Abstract
It has been shown in a variety of model systems that benznidazole (BENZO) is capable of enhancing the cytotoxicity of a number of drugs, including nitrosoureas. We report an escalating dose toxicity study of the combination of BENZO and CCNU on 34 patients in whom the usual clinical dose of CCNU (130 mg/m2) was given together with escalating doses of BENZO (up to a maximum dose of 40 mg/kg). We have observed no BENZO-related toxicity and no evidence that, in the dose range studied, BENZO enhances the gastrointestinal or hematological toxicity of CCNU. It is possible to administer the usual dose of CCNU together with doses of BENZO that can be shown to have a clear effect on the pharmacokinetics of CCNU and which might be expected, from the results of animal experiments, to produce enhancement of its cytotoxicity. A Phase III study of the combination is in progress.
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