High-dose cytosine arabinoside in the treatment of acute myeloid leukaemia.
Cytosine arabinoside (Ara-C) has earned its recognition as the most important antileukaemic drug currently available for the treatment of acute myeloid leukaemia. Approximately 60-80% of patients less than 60 years of age can be expected to enter complete remission if treated with standard-dose Ara-C (100-200 mg/m2) in combination with an anthracycline. The efficacy of Ara-C appears clinically to be dose and schedule dependent. A 15-30 fold dose escalation in Ara-C can elicit a therapeutic response in patients who have previously failed treatment with standard-dose Ara-C or other anti-leukaemic drugs. The use of high-dose cytosine arabinoside (HDAC 3 gm/m2) appears rational based on cytosine pharmacology. Drug-scheduling is used to exploit drug synergy when HDAC is given in combination with asparaginase or fludarabine (+/- G-CSF) in a schedule-dependent fashion. Toxicity following Ara-C is also dose- and schedule-dependent. Central nervous system toxicity--particularly cerebellar dysfunction--although rare, is particularly serious because it may preclude further use of the drug. Older patients are particularly susceptible. This article will describe the rationale for and the value of HDAC alone or in combination with other cytotoxics in the treatment of acute myeloid leukaemia.
Cole
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N
Department of Haematology, Royal Hospital for Sick Children, Glasgow, UK.
Gibson
B E
BE
D000208:Acute Disease; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage*; D003561:Cytarabine / Q000008:administration & dosage*; D006801:Humans; D007951:Leukemia, Myeloid / Q000188:drug therapy*
D000964:Antimetabolites, Antineoplastic; D003561:Cytarabine