title: Imatinib mesylate, the first molecularly targeted gene suppressor.
abstract: OBJECTIVE
  To review the pharmacology, pharmacokinetics, efficacy, safety, and drug-drug and drug-food interactions of imatinib and the economic considerations of imatinib in the treatment of chronic myeloid leukemia (CML).
  
  
  METHODS
  Literature accessed through MEDLINE (January 1970-January 2002), abstracts from the 2001 annual meetings of the American Society of Clinical Oncology and the American Society of Hematology, imatinib product labeling, and additional studies or abstracts identified from the bibliographies of the reviewed literature were used to compile data. Key search terms were allogeneic bone marrow transplant and stem cell transplant, chronic myeloid leukemia, imatinib, interferon, Gleevec, leukemia, gastrointestinal stromal tumors, STI-571, and tyrosine kinase inhibitors.
  
  
  RESULTS
  Imatinib is a distinctively characteristic drug targeted toward inhibition of tyrosine kinase activity. Imatinib is indicated for the treatment of patients with CML who failed interferon (IFN)-alpha therapy and for the treatment of patients with gastrointestinal stromal tumors (GISTs) expressing the tyrosine kinase receptor c-kit. Imatinib produces positive short-term hematologic and cytogenetic responses in patients with CML; short-term positive objective responses have been shown for patients with GISTs. To our knowledge, there are no controlled trials demonstrating long-term safety, improvement in disease-related symptoms, or increased survival with imatinib. Serious adverse effects requiring dosage decreases and/or therapy termination are edema, hepatotoxicity, and hematologic toxicity. Imatinib also has been found to inhibit tyrosine kinases involved in the growth of other malignancies. The role of imatinib in tumors that express a tyrosine kinase is constantly evolving with new research results.
  
  
  CONCLUSIONS
  Imatinib therapy should be limited to patients whose tumor growth is related to a genetically defective tyrosine kinase. In cases of CML, imatinib should be further limited to patients who have tried and failed IFN-alpha therapy or who are not candidates for an allogeneic stem cell transplant.
authors.affiliation: Pharmacy Care Management, Henry Ford Health System, Detroit, Michigan, USA.
authors.forename: Vanita K
authors.initials: VK
authors.lastname: Pindolia
authors.forename: Barbara J
authors.initials: BJ
authors.lastname: Zarowitz
mesh_terms: D000970:Antineoplastic Agents / Q000191:economics / Q000494:pharmacology / Q000627:therapeutic use*; D001549:Benzamides; D002986:Clinical Trials as Topic; D004347:Drug Interactions; D019008:Drug Resistance, Neoplasm; D018565:Food-Drug Interactions; D005770:Gastrointestinal Neoplasms / Q000188:drug therapy; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy; D010353:Patient Education as Topic; D010879:Piperazines / Q000191:economics / Q000494:pharmacology / Q000627:therapeutic use*; D011743:Pyrimidines / Q000191:economics / Q000494:pharmacology / Q000627:therapeutic use*; D012509:Sarcoma / Q000188:drug therapy; D017154:Stromal Cells
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate