Experimental chemotherapy of human medulloblastoma with classical alkylators

Seven classical alkylators were tested for activity against the continuous human medulloblastoma cell line TE-671 grown in vitro and as s.c. and intracranial xenografts in athymic mice. Drugs tested included melphalan, cyclophosphamide (4-hydroperoxycyclophosphamide in vitro), iphosphamide (4-hydrop...

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Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 1986-06, Vol.46 (6), p.2827-2833
Main Authors: FRIEDMAN, H. S, COLVIN, O. M, LUDEMAN, S. M, SCHOLD, S. C. JR, BOYD, V. L, MULHBAIER, L. H, BIGNER, D. D
Format: Article
Language:English
Subjects:
Alkylating Agents - metabolism
Alkylating Agents - therapeutic use
Alkylating Agents - toxicity
Animals
Antineoplastic agents
Biological and medical sciences
Blood Cells - drug effects
Brain Neoplasms - drug therapy
Cell Line
Chemotherapy
Cyclophosphamide - therapeutic use
Female
Humans
Male
Medical sciences
Medulloblastoma - drug therapy
Melphalan - therapeutic use
Mice
Mice, Inbred BALB C
Neoplasm Transplantation
Pharmacology. Drug treatments
Skin Neoplasms - drug therapy
Transplantation, Heterologous
Tumor Stem Cell Assay
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Summary:Seven classical alkylators were tested for activity against the continuous human medulloblastoma cell line TE-671 grown in vitro and as s.c. and intracranial xenografts in athymic mice. Drugs tested included melphalan, cyclophosphamide (4-hydroperoxycyclophosphamide in vitro), iphosphamide (4-hydroperoxyiphosphamide in vitro), phenylketocyclo-phosphamide, phenylketoiphosphamide, Asta Z 7557, and thiotriethyl-enephosphoramide. All agents were active, with melphalan demonstrating the most activity in vitro and in vivo. Comparative studies of cyclophosphamide and phenylketocyclophosphamide revealed partition coefficients (log P) of 0.73 and greater than 1.69, respectively, and cyclophosphamide exhibited greater cytotoxic activity in post- (equitoxic) drug administration murine plasma. Hematological toxicity was limited to leukopenia/neutropenia for both of these agents. These studies suggest that the classical alkylators may have a role in the treatment of medulloblastoma and provide a means to further analyze their therapeutic potential.
ISSN:0008-5472
1538-7445