Dasatinib for the treatment of Philadelphia chromosome-positive chronic myelogenous leukaemia after imatinib failure.
Dasatinib, a potent, oral kinase inhibitor, is presently approved for Philadelphia-positive chronic myelogenous leukaemia (CML) following imatinib failure. In an in vitro study, dasatinib had 325-fold greater potency than imatinib for inhibiting unmutated BCR-ABL. Phase I and II data show that dasatinib 70 mg b.i.d. is effective after imatinib failure in various phases of CML. Comparative data of dasatinib versus high-dose imatinib in patients with resistance or intolerance to imatinib demonstrated that dasatinib was associated with improved response rates and progression-free survival. Side effects of dasatinib, including pleural effusions, are manageable with modification of dose or schedule. Phase III dose optimisation studies and future indications are also discussed.
III. Medizinische Klinik, Abt. Leukaemieforschung, Medizinische Fakultaet Mannheim, University of Heidelberg, 68167 Mannheim, Germany. hochhaus@uni-hd.de
Andreas
A
Hochhaus
D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001549:Benzamides; D000069439:Dasatinib; D019008:Drug Resistance, Neoplasm; D005838:Genotype; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000235:genetics; D010677:Philadelphia Chromosome; D010879:Piperazines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011743:Pyrimidines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D013844:Thiazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D013844:Thiazoles; D000068877:Imatinib Mesylate; D000069439:Dasatinib