosed AG.

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DO - 10.1002/cncr.20157

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