Phase II study of neoadjuvant 1, 3‐bis (2‐chloroethyl)‐1‐nitrosourea and temozolomide for newly diagnosed anaplastic glioma

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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. Cancer 2004. © 2004 American Cancer Society.