Profile of nelarabine: use in the treatment of T-cell acute lymphoblastic leukemia.
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Reilly KM, Kisor DF
Profile of nelarabine: use in the treatment of T-cell acute lymphoblastic leukemia.
Onco Targets Ther. 2009 Feb 18;2:219-28.
- PubMed ID
- 20616909 [ View in PubMed]
- Abstract
Nelarabine is the prodrug of 9-beta-arabinofuranosylguanine (ara-G) and is therapeutically classified as a purine nucleoside analog. Nelarabine is converted to ara-G by adenosine deaminase and transported into cells by a nucleoside transporter. Ara-G is subsequently phosphorylated to ara-G triphosphate (ara-GTP), thereby initiating the therapeutic effect by inhibiting DNA synthesis. Nelarabine has been extensively studied in regards to its pharmacokinetics, and the data have demonstrated that ara-GTP preferentially accumulates in malignant T-cells. Clinical responses to nelarabine have been demonstrated in various T-cell malignancies and appear to correlate with a relatively high intracellular concentration of ara-GTP compared to nonresponders. Therefore, this unique drug feature of nelarabine accounts for clinical utilization in treating adult and pediatric patients with relapsed or refractory T-cell acute lymphoblastic leukemia or T-cell lymphoblastic lymphoma. Neuropathy is the most predominant adverse effect associated with nelarabine and the incidence correlates with the dose administered. Myelosuppression has been observed, with thrombocytopenia and neutropenia as the most common hematologic complications. This article reviews the pharmacology, mechanism of action, and pharmacokinetic properties of nelarabine, as well as nelarabine's clinical efficacy in T-ALL, T-LBL, and other hematologic malignancies. The toxicity profile, dosage, and administration, and areas of ongoing and future research, are also presented.
DrugBank Data that Cites this Article
- Drugs
- Drug Targets
Drug Target Kind Organism Pharmacological Action Actions Nelarabine DNA Nucleotide Humans YesIncorporation into and destabilizationDetails - Drug Enzymes
Drug Enzyme Kind Organism Pharmacological Action Actions Nelarabine Adenosine deaminase Protein Humans NoSubstrateDetails Nelarabine Deoxycytidine kinase Protein Humans NoSubstrateDetails Nelarabine Deoxyguanosine kinase, mitochondrial Protein Humans NoSubstrateDetails