title: Experimental chemotherapy of human medulloblastoma cell lines and transplantable xenografts with bifunctional alkylating agents.
abstract: A series of bifunctional alkylators were tested against the genotypically and phenotypically heterogeneous continuous human medulloblastoma cell lines, TE-671, Daoy, and D283 Med in vitro and against TE-671 and Daoy growing as s.c. and intracranial xenografts in athymic mice. Drugs tested included melphalan, cyclophosphamide, iphosphamide, phenylketocyclophosphamide, thiotepa, 1,3-bis(2-chloroethyl)-1-nitrosourea (in vivo), and busulfan (in vivo). Melphalan and phenylketocyclophosphamide were the most active agents in vitro with drug doses at which there is a 90% reduction in the number of colonies in comparison to controls of 2.13, 5.29, and 4.72 microM for melphalan and 4.60, 5.01, and 4.34 microM for phenylketocyclophosphamide against TE-671, D283 Med, and Daoy, respectively. Melphalan, cyclophosphamide, iphosphamide, phenylketocyclophosphamide, and thiotepa produced significant growth delays against s.c. TE-671 and Daoy xenografts, while no activity could be demonstrated for 1,3-bis(2-chloroethyl)-1-nitrosourea or busulfan. Melphalan, cyclophosphamide, iphosphamide, and thiotepa also produced significant increases in median survival in mice bearing intracranial TE-671 and Daoy xenografts. These results extend our previous studies demonstrating the antitumor activity of nitrogen and phosphoramide mustard-based bifunctional alkylating agents in the treatment of human medulloblastoma continuous cell lines and transplantable xenografts, and support the continued use of these agents in clinical trials.
authors.affiliation: Department of Pediatrics, Duke University Medical Center, Durham, North Carolina 27710.
authors.forename: H S
authors.initials: HS
authors.lastname: Friedman
authors.forename: O M
authors.initials: OM
authors.lastname: Colvin
authors.forename: S X
authors.initials: SX
authors.lastname: Skapek
authors.forename: S M
authors.initials: SM
authors.lastname: Ludeman
authors.forename: G B
authors.initials: GB
authors.lastname: Elion
authors.forename: S C
authors.initials: SC
authors.lastname: Schold
authors.forename: P F
authors.initials: PF
authors.lastname: Jacobsen
authors.forename: L H
authors.initials: LH
authors.lastname: Muhlbaier
authors.forename: D D
authors.initials: DD
authors.lastname: Bigner
mesh_terms: D000477:Alkylating Agents / Q000627:therapeutic use*; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy*; D002460:Cell Line; D003432:Cross-Linking Reagents; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D008527:Medulloblastoma / Q000188:drug therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation
chemical_list: D000477:Alkylating Agents; D000970:Antineoplastic Agents; D003432:Cross-Linking Reagents