Imatinib: the first 3 years

Imatinib (Glivec, formerly STI571, Novartis Pharma AG, Basel, Switzerland) potently inhibits several protein tyrosine kinases, including Bcr-Abl, Kit, and the platelet-derived growth factor receptor. Phase I and II studies demonstrated that orally administered imatinib is highly effective and well tolerated in all phases of chronic myeloid leukemia (CML) at doses ranging from 400 to 600 mg. Importantly, preliminary evidence suggests that patients with advanced CML achieving hematologic or major cytogenetic responses to imatinib may have longer survival than those without such responses, whereas chronic phase patients who respond to treatment may have longer times to disease progression. Ongoing and planned studies are focused on optimizing CML treatment with imatinib, evaluating imatinib-based combination therapy, defining additional therapeutic targets and exploring the use of imatinib in children. In particular, results from several combination phase I studies are expected shortly, including an evaluation of combination imatinib-interferon-alpha therapy and imatinib-cytarabine in chronic phase CML, and a phase I study of single-agent imatinib in children with Philadelphia chromosome-positive leukemia is ongoing. A large phase III trial comparing imatinib with standard inferferon alfa plus cytarabine in first-line CML treatment is also ongoing.