Update on practical aspects of the treatment of chronic myeloid leukemia with imatinib mesylate.
Imatinib (imatinib mesylate, Gleevec(R) [formerly known as STI571], Novartis Pharmaceuticals, Basel, Switzerland) is a protein tyrosine kinase inhibitor that is approved by the US Food and Drug Administration for patients with all phases of chronic myeloid leukemia (CML). Imatinib is remarkably effective as treatment for CML in the chronic phase (at a dosage of 400 mg/d) and the accelerated phase (at 600 mg/d). At this time, it remains to be seen whether the chronic phase of CML can be extended sufficiently in some patients so that they are functionally "cured," and also whether the increased rate of major molecular response induced by doses of imatinib higher than 400 mg/d will further improve overall survival of patients with CML in the chronic phase. The value of molecular monitoring of response in patients with CML in the chronic phase is examined. Although imatinib 800 mg/d can induce dramatic responses in patients with myeloid blast crisis, lymphoid blast crisis, and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL), the responses are usually incomplete and of short duration. We discuss the role of imatinib in relation to allogeneic stem cell transplantation (particularly in younger patients), recognizing that the data upon which any decisions can be made are relatively immature. Finally, recent data on new tyrosine kinase inhibitors capable of overcoming primary or acquired resistance to imatinib are reviewed.
Zonder
Jeffrey A
JA
Division of Hematology/Oncology, Karmanos Cancer Institute, Wayne State University School of Medicine, 4100 John R., Detroit, MI 48201, USA. zonderj@karmanos.org
Schiffer
Charles A
CA
D000465:Algorithms; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001549:Benzamides; D001752:Blast Crisis / Q000188:drug therapy; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology; D002986:Clinical Trials as Topic; D003131:Combined Modality Therapy; D000069439:Dasatinib; D003875:Drug Eruptions / Q000209:etiology; D004347:Drug Interactions; D004487:Edema / Q000139:chemically induced; D016044:Fusion Proteins, bcr-abl / Q000037:antagonists & inhibitors*; D005767:Gastrointestinal Diseases / Q000139:chemically induced; D006402:Hematologic Diseases / Q000139:chemically induced; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000601:surgery; D010879:Piperazines / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011743:Pyrimidines / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016879:Salvage Therapy; D013844:Thiazoles / Q000627:therapeutic use
D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D013844:Thiazoles; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl; C498826:nilotinib; D000069439:Dasatinib