In vivo efficacy and tumor-selective metabolism of amrubicin to its activemetabolite

The tissue distribution of a novel antitumor anthracycline antibiotic, amru bicin, was studied using seven human tumor xenografts implanted into nude m ice, in order to identify the principal factors determining its therapeutic efficacy. We found a good correlation between the level of the metabolite amrubicinol in the tumor and the in vivo efficacy High metabolic activity o f amrubicin to amrubicinol was detected in tumor tissue homogenates, especi ally in cell lines highly sensitive to amrubicin in vivo. In contrast to am rubicin, the administration of amrubicinol showed less tumor-selective toxi city in these human tumor xenograft models. These data indicate that the tu mor-selective metabolism of amrubicin to amrubicinol resulted in a tumor-se lective disposition of amrubicinol, leading to good efficacy in in vivo exp erimental therapeutic models.