Original Paper

Journal of Cancer Research and Clinical Oncology

, Volume 134, Issue 9, pp 961-968

First online:

Open Access This content is freely available online to anyone, anywhere at any time.

Evaluation of biomarkers for cardiotoxicity of anthracyclin-based chemotherapy

  • F. J. F. BroeyerAffiliated withCentre for Human Drug Research Email author 
  • , S. OsantoAffiliated withLeiden University Medical Center
  • , H. J. Ritsema van EckAffiliated withAdvanced Medical Systems
  • , A. Q. M. J. van SteijnAffiliated withLeiden University Medical Center
  • , B. E. P. B. BallieuxAffiliated withLeiden University Medical Center
  • , R. C. SchoemakerAffiliated withCentre for Human Drug Research
  • , A. F. CohenAffiliated withCentre for Human Drug Research
  • , J. BurggraafAffiliated withCentre for Human Drug Research



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.


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.

Results and 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.


Anthracyclines Cardiotoxicity Biomarkers Electrocardiography