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
✍ Scribed by 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
- Publisher
- John Wiley and Sons
- Year
- 2004
- Tongue
- English
- Weight
- 77 KB
- Volume
- 100
- Category
- Article
- ISSN
- 0008-543X
No coin nor oath required. For personal study only.
✦ Synopsis
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/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.