Figure

Cytarabine is structurally similar to cytidine except for the sugar moiety (arabinose replaces ribose; see Fig. 2.9) [8,21]. After intracellular phos-phorylation to ara-C triphosphate, the drug is incorporated into DNA and inhibits DNA polymerase. In addition, cytarabine can slow the elongation of DNA and induce premature chain termination [144]. Cytarabine can be administered intravenously or intrathecally and does penetrate the blood-brain barrier. It is usually a component of methotrexate-based regimens for the treatment of primary central nervous system lymphoma [71-73,145,146]. DeAngelis and colleagues recommend using cytarabine as con-solidative therapy (3 g/m2 per dose IV for two days) after methotrexate or irradiation for two cycles. For patients with leptomeningeal metastasis from systemic malignancies or PBT, cytarabine (30 mg/m2 per dose) is often efficacious. Common toxicities include myelosuppression, nausea, emesis, and neurological dysfunction, such as cerebellar syndrome, encephalopathy, seizures, and myelopathy [144].

Purine analogs. This class consists of 6-mercap-topurine and 6-thioguanine, which have a thiol moiety substituted for a hydroxyl group on the purine ring [8,21]. Both the agents are orally administered and require activation by the enzyme hypox-anthineguanine phosphoribosyl-transferase before incorporation into DNA. Antineoplastic activity involves inhibition of purine synthesis, DNA strand breaks, and interference with DNA synthesis. Neither 6-mercaptopurine or 6-thioguanine are very effective against PBT as single agents or in combination regimens [71-73]. Levin and Prados have used

methotrexate

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