BUSULFAN THERAPY OF CENTRAL-NERVOUS-SYSTEM XENOGRAFTS IN ATHYMIC MICE

We evaluated the antitumor activity of busulfan against a panel of tum or cell lines and xenografts in athymic nude mice derived from childho od high-grade glioma, adult high-grade glioma, ependymoma, and medullo blastoma. Busulfan displayed similar activity against a panel of four medulloblastoma cell Lines (D283 Med, Daoy, D341 Med, and D425 Med) an d four corresponding sublines with laboratory-generated or clinically acquired resistance to 4-hydroperoxycyclophosphamide [D283 Med (4-HCR) , Daoy (4-HCR), D341 Med (4-HCR), and D458 Med] and cross-resistance t o melphalan. This is consistent with a nearly total lack of cross-resi stance of busulfan to 4-hydroperoxycyclophosphamide. Busulfan was acti ve in the therapy of all but one of the subcutaneous xenografts tested , with growth delays ranging from 14.3 days in D612 EP to 58.4 days in D528 EP. Busulfan produced statistically Significant increases in the median survival of mice bearing intracranial D456 MG (66%-90%), D612 EP (18%-33%), and D528 EP (89%) xenografts. These studies suggest that busulfan may be active against medulloblastomas, high-grade gliomas, and ependymomas as well as against cyclophosphamide-resistant neoplasm s.