title: The use of intermediate dose cytosine arabinoside (ID Ara-C) in the treatment of acute non-lymphocytic leukaemia in relapse.
abstract: 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.
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003561:Cytarabine / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D004317:Doxorubicin / Q000008:administration & dosage; D006207:Half-Life; D006801:Humans; D007938:Leukemia / Q000188:drug therapy*; D008875:Middle Aged; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D003561:Cytarabine; D014750:Vincristine; D004317:Doxorubicin