Results of plasma N-terminal pro B-type natriuretic peptide and cardiac troponin monitoring in GIST patients do not support the existence of imatinib-induced cardiotoxicity.

BACKGROUND: Recently, case reports of patients treated with imatinib (imatinib mesylate; Gleevec; Glivec) indicated that this tyrosine kinase inhibitor may induce cardiomyopathy. Consequently, careful cardiac monitoring was advocated for clinical studies. The purpose of this study was to prospectively evaluate whether imatinib (Gleevec) induces early, subclinical, cardiac toxicity. PATIENTS AND METHODS: History and physical examination were carried out with special attention for symptoms of heart failure. Additionally, assessments of serial plasma N-terminal pro B-type natriuretic peptide (NT-proBNP) and serum cardiac troponin T (cTnT) measurement before and 1 and 3 months after the start of imatinib treatment (400-800 mg daily) were done in patients with advanced and/or metastatic gastrointestinal stromal tumours (GIST). RESULTS: A total of 55 GIST patients were enrolled. Only one patient, with a normal pretreatment NT-proBNP, showed an increase in NT-proBNP to above age-specific normal values during imatinib treatment and developed symptomatic heart failure due to pre-existent cardiac valvular disease. cTnT levels remained stable. CONCLUSIONS: In our study population, imatinib treatment for GIST was not associated with an increase in plasma NT-proBNP levels, indicating that the risk of subclinical cardiac toxicity is limited with the use of this agent. These results do not support the current strategy to standard cardiac monitoring in all patients. This may be restricted to GIST patients with a history of cardiac disease.

111Indium-trastuzumab visualises myocardial human epidermal growth factor receptor 2 expression shortly after anthracycline treatment but not during heart failure: a clue to uncover the mechanisms of trastuzumab-related cardiotoxicity.

AIM: Trastuzumab can induce cardiotoxicity, particularly when combined with anthracyclines. Myocardial human epidermal growth factor receptor 2 (HER2) expression may be transiently upregulated by a compensatory mechanism following cardiac stress. 111In-DTPA-trastuzumab, scintigraphy can detect HER2 positive tumour lesions, however previously, we found myocardial uptake in only 1 of the 15 anthracycline-pre-treated patients with a median of 11 months after the last anthracycline administration. To evaluate whether myocardial HER2 expression is upregulated by anthracycline-induced cardiac stress or in case of heart failure by chronic pressure or volume overload, we performed 111In-DTPA-trastuzumab scans in patients shortly after anthracyclines and with non-anthracycline-related heart failure. METHODS: Patients within 3 weeks after undergoing 4-6 cycles first-line anthracycline-based chemotherapy and patients with heart failure due to cardiac disease underwent gammacamera imaging 48 and 96 h after 111In-DTPA-trastuzumab intravenously. RESULTS: Myocardial 111In-DTPA-trastuzumab uptake was observed in 5 out of 10 anthracycline-treated patients, who all were without symptomatic cardiac dysfunction. None of the 10 heart failure patients showed myocardial uptake. CONCLUSION: Shortly after completion of anthracycline treatment, myocardial HER2 over-expression was detectable in 50% of the patients. 111In-DTPA-trastuzumab scintigraphy after anthracyclines prior to adjuvant trastuzumab potentially identifies patients susceptible for trastuzumab-related cardiotoxicity and thus may facilitate the optimal timing of trastuzumab therapy.

Molecular imaging: what can be used today.

Biochemical cellular targets and more general metabolic processes in cancer cells can be visualised. Extensive data are available on molecular imaging in preclinical models. However, innovative tracers move slowly to the clinic. This review provides information on the currently available methods of metabolic imaging, especially using PET in humans. The uptake mechanisms of tracer methods and a brief discussion of the more 'molecular' targeted methods are presented. The main focus is on the different classes of tracers and their application in various types of cancer within each class of tracers, based on the current literature and our own experience. Studies with [18F]FDG (energy metabolism), radiolabelled amino acids (protein metabolism), [18F]FLT (DNA metabolism), [11C]choline (cell membrane metabolism) as general metabolic tracer methods and [18F]DOPA (biogenic amine metabolism) as a more specific tracer method are discussed. As an example, molecular imaging methods that target the HER2 receptor and somatostatin receptor are described.

Use of natriuretic peptides for detecting cardiac dysfunction in long-term disease-free breast cancer survivors.

BACKGROUND: Plasma natriuretic peptides are increased in patients with cardiac dysfunction. N-terminal (NT-ANP) and B-type (BNP) natriuretic peptides were measured in disease-free breast cancer survivors, during long-term follow-up after epirubicin (360 mg/m2 or 450 mg/m2 cumulatively) and chest irradiation. PATIENTS AND METHODS: Plasma samples for natriuretic peptide measurement were repeated after extended follow-up in 54 patients, who had participated in 2 studies evaluating cardiotoxicity. RESULTS: From a median follow-up of 2.7 to 6.5 years, median BNP was raised almost three-fold (p<0.001). Symptomatic heart failure was now present in 2 patients. Compared to the epirubicin 360 mg/m2 group, BNP was higher (p=0.006) in the 450 mg/m2 group, with a trend (p=0.054) for higher NT-ANP. CONCLUSION: These findings suggest that anticancer therapy initiates an autonomically progressive process that may ultimately lead to symptomatic cardiac dysfunction, years after treatment. BNP measurement may be of value to identify patients requiring intensive cardiac follow-up.