title: The expanding options for front-line treatment in patients with newly diagnosed CML.
abstract: The past decade has seen remarkable advances in the treatment of chronic myeloid leukemia (CML). The discovery of the underlying cause of CML, a chromosomal translocation resulting in the expression of an aberrant tyrosine kinase, has enabled the rational development of targeted therapy with tyrosine kinase inhibitors (TKIs). The first available TKI, imatinib, dramatically improved survival rates and demonstrated the potential for long-term treatment. A number of additional strategies have been tested to further maximize outcomes in patients with newly diagnosed CML, including newer TKIs, imatinib dose escalation, and combination therapy. The advanced, more potent TKIs, nilotinib and dasatinib, have proven effective for newly diagnosed patients and for those who experience inadequate response or intolerance to imatinib. Randomized phase 3 studies have shown that nilotinib and dasatinib are more efficacious than imatinib in achieving primary study endpoints. Nilotinib was superior to imatinib in the rate of major molecular response at 12 months; dasatinib was superior to imatinib in the rate of complete cytogenetic response by 12 months. These phase 3 studies are ongoing to further define longer-term efficacy and safety. Research on additional contributing signaling pathways in CML, T315I mutations, and other causes of treatment resistance has identified additional potential treatments that are now in early stages of clinical development, with encouraging preliminary results. With continued advances, it is conceivable that the ultimate goal - a cure for CML - is in our sights.
authors.affiliation: H. Lee Moffitt Cancer Center and Research Institute, 13131 Magnolia Drive, 3 East, Rm 3056H, Tampa, FL 33612, USA. javier.pinilla@moffitt.org
authors.forename: Javier
authors.initials: J
authors.lastname: Pinilla-Ibarz
authors.forename: Ian
authors.initials: I
authors.lastname: Flinn
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy*; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors