Signal transduction inhibition: results from phase I clinical trials in chronic myeloid leukemia

Semin Hematol. 2001 Jul;38(3 Suppl 8):9-14. doi: 10.1016/s0037-1963(01)90112-x.

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.

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / toxicity
  • Benzamides
  • Clinical Trials, Phase I as Topic
  • Enzyme Inhibitors / administration & dosage
  • Humans
  • Imatinib Mesylate
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy*
  • Piperazines / administration & dosage
  • Piperazines / toxicity
  • Pyrimidines / administration & dosage
  • Pyrimidines / toxicity
  • Signal Transduction / drug effects*

Substances

  • Antineoplastic Agents
  • Benzamides
  • Enzyme Inhibitors
  • Piperazines
  • Pyrimidines
  • Imatinib Mesylate