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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 SM, Prados MD, Yung WK, Fine H, Junck L, Greenberg H, Robins HI, Mehta
M, Fink KL, Jaeckle KA, Kuhn J, Hess K, Schold C
Department of Neurological Surgery, Neuro-Oncology Service,
University of California at San Francisco, San Francisco, California 94143, USA.
changs@neurosurg.ucsf.edu.
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) > or = 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.
Copyright 2004 American Cancer Society.
PMID: 15073861 [PubMed - indexed for MEDLINE]
Source: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15073861
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