Signal transduction inhibition: results from phase I clinical trials in chronic myeloid leukemia.
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.
Druker
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Department of Medicine, Division of Hematology and Medical Oncology, Oregon Health and Science University, Portland, OR 97201, USA.
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*
D000970:Antineoplastic Agents; D001549:Benzamides; D004791:Enzyme Inhibitors; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate