QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Résumé Extracto Full Text PDF For Our Patients Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Articles Ahead of Print [Order Reprint] Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Kisor, D. F Search for Related Content PubMed PubMed Citation Articles by Kisor, D. F

NEW DRUG DEVELOPMENTS

Nelarabine: A Nucleoside Analog with Efficacy in T-Cell and Other Leukemias

Associate Professor of Pharmacokinetics, Raabe College of Pharmacy, Ohio Northern University, Ada, OH 45810-6000, fax 419/772-1917, d-kisor{at}onu.edu

Reprints: Dr. Kisor

OBJECTIVE: To present the pharmacology and pharmacokinetics of nelarabine, 9-ß-D-arabinofuranosylguanine (ara-G) and intraleukemic cellular pharmacokinetics of 9-ß-D-arabinofuranosylguanine triphosphate (ara-GTP) generated from the administration of nelarabine, and clinical and safety information relative to nelarabine use in the treatment of hematologic malignancies.

DATA SOURCES: MEDLINE (1966–December 2004) was searched using the English-language key terms 2-amino-6-methoxypurine arabinoside, 506U78, and nelarabine. Data were also obtained from published abstracts.

STUDY SELECTION AND DATA EXTRACTION: Clinical studies evaluating the pharmacokinetics of nelarabine, ara-G, and cellular ara-GTP and use of nelarabine, alone or in combination with other agents for the treatment of hematologic malignancies, were included in this review.

DATA SYNTHESIS: Nelarabine is the water-soluble, 6-methoxy analog of 9-ß-D-ara-G. Nelarabine is readily converted to ara-G by endogenous adenosine deaminase. The half-life of nelarabine is approximately 15 minutes compared with 2–4 hours for ara-G. The clearance of ara-G is higher in children than in adults (0.312 vs 0.213 L x h^-1 x kg^-1). Intracellular ara-GTP elimination is slow relative to nelarabine and ara-G. In pediatric and adult patients, neurologic toxicity is dose limiting. Severe myelosuppression was not consistently observed. Major responses were seen in patients with T-cell malignancies. Patients who responded had significantly higher intracellular ara-GTP concentrations compared with those who did not respond.

CONCLUSIONS: Nelarabine is an effective ara-G prodrug. Nelarabine has significant activity against malignant T-cells and appears to be an important addition to treatments of various leukemias.

Key Words: ara-G, ara-GTP, leukemia, nelarabine, purine nucleoside analog

Published Online, May 3, 2005. www.theannals.com, DOI 10.1345/aph.1E453