The FDA ( Food and Drug Administration ) has approved Sprycel ( Dasatinib ), an oral inhibitor of multiple tyrosine kinases, for the treatment of adults in all phases of chronic myeloid leukemia ( CML ) ( chronic, accelerated, or myeloid or lymphoid blast phase ) with resistance or intolerance to prior therapy, including Imatinib ( Gleevec ).
The FDA also approved Sprycel for the treatment of adults with Philadelphia chromosome-positive acute lymphoblastic leukemia ( Ph+ALL ) with resistance or intolerance to prior therapy.

Dasatinib is the first approved oral tyrosine kinase inhibitor predicted to bind to multiple conformations of the ABL kinase based on modeling studies.
At nanomolar concentrations, Dasatinib inhibits BCR-ABL, SRC family ( SRC, LCK, YES, FYN ), c-KIT, EPHA2, and PDGFR-beta.
By targeting these kinases, Dasatinib inhibits the overproduction of leukemia cells in the bone marrow of patients with CML and Ph+ALL and allows normal red cell, white cell, and blood platelet production to resume.

Dasatinib provides a new treatment option for patients with CML or Ph+ALL who are resistant or intolerant to Imatinib.

Known mechanisms of Imatinib resistance include mutations in the protein sequence of the BCR-ABL tyrosine kinase, multi-drug resistance gene overexpression, and the activation of alternate signaling pathways involving the SRC family kinases.
For many patients with CML, the risk of developing resistance increases with the number of years of prior treatment and severity of disease. Patients with advanced Ph+ALL generally develop resistance more rapidly than CML patients, including those in blast phase ( an average of 2 months versus 10 months, respectively ).

Source: FDA, 2006


XagenaMedicine2006