Phase II study of prolonged oral therapy with etoposide (VP16) for patients with recurrent malignant glioma

Abstract

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.