, Volume 68, Issue 4, pp 439-447
Date: 17 Sep 2012

Nelarabine

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Abstract

  • ▴ Nelarabine is an anticancer prodrug of arabinofura-nosylguanine (ara-G), which is metabolized in cells to the cytotoxic metabolite ara-G triphosphate (ara-GTP).

  • ▴ Ara-GTP competes with deoxyguanosine triphosphate for incorporation into DNA. Once incorporated, it inhibits DNA synthesis and leads to high molecular weight DNA fragmentation and cell death.

  • ▴ In paediatric and adult patients with T-cell acute lymphoblastic leukaemia or T-cell lymphoblastic lymphoma, nelarabine induced a complete response, with or without complete haematological recovery, in approximately one-fifth of patients who had not responded to, or had relapsed following treatment with, two or more prior chemotherapy regimens.

  • ▴ The median overall survival time was 13.1 and 20.6 weeks in paediatric and adult patients, with corresponding 1-year survival rates of 14% and 29%.

  • ▴ Treatment-emergent adverse events were common, but non-haematological events were mostly of mild or moderate severity.

  • ▴ Neurological events, which may be severe and irreversible, were the most likely adverse events to limit treatment.