, Volume 68, Issue 4, pp 439–447 | Cite as


  • Mark SanfordEmail author
  • Katherine A. Lyseng-Williamson
Adis Drug Profile


  • ▴ 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.


Acute Lymphoblastic Leukemia Clofarabine Prior Chemotherapy Regimen Paediatric Trial Neurological Adverse Event 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Vitale A, Guarini A, Chiaretti S. The changing scene of adult acute lymphoblastic leukemia. Curr Opin Oncol 2006; 18(6): 652–9PubMedCrossRefGoogle Scholar
  2. 2.
    European Medicines Agency. Atriance: scientific discussion [online]. Available from URL: [Accessed 2007 Dec 6]
  3. 3.
    Jabbour EJ, Faderl S, Kantarjian HM. Adult acute lymphoblastic leukemia. Mayo Clin Proc 2005 Nov; 80(11): 1517–27PubMedCrossRefGoogle Scholar
  4. 4.
    Cancer Research UK. UK Non-Hodgkins lymphoma statistics [online]. Available from URL: [Accessed 2007 Dec 13]
  5. 5.
    Song KW, Barnett MJ, Gascoyne RD, et al. Primary therapy for adults with T-cell lymphoblastic lymphoma with hematopoietic stem-cell transplantation results in favorable outcomes. Ann Oncol 2007 Mar; 18(3): 535–40PubMedCrossRefGoogle Scholar
  6. 6.
    Larson RA. Management of acute lymphoblastic leukemia in older patients. Semin Hematol 2006 Apr; 43(2): 126–33PubMedCrossRefGoogle Scholar
  7. 7.
    DeAngelo DJ, Yu D, Johnson JL, et al. Nelarabine induces complete remissions in adults with relapsed or refractory T-lineage acute lymphoblastic leukemia or lymphoblastic lymphoma: Cancer and Leukemia Group B study 19801. Blood 2007 Jun 15; 109(12): 5136–42PubMedCrossRefGoogle Scholar
  8. 8.
    Apostolidou E, Swords R, Alvarado Y. Treatment of acute lymphoblastic leukaemia: a new era. Drugs 2007; 67(15): 2153–71PubMedCrossRefGoogle Scholar
  9. 9.
    Fielding AK, Richards SM, Chopra R, et al. Outcome of 609 adults after relapse of acute lymphoblastic leukemia (ALL): an MRC UKALL 12/ECOG 2993 study. Blood 2007 Feb; 109(3): 944–50PubMedCrossRefGoogle Scholar
  10. 10.
    Appelbaum FR, Rosenblum D, Arceci RJ, et al. End points to establish the efficacy of new agents in the treatment of acute leukemia. Blood 2007 Mar 1; 109(5): 1810–6PubMedCrossRefGoogle Scholar
  11. 11.
    Szafraniec SI, Stachnik KJ, Skierski JS. New nucleoside analogs in the treatment of hematologic disorders. Acta Pol Pharm 2004 May–Jun; 61(3): 223–32PubMedGoogle Scholar
  12. 12.
    Gandhi V, Rodriguez Jr C, Kisor DF, et al. Rationale and design of pharmacologically directed clinical trials of GW506U in refractory hematologic malignancies. Blood 1997 Nov 15; 90 Suppl. 1 (Pt 2): 241Google Scholar
  13. 13.
    Rodriguez Jr CO, Stellrecht CM, Gandhi V. Mechanisms for T-cell selective cytotoxicity of arabinosylguanine. Blood 2003 Sep 1; 102(5): 1842–8PubMedCrossRefGoogle Scholar
  14. 14.
    Kisor DF. Nelarabine: a nucleoside analog with efficacy in T-cell and other leukemias. Ann Pharmacother 2005 Jun; 39(6): 1056–63PubMedCrossRefGoogle Scholar
  15. 15.
    Lambe CU, Averett DR, Paff MT, et al. 2-Amino-6-methoxypurine arabinoside: an agent for T-cell malignancies. Cancer Res 1995; 55(15): 3352–6PubMedGoogle Scholar
  16. 16.
    Gandhi V, Plunkett W, Rodriguez Jr CO. Compound GW506U78 in refractory hematologic malignancies: relationship between cellular pharmacokinetics and clinical response. J Clin Oncol 1998 Nov; 16(11): 3607–15PubMedGoogle Scholar
  17. 17.
    Gandhi V, Plunkett W, Weiler S, et al. Evaluation of the combination of nelarabine and fludarabine in leukemias: clinical response, pharmacokinetics, and pharmacodynamics in leukemia cells. J Clin Oncol 2001 Apr 15; 19(8): 2142–52PubMedGoogle Scholar
  18. 18.
    Ravandi F, Gandhi V. Novel purine nucleoside analogues for T-cell-lineage acute lymphoblastic leukaemia and lymphoma. Expert Opin Investig Drugs 2006 Dec; 15(12): 1601–13PubMedCrossRefGoogle Scholar
  19. 19.
    Cohen M H, Johnson JR, Massie T. Approval summary: nelarabine for the treatment of T-cell lymphoblastic leukemia/lymphoma. Clin Cancer Res 2006 Sep 15; 12(18): 5329–35PubMedCrossRefGoogle Scholar
  20. 20.
    GlaxoSmithKline. Arranon® (nelarabine): US prescribing information [online]. Available from URL: [Accessed 2007 Nov 22]
  21. 21.
    European Medicines Agency. Atriance (nelarabine): summary of product information [online]. Available from URL: [Accessed 2007 Dec 6]
  22. 22.
    Gandhi V, Plunkett W. Clofarabine and nelarabine: two new purine nucleoside analogs. Curr Opin Oncol 2006 Nov; 18(6): 584–90PubMedCrossRefGoogle Scholar
  23. 23.
    Berg SL, Blaney SM, Devidas M, et al. Phase II study of nelarabine (compound 506U78) in children and young adults with refractory T-cell malignancies: a report from the Children's Oncology Group. J Clin Oncol 2005 May 20; 23(15): 3376–82PubMedCrossRefGoogle Scholar
  24. 24.
    Gokbuget N, Arnold R, Atta J, et al. High single drug activity of compound GW506U78 in relapsed T-lymphoblastic leukemia (T-ALL) and T-lymphoblastic lymphoma (T-LBL) offers option for cure with stem cell transplantation [abstract no. 0397]. Haematologica 2005 Jun; 90 Suppl. 2: 157Google Scholar
  25. 25.
    US FDA Centre for Drug Evaluation and Research. Nelarabine review [online]. Available from URL: [Accessed 2007 Nov 9]
  26. 26.
    National Cancer Institute. Common toxicity criteria [online]. Available from URL: [Accessed 2007 Dec 9]
  27. 27.
    US National Institutes of Health. Combination chemotherapy in treating young patients with newly diagnosed T-cell acute lymphoblastic leukemia [online]. Available from URL: [Accessed 2008 Jan 28]

Copyright information

© Adis Data Information BV 2008

Authors and Affiliations

  • Mark Sanford
    • 1
    • 2
    Email author
  • Katherine A. Lyseng-Williamson
    • 1
    • 2
  1. 1.Wolters Kluwer Health ¦ AdisMairangi Bay, North Shore, AucklandNew Zealand
  2. 2.Wolters Kluwer HealthConshohockenUSA

Personalised recommendations