Display options
Cite
Swords R, Mahalingam D, Padmanabhan S, et al. Nilotinib: optimal therapy for patients with chronic myeloid leukemia and resistance or intolerance to imatinib. Drug Des Devel Ther. 2009;3:89-101doi: 10.2147/dddt.s3069.
Swords, R., Mahalingam, D., Padmanabhan, S., Carew, J., & Giles, F. (2009). Nilotinib: optimal therapy for patients with chronic myeloid leukemia and resistance or intolerance to imatinib. Drug design, development and therapy, 389-101. https://doi.org/10.2147/dddt.s3069
Swords, Ronan, et al. "Nilotinib: optimal therapy for patients with chronic myeloid leukemia and resistance or intolerance to imatinib." Drug design, development and therapy vol. 3 (2009): 89-101. doi: https://doi.org/10.2147/dddt.s3069
Swords R, Mahalingam D, Padmanabhan S, Carew J, Giles F. Nilotinib: optimal therapy for patients with chronic myeloid leukemia and resistance or intolerance to imatinib. Drug Des Devel Ther. 2009 Sep 21;3:89-101. doi: 10.2147/dddt.s3069. PMID: 19920925; PMCID: PMC2769239.
Copy Download .nbib Format: NLM
Share it on

Drug Des Devel Ther. 2009 Sep 21;3:89-101. doi: 10.2147/dddt.s3069.

Nilotinib: optimal therapy for patients with chronic myeloid leukemia and resistance or intolerance to imatinib.

Drug design, development and therapy

Ronan Swords, Devalingam Mahalingam, Swaminathan Padmanabhan, Jennifer Carew, Francis Giles

Affiliations

  1. Institute for Drug Development, Cancer Therapy and Research Centre, University of Texas Health Science Centre at San Antonio, 7979 Wurzbach Road, San Antonio, TX 78229, USA.

PMID: 19920925 PMCID: PMC2769239 DOI: 10.2147/dddt.s3069

Abstract

Chronic myeloid leukemia (CML) is the consequence of a single balanced translocation that produces the BCR-ABL fusion oncogene which is detectable in over 90% of patients at presentation. The BCR-ABL inhibitor imatinib mesylate (IM) has improved survival in all phases of CML and is the standard of care for newly diagnosed patients in chronic phase. Despite the very significant therapeutic benefits of IM, a small minority of patients with early stage disease do not benefit optimally while IM therapy in patients with advanced disease is of modest benefit in many. Diverse mechanisms may be responsible for IM failures, with point mutations within the Bcr-Abl kinase domain being amongst the most common resistance mechanisms described in patients with advanced CML. The development of novel agents designed to overcome IM resistance, while still primarily targeted on BCR-ABL, led to the creation of the high affinity aminopyrimidine inhibitor, nilotinib. Nilotinib is much more potent as a BCR-ABL inhibitor than IM and inhibits both wild type and IM-resistant BCR-ABL with significant clinical activity across the entire spectrum of BCR-ABL mutants with the exception of T315I. The selection of a second generation tyrosine kinase inhibitor to rescue patients with imatinib failure will be based on several factors including age, co-morbid medical problems and ABL kinase mutational profile. It should be noted that while the use of targeted BCR-ABL kinase inhibitors in CML represents a paradigm shift in CML management these agents are not likely to have activity against the quiescent CML stem cell pool. The purpose of this review is to summarize the pre-clinical and clinical data on nilotinib in patients with CML who have failed prior therapy with IM or dasatinib.

Keywords: chronic myeloid leukemia; imatinib; nilotinib

References

  1. Blood. 2003 Jun 1;101(11):4611-4 - PubMed
  2. N Engl J Med. 2006 Dec 7;355(23):2408-17 - PubMed
  3. J Natl Cancer Inst. 2000 Oct 18;92(20):1641-50 - PubMed
  4. Blood. 2008 Feb 15;111(4):1834-9 - PubMed
  5. Blood. 2006 Oct 1;108(7):2332-8 - PubMed
  6. Pharmacology. 2006;77(1):11-6 - PubMed
  7. Leuk Res. 2006 Nov;30(11):1365-70 - PubMed
  8. Leukemia. 2004 Aug;18(8):1321-31 - PubMed
  9. Cancer Res. 2005 Jun 1;65(11):4500-5 - PubMed
  10. Blood. 2007 Nov 15;110(10):3540-6 - PubMed
  11. Science. 2001 Aug 3;293(5531):876-80 - PubMed
  12. Br J Cancer. 2006 Jun 19;94(12):1765-9 - PubMed
  13. Drugs. 2007;67(2):299-320 - PubMed
  14. Lancet. 2002 Feb 9;359(9305):487-91 - PubMed
  15. Proc Natl Acad Sci U S A. 2006 Jun 13;103(24):9244-9 - PubMed
  16. Leukemia. 2004 Mar;18(3):401-8 - PubMed
  17. Blood. 2003 Jan 15;101(2):690-8 - PubMed
  18. Cancer Cell. 2005 Feb;7(2):129-41 - PubMed
  19. Cancer Cell. 2002 Aug;2(2):117-25 - PubMed
  20. N Engl J Med. 1999 Jul 15;341(3):164-72 - PubMed
  21. Clin Cancer Res. 2005 Jul 1;11(13):4941-7 - PubMed
  22. Leukemia. 2008 Dec;22(12):2176-83 - PubMed
  23. Clin Lymphoma Myeloma. 2007 Mar;7 Suppl 3:S113-9 - PubMed
  24. N Engl J Med. 2003 Mar 13;348(11):994-1004 - PubMed
  25. Mol Cell Biol. 2006 Aug;26(16):6082-93 - PubMed
  26. CA Cancer J Clin. 2006 Mar-Apr;56(2):106-30 - PubMed
  27. Leuk Res. 2006 Dec;30(12):1499-505 - PubMed
  28. Blood. 2005 Nov 1;106(9):3206-13 - PubMed
  29. N Engl J Med. 2006 Jun 15;354(24):2542-51 - PubMed
  30. N Engl J Med. 1999 Apr 29;340(17):1330-40 - PubMed
  31. Blood. 2006 Aug 15;108(4):1328-33 - PubMed
  32. Blood. 2006 Jan 15;107(2):752-9 - PubMed

Publication Types