[STI571 (Glivec)--a new drug for the treatment of chronic myeloid leukemia].
Chronic myeloid leukaemia (CML) is characterised by the occurrence of the Philadelphia (Ph) chromosome (9/22 translocation) and the formation of a fusion protein--the BCR-ABL transcript with constitutive activation of the BCR-ABL tyrosine kinase and consequent changes in the intracellular signal transduction, which is responsible for the deregulated myeloid cell proliferation. STI571 (signal transduction inhibition number 571) is a potent and selective inhibitor of the BCR-ABL tyrosine kinase. In the chronic phase of the disease, normal peripheral blood values are achieved within the first month of treatment in the large majority of patients and in many patients also a cytogenic response within the following months. The results in the advanced phase are far less favourable, which is explained by the development of resistance owing to reactivation of the BCR-ABL signal transduction. Side effects are primarily nausea, vomiting, various rashes, oedema, most often in the periorbital region, and musculoskeletal symptoms, including muscle cramps. Perspectives for treatment with STI571 are described, as are combinations with alpha-interferon and other cytostatics with a synergistic profile.
Hasselbalch
Hans Carl
HC
Medicinsk afdeling, Amtssygehuset Roskilde, DK-4000 Roskilde.
D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D001549:Benzamides; D002471:Cell Transformation, Neoplastic / Q000187:drug effects; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy*; D010879:Piperazines / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011743:Pyrimidines / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D015398:Signal Transduction / Q000187:drug effects
D000970:Antineoplastic Agents; D001549:Benzamides; D004791:Enzyme Inhibitors; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D011505:Protein-Tyrosine Kinases