Positive therapeutic interaction between thiopurines and alkylating drugs in human glioma xenografts.

Published

Journal Article

We used human anaplastic glioma xenografts to evaluate the therapeutic efficacy of combinations of alkylating drugs, either 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), 1-(2-chloroethyl)-3-(2,5-dioxo-3-piperidyl)-1-nitrosourea (PCNU), or procarbazine, and thiopurines, either 6-mercaptopurine (6MP) or 6-thioguanine (6TG). Using growth delay as the endpoint in subcutaneous (s.c.) tumors and increased life span as the endpoint in intracranial (i.c.) tumors, we found that combinations of chloroethylnitrosoureas (CENUs) and thiopurines were significantly more active than either type of agent alone. In contrast, combinations of procarbazine and thiopurines were not significantly more active than procarbazine alone. The therapeutic potentiation of the CENU was greater when the latter was given on the 4th day of the thiopurine treatment cycle than when it was given on the 1st day. Characterization of the interaction between CENUs and thiopurines also revealed a supraadditive therapeutic response at higher BCNU doses in combination with 6TG. Interaction between the nitrosoureas and the thiopurines probably occurs in the guanine base of tumor DNA and has important therapeutic implications.

Full Text

Duke Authors

Cited Authors

  • Wang, AM; Elion, GB; Friedman, HS; Bodell, WJ; Bigner, DD; Schold, SC

Published Date

  • 1991

Published In

Volume / Issue

  • 27 / 4

Start / End Page

  • 278 - 284

PubMed ID

  • 1998983

Pubmed Central ID

  • 1998983

International Standard Serial Number (ISSN)

  • 0344-5704

Digital Object Identifier (DOI)

  • 10.1007/bf00685112

Language

  • eng

Conference Location

  • Germany