Evaluation of cyclocytidine in reinduction and maintenance therapy of children with acute nonlymphocytic leukemia previously treated with cytosine arabinoside: a report from Children's Cancer Study Group.

A study of children in relapse with acute nonlymphocytic leukemia (ANLL) previously maintained in remission with combination chemotherapy including cytosine arabinoside (Ara-C) was undertaken by Children's Cancer Study Group (CCSG) to assess the efficacy of cyclocytidine (Cyclo-C), a depot Ara-C, compared to parenteral Ara-C given every 12 hr. The reinduction protocol consisted of daunomycin combined with either Ara-C (Regimen 1) or Cyclo-C (Regimen 2). One-hundred thirty eligible patients were entered on the randomized study. Hematologic toxicity was significant in both regimens and resulted in four drug-related deaths. Cardiac toxicity was observed in five patients, manifested only by abnormal echocardiogram or electrocardiogram patterns in three and congestive heart failure in two patients. Seventy-seven of 112 evaluable patients achieved M-1 or M-2A marrow remissions (69%): 46 of 60 on Regimen 1 (75%), 30 of 52 on Regimen 2 (60%). The remission rate between the two regimens was not significantly different. There was no significant difference in the duration of remission comparing maintenance cyclophosphamide combined with Ara-C or with Cyclo-C. Addition of VP-16 and CCNU to the maintenance therapy did not prolong the duration of remission. This study indicates that patients with childhood ANLL previously treated with Ara-C and daunomycin can obtain a successful second remission. A single daily subcutaneous dose of Cyclo-C was found to be as efficacious as Ara-C given intravenously every 12 hr. The single dose schedule provides a convenient way to treat patients with relapsed ANLL in the outpatient setting.