Tauromustine (
TCNU), 130 mg/sq m, was administered intraoperatively by nasogastric tube to 10 patients with
malignant glioma (seven
glioblastomas and three
anaplastic astrocytomas). High-performance liquid chromatography analysis of 32
tumor specimens for
TCNU revealed that tissue concentrations ranged from 0 to 554 ng/gm:
TCNU was not detected in necrotic regions of the
tumor. Levels of
TCNU in brain adjacent to
tumor were similar to those recorded within the
gliomas (range 0 to 635 ng/gm). The variability in the tissue level of
TCNU was partly attributable to variable absorption of the
drug, since peak plasma
TCNU levels ranged from 164 to 3333 ng/ml. There were close quantitative and temporal relationships between the times of peak plasma levels (median 456 ng/ml at 45 minutes after administration), peak
tumor levels (median 250 ng/gm tissue at 55 minutes), and brain adjacent to
tumor levels (median 256 ng/gm tissue at 50 minutes). Linear regression analysis of the ratio between tissue and plasma
TCNU levels at particular times after
drug administration suggest that plasma concentrations can be used to estimate tissue concentrations. This study demonstrates that
TCNU enters
malignant glioma. In view of the activity of
TCNU against a range of
tumors, a full clinical evaluation of this new nitrosourea in
malignant glioma seems justified.