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Phase II study of neoadjuvant 1, 3‐bis (2‐chloroethyl)‐1‐nitrosourea and temozolomide for newly diagnosed anaplastic glioma
Author(s) -
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
Publication year - 2004
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.20157
Subject(s) - medicine , temozolomide , nitrosourea , lomustine , anaplastic astrocytoma , glioma , carmustine , toxicity , oligodendroglioma , phases of clinical research , progressive disease , oncology , gastroenterology , surgery , chemotherapy , astrocytoma , cyclophosphamide , vincristine , cancer research
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/m 2 intravenously was followed after 2 hours by TMZ given at a dose of 550 mg/m 2 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.