A benefit-risk assessment of imatinib in chronic myeloid leukaemia and gastrointestinal stromal tumours.
Targeting constitutively activated tyrosine kinases, such as BCR-ABL, in chronic myeloid leukaemia (CML) and c-KIT in gastrointestinal stromal tumours (GIST) has substantially changed the clinical management of both diseases. The introduction of imatinib, a tyrosine kinase inhibitor mainly targeting BCR-ABL, c-KIT and PDGFR, has profoundly improved the prognosis of both entities, while being surprisingly well tolerated. This article summarizes recent data on clinical efficacy as well as safety aspects of imatinib for treatment of CML and GIST, including a final benefit-risk assessment. Imatinib induces high rates of cytogenetic and molecular responses in all phases of CML and also has substantial activity in GIST patients. In both diseases, only a few adverse effects, such as musculoskeletal and joint pain, muscle cramps, oedema and gastrointestinal symptoms, occur. Most of these are grade I or II toxicities and generally occur during the early phase of treatment (i.e. within the first 2 years). Thus, in view of the low rates of severe toxicities and the extraordinary efficacy of the drug in both diseases, imatinib represents an oral drug with a high benefit-risk ratio for the treatment of CML and GIST.
Wolf
Dominik
D
Internal Medicine V, Department of Hematology and Oncology, and Tyrolean Cancer Research Institute, Medical University Innsbruck, Innsbruck, Austria. dominik.wolf@i-med.ac.at
Rumpold
Holger
H
D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001549:Benzamides; D001942:Breast Feeding; D016503:Drug Delivery Systems; D004347:Drug Interactions; D005260:Female; D046152:Gastrointestinal Stromal Tumors / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000503:physiopathology; D010879:Piperazines / Q000009:adverse effects / Q000627:therapeutic use*; D011247:Pregnancy; D011252:Pregnancy Complications, Neoplastic / Q000188:drug therapy; D011743:Pyrimidines / Q000009:adverse effects / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate