A comparison of in vitro sensitivity of acute myeloid leukemia precursors to mitoxantrone, 4'deoxydoxorubicin, 4-demethoxydaunorubicin and daunorubicin

Abstract

The development of new chemotherapeutic drugs for the treatment of AML remains of continuous interest. Three new drugs currently under investigation in phase II and III clinical trials, i.e. Mitoxantrone, 4'deoxydoxorubicin and 4-demethoxydaunorubicin, were studied in vitro to directly compare their relative cytotoxicity on AML clonogenic cells from six patients. The data were compared to the sensitivity of normal bone marrow myeloid and erythroid clonogenic cells and to results obtained in similar experiments for daunorubicin. A dose dependent cytoreduction of AML and normal bone marrow progenitors was found in all cases after preincubation with the drugs. The relative cytoreductive efficacies of the different agents always correlated when tested upon the cells from the same patient. Cross resistance was demonstrated in a case of daunorubicin refractory AML. Normal bone marrow myeloid and erythroid progenitors were significantly more sensitive to the drugs than AML clonogenic cells. These in vitro data suggest that none of the new drugs is superior to daunorubicin, when the quantitative degree of cytotoxicity to AML clonogenic cells, or normal bone marrow progenitors are taken into account.