Ongoing phase I and II studies of novel anthracyclines.

Many anthracyclines are currently in clinical development with the common aim of improving selectivity. This could be achieved by improving tumor drug delivery through the identification and development of molecules with new structure, prodrugs with low molecular weight for selective release and activation, prodrugs with high molecular weight conjugated to antibody with active targeting or macromolecules with enhanced permeability and retention. There are still interfering factors to be defined, in particular chemical, with degradation steps in tumor tissues, biological, related to tumor proteases, pharmacological, with inter-individual tumor differences in the extent of accumulation. Another way to improve selectivity is to activate the drug at the tumor site, a good example of which is provided by Nemorubicin (2"-(S)-methoxymorpholinodoxorubicin hydrochloride) in hepatocellular carcinoma. The favorable characteristics of Nemorubicin in terms of broad spectrum of significant antitumor activity in liver malignancies models, lower cardiotoxicity than Doxorubicin, make Nemorubicin a promising third-generation anthracycline, suitable for intrahepatic administration.