title: Signal transduction inhibition: results from phase I clinical trials in chronic myeloid leukemia.
abstract: The tyrosine kinase inhibitor, imatinib mesylate (Gleevec, Novartis Pharmaceuticals Corp, East Hanover, NJ) (formerly STI571) showed significant antileukemic activity with minimal toxicity in preclinical studies. Based on these data, a phase I clinical trial was conducted in patients with chronic myeloid leukemia (CML) who failed other treatment options. Once therapeutic doses were attained, 53 of 54 patients (98%) in the chronic phase achieved hematologic remissions. With prolonged therapy of 2 to 5 months duration, a growing percentage of patients achieved cytogenetic responses. Imatinib mesylate also has activity as a single agent in CML blast crisis and in patients with Ph(+) acute lymphocytic leukemia (ALL). Although responses tend not to be durable, 20% of patients with myeloid blast crisis are in continuous remission for periods up to 1 year. Ongoing clinical studies are directed at optimizing the use of imatinib mesylate.
authors.affiliation: Department of Medicine, Division of Hematology and Medical Oncology, Oregon Health and Science University, Portland, OR 97201, USA.
authors.forename: B
authors.initials: B
authors.lastname: Druker
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000633:toxicity; D001549:Benzamides; D017321:Clinical Trials, Phase I as Topic; D004791:Enzyme Inhibitors / Q000008:administration & dosage; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy*; D010879:Piperazines / Q000008:administration & dosage / Q000633:toxicity; D011743:Pyrimidines / Q000008:administration & dosage / Q000633:toxicity; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D004791:Enzyme Inhibitors; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate