Indications for Imatinib Mesylate Therapy and Clinical Management

Abstract

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.

A gist of gastrointestinal stromal tumors: A review

“…Estimation of this risk is based on the tumor size, site, mitotic count and tumor rupture (Table 3). A survival benefit is seen in patients with a high risk of recurrence (mitotic count > 5/50 HPF, size > 5 cm, non-gastric location and tumor rupture) [27,29,35,40,[51][52][53][54][55] . In those patients who had received preoperative imatinib and undergone a complete resection, continuation of imatinib at the same dose for 2 years following surgery is recommended.…”

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“…For instance, treatment with imatinib can cause oedema, diarrhoea, vomiting, nausea and sometimes can lead to thrombocytopenia, anaemia and neutropenia [105]. Drugs that inhibit angiogenesis can affect the formation of new blood vessels throughout the body that can lead to dangerous side effects such as bleeding that becomes difficult to manage [106].…”

Kinase drug discovery approaches in chronic myeloproliferative disorders

“…The mechanisms can be defined into four broad categories: (i) decreased intracellular drug levels, due to plasma binding and drug efflux; (ii) increased expression of BCR-ABL kinase; (iii) mutations in the ABL kinase of BCR-ABL affecting drug interaction or kinase activity; and (iv) BCR-ABL mutation-independent mechanisms (Shah et al, 2002). In a pivotal phase III IRIS clinical study, 16% of patients with early chronic-phase CML developed secondary resistance or had disease progression after 42 months after imatinib treatment (Guilhot, 2004;Shah, 2007). In addition, patients with more advanced disease have a higher incidence of resistance.…”