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

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42 Scopus citations


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
Issue number8
StatePublished - Apr 15 2004


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

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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