Because the percentage of dividing cells in
malignant gliomas is small, cell cycle specific drugs such as
VP16 are most effective if given continuously over prolonged periods. In this study, we chose a dose of 50 mg/day to minimize
therapy interruptions for myelosuppression.
VP16 was given until the neutrophil count dropped to < 1.0 x 10(9)/L or the platelets fell to < 75 x 10(9)/L and resumed when the counts rose to normal levels. We treated 46 patients with supratentorial
malignant glioma (15
anaplastic astrocytoma, 21
glioblastoma multiforme, 9
anaplastic oligodendroglioma, 1 undifferentiated primary malignant
brain tumor) at the time of
tumor progression. All had KPS > or = 70 at study entry. All patients had prior RT, 13 with adjuvant nitrosourea. Twenty-four had prior nitrosourea
chemotherapy for
tumor progression, 7 had no prior
chemotherapy. We treated 20 patients with
VP16 at first progression and 26 at second or later progression. All patients had CT or MR scans and clinical evaluation every 8 weeks. Median time to
tumor progression (
TTP) was 8.8 weeks for all evaluable patients, 8.6 weeks for those treated at first progression and 8.4 weeks for those treated at second progression, 9.1 weeks for
anaplastic astrocytoma, 7.5 weeks for
glioblastoma multiforme and 17.1 weeks for
anaplastic oligodendroglioma. There were 8 responses and 11 patients with stable disease for at least 8 weeks (R + SD = 42%). Prolonged low-dose oral VP15 is well tolerated, with minimal myelosuppression. Prolonged low-dose oral
VP16 is modestly effective treatment for patients with recurrent
malignant glioma and is more effective for
anaplastic astrocytoma and
anaplastic oligodendroglioma than
glioblastoma multiforme.