Potentiation of the antitumor therapeutic effects of 1,3-bis(2-chloroethyl)-1-nitrosourea by alpha-difluoromethylornithine, an ornithine decarboxylase inhibitor.

alpha-Difluoromethylornithine (DFMO), an enzyme-activated irreversible inhibitor of ornithine decarboxylase, was used alone and in combination with various single doses of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) to treat animals bearing murine glioma 26 and rat 9L gliosarcoma intracerebral tumors. Used as a single agent, DFMO has little or no effect against these tumors. However, in both intracerebral tumor models, pretreatment with DFMO p.o. before i.p. administration of BCNU potentiates the effect of BCNU without increasing toxicity. The effects of DFMO administered p.o. after BCNU or before and after various doses of BCNU indicate that DFMO may also effectively slow the repopulation of these tumors after BCNU therapy.