Nelarabine

Abstract

Nelarabine is an anticancer prodrug of arabinofuranosylguanine (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.