natriuretic-peptide--brain and Gastrointestinal-Stromal-Tumors

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.. 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).. 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.. 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.

Topics: Administration, Oral; Adult; Aged; Benzamides; Biomarkers; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug-Related Side Effects and Adverse Reactions; Enzyme-Linked Immunosorbent Assay; Female; Follow-Up Studies; Gastrointestinal Stromal Tumors; Heart Failure; Humans; Imatinib Mesylate; Male; Middle Aged; Natriuretic Peptide, Brain; Neoplasm Staging; Peptide Fragments; Piperazines; Probability; Prospective Studies; Pyrimidines; Risk Assessment; Sensitivity and Specificity; Severity of Illness Index; Statistics, Nonparametric; Troponin T

Since its introduction 6 years ago, imatinib mesylate, a selective tyrosine kinase inhibitor, has been a phenomenon in treating chronic myelogenous leukemia (CML) with remarkably superior cytogenetic and molecular response rates at all stages of CML followed by longer progression free survival. Despite its extraordinarily high efficacy, adverse effects of imatinib mesylate such as edema, liver toxicity and fluid retention syndromes have been reported. Here we, for the first time, report development of heart failure in patients on imatinib mesylate medication and the possibility of brain natriuretic peptide (BNP) as a potential diagnostic (or predicting) marker for heart failure. Since plasma BNP levels in the two patients were exceptionally high, we then explored the possibility of genetic association of BNP with the development of heart failure to find no positive association.

Topics: Adult; Aged; Alleles; Base Sequence; Benzamides; Biomarkers, Tumor; Diarrhea; DNA Mutational Analysis; Edema; Exanthema; Female; Gastrointestinal Stromal Tumors; Gene Frequency; Genotype; Heart Failure; Humans; Imatinib Mesylate; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Male; Middle Aged; Natriuretic Peptide, Brain; Piperazines; Polymorphism, Single Nucleotide; Protein Kinase Inhibitors; Pyrimidines; Treatment Outcome