Intermediate-Dose Cytarabine in the Treatment of Relapsed or Refractory Leukemias
High-dose cytarabine (HD ARA-C) has been extensively used in relapsed acute myeloid leukemia (AML), either alone  or in combination with asparaginase , daunorubicin (DNR) , amsacrine (AMSA) , or mitoxantrone . With this high-dose regimen (3 g/m2 twice daily for 4–6 days), high remission reinduction rates have been achieved, but at the expense of significant toxicity, in particular cerebellar toxicity . This complication, which may be irreversible and/or fatal, is dose related and precludes total doses over 48 g/m2 per cycle. It is mainly encountered for total doses of 36 g/m2 (3 g/m2 for 12 doses) or more. The incidence of severe cerebellar toxicity is also related to age, patients >50 years of age having a greater incidence than younger patients . In order to reduce the major toxicities of HD ARA-C, some investigators have used combinations of AMSA or mitoxantrone (MTZ) at optimal dosage with ARA-C at lower cumulative doses [7, 8]. Van Prooijen et al. treated 15 relapsed AML patients with cytarabine (500 mg/m2 every 12 h for 6 days) in combination with doxorubicin and vincristine and obtained 80% CR . Moreover, infusions of ARA-C at doses lower than the standard dose of 3 g/m2 maintain plasma ARA-C levels sufficient to saturate the cellular ARA-CTP accumulation . Thus, cytarabine could be used at intermediate-dose (ID ARA-C) with the same efficacy but less toxicity than in HD ARA-C containing regimens.
KeywordsToxicity Leukemia Diarrhea Doxorubicin Prednisone
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