title: Second-generation tyrosine kinase inhibitors: the future of frontline CML therapy.
abstract: All available data from ongoing studies of second-generation tyrosine kinase inhibitors (TKIs) for treatment of patients with newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP) were reviewed. In two nilotinib phase 2 trials, the speed and depth of molecular and cytogenetic responses were greater than responses to imatinib. Furthermore, only one patient in each study progressed to accelerated or blastic phase. In the phase 3 ENESTnd study, molecular and cytogenetic responses to nilotinib were superior to imatinib, and more patients achieved undetectable levels of disease with nilotinib. Nilotinib also demonstrated significantly lower progression than did imatinib. In the ongoing phase 2 study of dasatinib, the speed and depth of molecular and cytogenetic responses were higher compared with expected responses to imatinib; no patient to date has progressed. In the phase 3 DASISION study, molecular and cytogenetic responses to dasatinib were superior to those of imatinib and fewer patients progressed. The results suggest that second-generation TKIs have the potential to replace imatinib as the standard of care for patients with early CML-CP. Future CML therapy might include earlier use of these agents to help more patients achieve complete molecular response and may be a path to a CML cure.
authors.affiliation: The University of Texas, M.D. Anderson Cancer Center, Houston, Texas 77030, USA. hkantarj@mdanderson.org
authors.forename: Hagop M
authors.initials: HM
authors.lastname: Kantarjian
authors.forename: Michele
authors.initials: M
authors.lastname: Baccarani
authors.forename: Elias
authors.initials: E
authors.lastname: Jabbour
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Saglio
authors.forename: Jorge E
authors.initials: JE
authors.lastname: Cortes
mesh_terms: D000814:Aniline Compounds / Q000494:pharmacology / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D000069439:Dasatinib; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy*; D009570:Nitriles / Q000494:pharmacology / Q000627:therapeutic use; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D011743:Pyrimidines / Q000494:pharmacology / Q000627:therapeutic use; D011804:Quinolines / Q000494:pharmacology / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D013844:Thiazoles / Q000494:pharmacology / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000814:Aniline Compounds; D000970:Antineoplastic Agents; D009570:Nitriles; D011743:Pyrimidines; D011804:Quinolines; D013844:Thiazoles; C471992:bosutinib; D011505:Protein-Tyrosine Kinases; C498826:nilotinib; D000069439:Dasatinib