IngentaConnect Nelarabine in the treatment of refractory T-cell malignant diseas...

Authors: Kline, Justin¹; Larson, Richard A²

Source: Expert Opinion on Pharmacotherapy, Volume 7, Number 13, September 2006 , pp. 1791-1799(9)

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-β-d-arabinosyl-6-methoxy-9H-guanine), a synthesised guanosine nucleoside and water-soluble prodrug of ara-G (9-β-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.

Keywords: acute lymphoblastic leukaemia; ara-G; lymphoblastic lymphoma; nelarabine

Document Type: Drug Evaluation

DOI: 10.1517/14656566.7.13.1791

Affiliations: 1: 1Section of Hematology/Oncology, Department of Medicine and Cancer Research Center,University of Chicago, Chicago, IL, USA., Email: jkline@medicine.bsd.uchicago.edu 2: 2Section of Hematology/Oncology, Department of Medicine and Cancer Research Center,University of Chicago, Chicago, IL, USA., Email: rlarson@medicine.bsd.uchicago.edu

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Nelarabine in the treatment of refractory T-cell malignant diseases