cytarabine

Cytarabine, also known as cytosine arabinoside or ara-C, is a pyrimidine analog antimetabolite chemotherapy agent used to treat various hematologic malignancies. It is a nucleoside analog of deoxycytidine with an arabinose sugar instead of the deoxyribose, which disrupts DNA synthesis.

Mechanism of action: After cellular uptake, cytarabine is phosphorylated to ara-C triphosphate (ara-CTP). It inhibits DNA polymerase and is incorporated into DNA, causing chain termination and impaired DNA synthesis, with a preference for cells in the S phase of the cell cycle.

Medical use: Cytarabine is a cornerstone of induction therapy for acute myeloid leukemia (AML), commonly in combination with an anthracycline (the 7+3 regimen). It is also used in acute lymphoblastic leukemia (ALL), certain myelodysplastic syndromes, and some non-Hodgkin lymphomas. CNS prophylaxis or treatment may employ intrathecal cytarabine; high-dose regimens are used in select settings. Liposomal cytarabine (DepoCyt) is approved for meningeal involvement by leukemia or lymphoma and provides a slower release.

Administration and dosing: Cytarabine can be given intravenously or subcutaneously in standard regimens, or intrathecally for central nervous system disease. Dosing varies by indication and schedule; higher-dose regimens carry increased risks of neurotoxicity and cerebellar toxicity, especially in elderly patients or with prolonged exposure. Common adverse effects include myelosuppression, mucositis, fever, GI upset, hepatic enzyme elevations, and conjunctivitis (notably with high-dose or intrathecal administration).

History: Cytarabine was developed in the 1950s–1960s and approved for AML in the late 1960s. It remains among the most active agents against AML and is widely used in combination regimens.