Imatinib Mesylate (IM), a tyrosine kinase inhibitor, has become the first line of therapy for patients with chronic myeloid leukemia (CML) and the standard treatment of advanced gastrointestinal stromal tumors (GIST). A recent publication (

Kerkela et al. Nature 2006;12:908
) suggest that IM might have myocardial toxicity via c-Abl inhibition. Retrospective studies, however, do not show an increase of cardiac hearth failure (CHF) in patients on IM therapy in clinical trials for CML or GIST (
Atallah et al. Blood 2007;110:1233
and
Verweij et al. Eur J Cancer 2007; 43:974
). In order to prospectively evaluate IM cardiotoxicity we included 101 patients with CML on treatment with IM. As control group, we also included 57 patients with myeloproliferative disorders not treated with IM (essential thrombocytemia= 27, CML=12, policitemia vera=11, other diagnosis=7). After informed consent, all patients had a complete clinical evaluation (interview and physical examination), blood samples for Brain Natriuretic Peptide (BNP) were taken and an echocardiographic study was performed. Groups were similar regarding age (median 48 vs. 54 years), gender distribution and cardiac risk factors, except for hypertension (lower prevalence in IM group: 26% vs. 45.6% in controls, p<0.05). Median time of IM treatment was 805 (range 50–2122) days, mean and median actual IM dose were 463mg and 400 mg, respectively. Cardiac symptoms and signs were equally distributed between groups, except for peripheral edema, more frequent in IM group (25% vs 5%, p<0.05). There was no statistical difference regarding BNP levels (24.4± 7.7pg/mL vs. 26.5± 6.7pg/mL), end diastolic volume of left ventricle (49.4± 10.3mL vs. 48.0 ± 10.8mL) and ejection fraction (EF, 69± 16% vs. 68±13%) for IM and control group, respectively. Four patients presented BNP level above the upper normal limit (UNL = 100pg/mL) in IM group and none in control group. There was a trend for an association between BNP above UNL and a higher IM actual dose (P=0.08). Two patients in IM group and none in control group presented an ejection fraction below normal (<55%). This study shows that a systematic deterioration of cardiac function mediated by IM therapy was not observed. However, since some patients presented with alteration of BNP and/or EF, there is still a possibility for isolate cardiotoxicity associated with IM. BNP, a simple test to perform, might be use to identify patients at risk for subsequent CHF while on IM therapy.

Topics:
cardiotoxicity, imatinib mesylate, brain natriuretic peptide, gastrointestinal stromal tumor, brain natriuretic peptide measurement, congestive heart failure, cancer, echocardiography, hypertension, leukemia, myelocytic, chronic

Author notes

Disclosure: No relevant conflicts of interest to declare.

2007, The American Society of Hematology
2007
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