Cytosine arabinoside in the management of recurrent leukaemia

A Phase II study of high dose cytosine arabinoside (ara-C) with different schedules in patients with recurrent acute myelogenous leukaemia (AML) and myeloid blast crisis of chronic myeloid leukaemia has been conducted at St. Bartholomew's Hospital. Ara-C was infused continuously for seven days at a dose of 100-200 mgs/m2 daily from day 1 with 1-2 g/m2 (3 h infusions) twice daily from day 2 for six days. Nineteen patients with acute myelogenous leukaemia and four patients with myeloid blast crisis of chronic myeloid leukaemia (CML) were treated. Complete remission was achieved in 4/19 patients with AML and in a further four patients an antileukaemic effect was observed. There were eight early deaths and three patients failed to show any response to therapy. All four patients with myeloid blast crisis of CML failed to respond to the treatment. Toxicity was considerable with gastro-intestinal and hepatotoxicity being the most serious problems. Pharmacokinetic studies revealed that mean basal levels achieved with continuous infusion prior to high-dose ara-C were 10(2) ng/ml and peak levels were of the order of 10(4) ng/ml. The considerable toxicity of the regimen, without clinical advantage over less intensive programmes, resulted in its termination.