Section Review Oncologic,Endocrine & Metabolic: Recent developments with novel anthracyclines for the treatment of haematological malignancies

This review discusses recent developments with novel anthracyclines for the treatment of haematological malignancies. The acquisition of the active 13-hydroxy (-OH) derivatives of anthracyclines is fascinating, as their derivatives are persistent in blood, whilst those of daunorubicin and doxorubicin are inactive. Chemical modification of daunorubicin led to the newly developed anthracycline, idarubicin, whose 13-OH derivative, idarubicinol, is active in vivo. Idarubicin is superior to daunorubicin in the treatment of acute myelogenous leukaemia. Amrubicin (SM-5887), another newly synthesised anthracycline, has a unique structure with an amino residue introduced at the C-9 position. The most characteristic feature is that amrubicin itself is a depot form of its active 13-OH derivative. Amrubicin is less cardiotoxic than doxorubicin in the chronic rabbit model. This may be due, in part, to the fact that cardiotoxicity depends on the C_max of the drug, since the 13-OH derivative maintains a relatively low plasma level persistently. Amrubicin is expected to be effective against non-Hodgkin's lymphoma. In addition, the development of orally active drugs, predominantly to allow out-patient treatment of lymphoma and myeloma, is described. Menogaril, an analogue of nogalamycin, is one such novel anthracycline. It can be administered orally and its bioavailability is estimated to be 32 ± 12%. Although the clinical outcome following iv. administration was disappointing, oral treatment with menogaril is expected to be useful for patients with lymphoma and breast cancer. Further studies are required to clarify the effectiveness of these drugs.