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High dose cytarabine: a review
B J Bolwell1, P A Cassileth, R P Gale
1Hematology-Oncology Section, University of Pennsylvania School of Medicine, Philadelphia.
High dose cytarabine (HDARAC) therapy is used increasingly to treat hematologic malignancies. Recent data indicate that HDARAC at doses of 2-3 g/M2 every 12 hr x 10-12 doses is of comparable or greater efficacy in remission induction as standard doses of cytarabine in acute myelogenous leukemia. HDARAC can also produce remissions in individuals resistant to conventional doses. HDARAC-containing regimens are reported to result in substantially higher long-term, disease-free survival than previous approaches to post-remission therapy, but this has not yet been confirmed in controlled trials. HDARAC is also active in acute lymphocytic leukemia. Because intravenous HDARAC achieves high levels in the spinal fluid, it is useful to treat central nervous system leukemia and may provide adequate CNS prophylaxis in acute lymphocytic leukemia. HDARAC is reported to be active in advanced non-Hodgkin lymphomas and chronic myelogenous leukemia in acute phase; optimal use in these settings is under study. HDARAC has also been combined with other drugs. Randomized trials are needed to determine whether these combinations are more effective than HDARAC alone. Apart from potent myelosuppression, the dose-limiting toxicity of HDARAC is cerebellar damage. This occurs with increased frequency in patients greater than 50 years old. HDARAC is active in hematologic malignancies and may further improve therapeutic results if combined with other drugs.
High dose cytarabine (HDARAC) therapy is used increasingly to treat hematologic malignancies. Recent data indicate that HDARAC at doses of 2-3 g/M2 every 12 hr x 10-12 doses is of comparable or greater efficacy in remission induction as standard doses of cytarabine in acute myelogenous leukemia. HDARAC can also produce remissions in individuals resistant to conventional doses. HDARAC-containing regimens are reported to result in substantially higher long-term, disease-free survival than previous approaches to post-remission therapy, but this has not yet been confirmed in controlled trials. HDARAC is also active in acute lymphocytic leukemia. Because intravenous HDARAC achieves high levels in the spinal fluid, it is useful to treat central nervous system leukemia and may provide adequate CNS prophylaxis in acute lymphocytic leukemia. HDARAC is reported to be active in advanced non-Hodgkin lymphomas and chronic myelogenous leukemia in acute phase; optimal use in these settings is under study. HDARAC has also been combined with other drugs. Randomized trials are needed to determine whether these combinations are more effective than HDARAC alone. Apart from potent myelosuppression, the dose-limiting toxicity of HDARAC is cerebellar damage. This occurs with increased frequency in patients greater than 50 years old. HDARAC is active in hematologic malignancies and may further improve therapeutic results if combined with other drugs.
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