Chemotherapy and Radiation Therapy of Human Medulloblastoma in Athymic Nude Mice

Abstract

The human medulloblastoma cell line TE-671 was grown s.c. and intracranially in athymic nude mice. Tumor-bearing animals treated with chemotherapeutic agents or radiation were compared to untreated tumor-bearing controls. Tumors growing s.c. were sensitive to cyclophosphamide and vincristine with growth delays in duplicate trials of 15.8/16.5 and 12.9/15.0 days, respectively. These tumors were minimally responsive to the 2,5-bis(1-aziridinyl-3,6-dioxodiethyl ester of 1,4-cyclohexadiene-1.4-dicarbamic acid (NSC 182986) and cis-diamminedichloroplatinum II and unresponsive to methotrexate, 2,4-diamino-6-(2,5-dimethoxybenzyl)-5-methylpyrido(2,3-d)pyrimidine (NSC 351521), 1,3-bis(2-chloroethyl)-1-nitrosourea (NSC 409962), and procarbazine. Radiation therapy with 2500 or 1500 rads as a single fraction produced a marked response, with growth delays of 39.5 and 21.1 days, respectively. Cyclophosphamide produced a significant (p < 0.0005) increase in the median survival of mice with intracranial tumors. Vincristine produced a minimal increase in the median survival while no response was seen to the 2,5-bis(1-aziridinyl-3,6-dioxodiethylester of (1,4-cyclohexadiene-1,4-dicarbamic acid at the dose level and schedule tested. This model system will allow further analysis of the therapeutic sensitivity of human medulloblastoma to other agents or combinedmodality regimens.