Polyamine deprivation enhances antitumoral efficacy of chemotherapy

Abstract

We reported previously that polyamine deprivation by feeding a polyamine deficient diet combined with gastrointestinal tract decontamination and polyamine oxidase inhibition considerably enhanced the antitumoral effect of DFMO, a selective inhibitor of ornithine decarboxylase. The combination of polyamine deprivation and administration of well established cytotoxic drugs was expected to improve further the antitumoral effect of polyamine deprivation in Lewis lung carcinoma grafted in mice. Simultaneous treatment, i.e. administration of the cytotoxic drugs during the polyamine deprivation regimen, reduced tumor growth, but enhanced toxic effects. By alternating treatment and polyamine deprivation (1st day methotrexate (1.7 mg/kg), 2nd day cyclophosphamide (90 mg/kg), 3rd day vindesine (0.25 mg/kg), followed by five days of polyamine deprivation), tumor growth was reduced by 90% and an increase of 64% in the survival time of the animals was observed, demonstrating that a significant enhancement of the efficacy of chemotherapy was achieved without concomitant enhancement of toxic effects.