Indications for Imatinib Mesylate Therapy and Clinical Management

Abstract Learning Objectives After completing this course, the reader will be able to: Describe the mechanism of action (i.e., the molecular targets) of the anticancer drug imatinib mesylate. Explain how inhibition of these targets confers clinical benefits in specific human cancers. List the most common clinical side effects of imatinib treatment. Manage the side effects of imatinib treatment so as to allow optimal patient management. Access and take the CME test online and receive 1 hour of AMA PRA category 1 credit at http://CME.TheOncologist.com Imatinib mesylate (Gleevec®, Glivec®, formerly STI571; Novartis Pharma AG; Basel, Switzerland) is a rationally-designed, molecularly-specific oral anticancer agent that selectively inhibits several protein tyrosine kinases central to the pathogenesis of human cancer. It has demonstrated remarkable clinical efficacy in patients with chronic myeloid leukemia and malignant gastrointestinal stromal tumors. Treatment with imatinib is generally well tolerated, and the risk for severe adverse effects is low. Adverse effects most commonly include mild-to-moderate edema, nausea and vomiting, diarrhea, muscle cramps, and cutaneous reactions. Hepatic transaminase level elevations and myelosuppression occur less frequently and resolve with interruption of imatinib therapy. In general, the incidence and severity of adverse effects tend to correlate with imatinib dose and, in chronic myeloid leukemia patients, the phase of disease; but, patient age and other factors are also associated with some types of reactions. With prompt and appropriate intervention, adverse effects in imatinib-treated patients have proven to be manageable across the spectrum of severity, and they seldom require permanent cessation of therapy. Dose reduction is not usually necessary, and reduction to subtherapeutic levels is not recommended.