The role of idarubicin in adult acute lymphoblastic leukaemia: From drug resistance studies to clinical application

Idarubicin (4-demethoxydaunorubicin) is more potent and less cardiotoxic than daunorubicin or doxorubicin. These properties suggested a role in acute myelogenous leukaemia, that was confirmed by prospective randomized trials. In acute lymphoblastic leukaemia of adults, on the contrary, there is very little information regarding idarubicin. We have used idarubicin since 1991 and found, in a retrospective comparison with a doxorubicin regimen, a decreased incidence of primarily refractory disease. The role of idarubicin in the postremission phase could not be assessed in detail but an early intensive use of anthracyclines, either idarubicin or doxorubicin, was associated with an improved outcome in early-B CD10⁺ and t(9;22)/BCR leukaemias. Concurrent in vitro studies demonstrated that idarubicin, at pharmacologically relevant concentrations, was less sensitive to P-glycoprotein-mediated drug efflux than daunorubicin and was a more effective agent to use with cyclosporin-A to circumvent this drug resistance mechanism. Idarubicin is a very effective drug for the early management of adult acute lymphoblastic leukaemia and may be presently considered (along with cyclosporin-A or other modulator) as the reference anthracycline for cases overexpressing the P-glycoprotein drug resistance mechanism.