Authors: Curran M.P.; Croom K.F.; Goa K.L.

Source: American Journal of Cancer, Volume 2, Number 6, 2003 , pp. 439-454(16)

Publisher: Adis International

Abstract:

Imatinib mesylate (Gleevec^®, Glivec^®) is an orally administered competitive inhibitor of the BCR-ABL tyrosine kinase created by the Philadelphia chromosome (Ph+) in chronic myeloid leukemia (CML).

In patients with newly diagnosed and previously untreated (apart from hydroxyurea and/or anagrelide) CML in the chronic phase, imatinib mesylate 400 mg/day, compared with interferon- (IFN) plus cytarabine, resulted in higher hematologic response (HR) and cytogenetic response (CR) rates and fewer patients progressing to the accelerated phase or blast crisis in a large comparative trial. Preliminary results indicate that, compared with IFN plus cytarabine, imatinib mesylate treatment was associated with similar total costs, but resulted in a higher health-related quality of life (HR-QOL).

Imatinib mesylate was also effective in patients with chronic-phase CML refractory to or intolerant of treatment with IFN (as 400 mg/day) and in those with blast-crisis or accelerated-phase CML (600 mg/day). In the latter groups, HR and CR rates were lower than those in patients with chronic phase CML.

Imatinib mesylate-associated adverse events were common in clinical trials, but were mostly mild to moderate in severity. The most frequently reported adverse events were superficial edema, nausea, muscle cramps, diarrhea, vomiting, and skin rash. Myelosuppression (thrombocytopenia and neutropenia) was also reported, especially in patients with advanced disease. In patients with previously untreated chronic-phase CML, serious adverse events (both hematologic and nonhematologic) were less common with imatinib mesylate than with IFN plus cytarabine treatment.

Conclusion: Imatinib mesylate is a valuable therapy for patients with newly diagnosed Ph+ chronic-phase CML. It is better tolerated and produces higher HR, CR and freedom from progressive disease rates than conventional therapy with IFN plus cytarabine. Preliminary results indicate that, compared with IFN plus cytarabine, imatinib mesylate treatment was associated with similar total costs, but resulted in a higher HR-QOL. Imatinib mesylate is also effective in patients with accelerated-phase and blast-crisis CML, and patients with chronic-phase CML who have failed IFN therapy. Given its efficacy and generally manageable adverse event profile, imatinib mesylate offers an important early treatment option for patients with CML.

Keywords: Adis Drug Evaluations; Chronic myeloid leukaemia, treatment; Imatinib, general; Tyrosine kinase inhibitors, general

Document Type: Research article

Affiliations: 1: Adis International Inc., Yardley, Pennsylvania, USA

Publication date: 2003-01-01

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