Schedule-dependent synergism for the combination of 1-beta-D-arabinofuranosylcytosine and daunorubicin.

Abstract

Summary Studies utilizing the spleen colony assay for both leukemic and normal hematopoietic colony-forming units indicate that the effectiveness of the combination of 1-β-d-arabinofuranosylcytosine (ara-C) and daunorubicin (Daun) in killing leukemic cells is highly schedule dependent. When the two agents are given simultaneously, the degree of cell kill is less than additive; that is, the level of survival is greater than that given by the product of the leukemic colony-forming unit survival for the two agents used separately. When Daun is given before ara-C, the resulting cell kill is additive. However, if, Daun is given from 2 to 40 hr after ara-C, a marked increase in cell kill occurs reaching a maximum when the two agents are given 15 hr apart. The survival of normal colony-forming units utilizing the same doses in combination is never less than that defined as additive. Studies using different doses of ara-C and Daun with an optimum time interval between drug administration indicate that the synergism observed for the leukemic colony forming units is dependent upon the doses of both agents.