Imatinib mesylate for the treatment of chronic myeloid leukemia.
Chronic myeloid leukemia (CML) is the first human malignancy for which the promise of targeted therapy has come true. CML is invariably associated with a specific genetic lesion--the t(9;22) chromosomal translocation. As a consequence of this translocation, a BCR-ABL fusion gene is formed on the 22q- derivative (traditionally known as the Philadelphia chromosome) and the deregulated tyrosine kinase activity of the protein encoded by this gene has been shown to be both necessary and sufficient for initiation and maintenance of the disease. Imatinib mesylate, an orally available tyrosine kinase inhibitor that targets Bcr-Abl, entered clinical evaluation in 1998. Its efficacy surpassed almost everyone's predictions, and the observation of high response rates and favorable toxicity profile associated with imatinib therapy led to its approval as first-line treatment for all newly diagnosed CML patients over an exceptionally short period of time. The 6-year results of the Phase III trial have recently been reported and confirm durability of responses and declining incidence of adverse events over time, although, at present, occurrence of unexpected side effects in the long term cannot be excluded. Although imatinib does not 'cure' CML and has to be administered chronically to patients, it has revolutionized both outcome and quality of life of CML patients.
Soverini
Simona
S
Department of Hematology & Oncological Sciences "Lorenzo e Ariosto Seràgnoli" University of Bologna, Via Massarenti 9, 40138 Bologna, Italy. simona.soverini@tin.it
Martinelli
Giovanni
G
Iacobucci
Ilaria
I
Baccarani
Michele
M
D000970:Antineoplastic Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001549:Benzamides; D002986:Clinical Trials as Topic; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000503:physiopathology; D010879:Piperazines / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D011743:Pyrimidines / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011788:Quality of Life; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000068877:Imatinib Mesylate