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 A. 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

Fingerprint

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

Keywords

  • 1, 3-bis (2-chloroethyl)-1-nitrosourea (BCNU)
  • Anaplastic glioma
  • Neoadjuvant strategy
  • Temozolomide

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

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 A.; Kuhn, John; Hess, Kenneth; Schold, Clifford.

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

Research output: Contribution to journalArticle

Chang, SM, Prados, MD, Yung, WKA, Fine, H, Junck, L, Greenberg, H, Robins, HI, Mehta, M, Fink, KL, Jaeckle, KA, 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
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 A. ; 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.
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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.",
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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 A.

AU - Kuhn, John

AU - Hess, Kenneth

AU - Schold, Clifford

PY - 2004/4/15

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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.

KW - 1, 3-bis (2-chloroethyl)-1-nitrosourea (BCNU)

KW - Anaplastic glioma

KW - Neoadjuvant strategy

KW - Temozolomide

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