Nelarabine in the treatment of refractory T-cell malignant diseases.

Abstract

T-cell haematological malignancies are uncommon, difficult to treat and, with the exception of T-cell acute lymphoblastic leukaemia, often associated with a poor prognosis. Nelarabine (2-amino-9-beta-D-arabinosyl-6-methoxy-9H-guanine), a synthesised guanosine nucleoside and water-soluble prodrug of ara-G (9-beta-D-arabinofuranosylguanine), has recently been approved by the FDA for the treatment of relapsed/refractory T-cell acute lymphoblastic leukaemia and T-cell lymphoblastic lymphoma in adults and children. Similar to other nucleoside analogues, nelarabine acts by inhibiting DNA synthesis and inducing apoptosis in susceptible cells. Ara-G itself is a water-insoluble molecule, making its clinical use difficult. However, nelarabine is water soluble and rapidly converted to ara-G in vivo. Interestingly, it has been demonstrated that ara-GTP accumulates more readily in T-cells than in B-cells, and this discovery created interest in the development of nelarabine for the treatment of T-cell malignancies. The results of early-phase clinical trials evaluating the use of nelarabine in adults and children with refractory T-cell malignancies have been promising. This article describes the development, pharmacology, toxicity and clinical activity of nelarabine, as well as discusses its potential role in the treatment of T-cell haematological malignancies.

• Authors: Justin Kline, Richard A Larson
• Journal: Expert opinion on pharmacotherapy (Expert Opin Pharmacother) Vol. 7 Issue 13 Pg. 1791-9 (Sep 2006) ISSN: 1744-7666 [Electronic] England
• PMID: 16925505 (Publication Type: Journal Article, Review)

Chemical References

• Arabinonucleosides
• nelarabine

Topics

• Animals
• Arabinonucleosides (adverse effects, chemistry, pharmacokinetics, therapeutic use)
• Clinical Trials as Topic
• Humans
• Leukemia, T-Cell (drug therapy)
• Treatment Outcome