The use of intermediate dose cytosine arabinoside (ID Ara-C) in the treatment of acute non-lymphocytic leukaemia in relapse.

Cytosine arabinoside in a high dose of 3 g/m2 (HD Ara-C), alone or in combination with doxorubicin, has been advocated for the treatment of patients with acute non-lymphocytic leukaemia (ANLL) in relapse. Although a remission rate of 65% has been reported, the toxicity was severe and was possibly related to the high plasma concentrations of Ara-C (about 100 microM) reached during 1 h infusion. It has been postulated, however, that the intracellular enzymes which convert Ara-C into the active metabolite cytosine arabinoside triphosphate (Ara-CTP), are saturated at plasma concentrations of about 10 microM. We calculated that this level could be reached with an intermediate dose of 0.5 g/m2 Ara-C, given in a 1 h infusion (ID Ara-C). Subsequently 15 patients with ANLL (12 in relapse and three refractory to conventional therapy) were treated with ID Ara-C every 12 h for 6 d in combination with doxorubicin and vincristine. The overall remission rate was 80%. The median duration of bone marrow depression was 20 d (range 14-29 d) and side effects were comparable to conventional treatment. These preliminary data suggest that the therapeutic results of this ID Ara-C regimen are not inferior to comparable schedules with HD Ara-C as reported by others while toxicity is less severe.