Appropriate sequencing of tyrosine kinase inhibitors in chronic myelogenous leukemia: when to change? A perspective in 2009.
OBJECTIVE
Kinase inhibitor therapy options for Philadelphia chromosome positive leukemias have rapidly developed and continue to expand. In 2001, imatinib was approved by the US Food and Drug Administration and revolutionized the treatment of chronic myelogenous leukemia (CML); in 2006 and 2007, approval of dasatinib and nilotinib followed for use in imatinib-resistant or intolerant disease; additional kinase inhibitors continue in development to optimize toxicity and circumvent resistance. Decision-making regarding key questions of initial therapy choice, role of allografting, and changes in therapy remains a fluid discussion; this review aims to give a current perspective.


RESULTS
Imatinib remains a highly effective and well characterized choice for patients with CML in chronic phase; long-term toxicity continues to be assessed, and data surrounding stability of response are quite promising. Dasatinib and nilotinib have proven to be highly effective alternate approaches when imatinib is inadequate or intolerable, yet direct comparison in trials is lacking. Limited clinical and molecular data can aid in decision-making between these agents.


CONCLUSIONS
Multiple options exist today for the treatment of Philadelphia chromosome positive leukemias. Careful monitoring of response and categorization based on guidelines, utilization of molecular diagnostics, particularly kinase domain mutation analysis, as well as early review of allograft options, can allow for efficient and optimal management of the chronic phase CML patient.
Mauro
Michael J
MJ
Center for Hematologic Malignancies, OHSU Knight Cancer Institute, Oregon Health and Science University, Portland, USA. maurom@ohsu.edu
D001549:Benzamides; D000069439:Dasatinib; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy*; D010879:Piperazines / Q000009:adverse effects / Q000627:therapeutic use*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011743:Pyrimidines / Q000009:adverse effects / Q000627:therapeutic use*; D013844:Thiazoles / Q000627:therapeutic use*
D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D013844:Thiazoles; D000068877:Imatinib Mesylate; C498826:nilotinib; D000069439:Dasatinib