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.


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.
Perik
P J
PJ
Department of Medical Oncology, University of Groningen and University Medical Centre, Groningen, The Netherlands.
Rikhof
B
B
de Jong
F A
FA
Verweij
J
J
Gietema
J A
JA
van der Graaf
W T A
WT
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D001549:Benzamides; D015415:Biomarkers / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D064420:Drug-Related Side Effects and Adverse Reactions / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D046152:Gastrointestinal Stromal Tumors / Q000097:blood / Q000188:drug therapy* / Q000401:mortality; D006333:Heart Failure / Q000097:blood / Q000139:chemically induced*; D006801:Humans; D000068877:Imatinib Mesylate; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood*; D009367:Neoplasm Staging; D010446:Peptide Fragments / Q000097:blood*; D010879:Piperazines / Q000009:adverse effects* / Q000627:therapeutic use; D011336:Probability; D011446:Prospective Studies; D011743:Pyrimidines / Q000009:adverse effects* / Q000627:therapeutic use; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D018709:Statistics, Nonparametric; D020107:Troponin T / Q000097:blood*
D001549:Benzamides; D015415:Biomarkers; D010446:Peptide Fragments; D010879:Piperazines; D011743:Pyrimidines; D020107:Troponin T; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain; D000068877:Imatinib Mesylate