Evaluation of biomarkers for cardiotoxicity of anthracyclin-based chemotherapy.
BACKGROUND
The clinical assessment of the myocardial damage caused by anthracyclin (ANT)-therapy is difficult. Therefore a study was performed to evaluate non-invasive markers of anthracyclin-induced cardiac effects, with emphasis on course-to-course variation.


METHODS
Eligible for study participation were patients, without known cardiologic abnormalities who did not use cardiotoxic medication (except for ANT-therapy), who had previously completed at least three cycles of anthracyclin-containing chemotherapy (n = 14) and patients who were ANT-naïve and who were scheduled to receive doxorubicin-containing chemotherapy (n = 12). Seven patients in this last group also completed at least three cycles and were available for follow-up assessments; thus a total population of 21 patients (12F/9M) completed at least three courses ANT-chemotherapy. In these patients blood samples and ECG-recordings were taken within 6 months after completion of ANT-therapy. In 12 patients (10F/2M) assessments were also done before, immediately afterwards and at 24 h after each course of ANT.


CONCLUSIONS
In the patients who completed chemotherapy, NT-proBNP was 277% (n = 21; 95% CI: 86-661%, P < 0.001) higher compared to healthy volunteers. During the first course NT-proBNP rose 269% (n = 12; 167-409%, P < 0.0001) at 24 h post-administration. The linear corrected QT (QTcL) directly after the first administration of ANT increased by 9.56 ms (n = 12; 3.85-15.27, P < 0.001) and this prolongation was still present at 24 h, 11.48 ms (n = 12; 5.61-17.34, P < 0.0001). Both NT-proBNP and QTcL returned to baseline before the start of the next course and a similar pattern was observed during each course. NT-proBNP and QTcL may be useful markers for course-to-course evaluation of anthracyclin-induced cardiotoxicity.
Broeyer
F J F
FJ
Centre for Human Drug Research, Leiden, The Netherlands. fbroeyer@chdr.nl
Osanto
S
S
Ritsema van Eck
H J
HJ
van Steijn
A Q M J
AQ
Ballieux
B E P B
BE
Schoemaker
R C
RC
Cohen
A F
AF
Burggraaf
J
J
D018943:Anthracyclines / Q000009:adverse effects*; D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000139:chemically induced*; D004562:Electrocardiography; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged
D018943:Anthracyclines; D015415:Biomarkers