Evaluation of lecithinized human recombinant super oxide dismutase as cardioprotectant in anthracycline-treated breast cancer patients

Frederik J F Broeyer, Susanne Osanto, Jun Suzuki, Felix de Jongh, Henk van Slooten, Bea C Tanis, Tobias Bruning, Jeroen J Bax, Henk J Ritsema van Eck, Marieke L de Kam, Adam F Cohen, Yutaka Mituzhima, Jacobus Burggraaf, Frederik J F Broeyer, Susanne Osanto, Jun Suzuki, Felix de Jongh, Henk van Slooten, Bea C Tanis, Tobias Bruning, Jeroen J Bax, Henk J Ritsema van Eck, Marieke L de Kam, Adam F Cohen, Yutaka Mituzhima, Jacobus Burggraaf

Abstract

Aim: Anthracycline-induced cardiotoxicity is (partly) mediated by free radical overload. A randomized study was performed in breast cancer patients to investigate whether free radical scavenger super oxide dismutase (SOD) protects against anthracycline-induced cardiotoxicity as measured by changes in echo, electrocardiography and an array of biomarkers.

Method and results: Eighty female, chemotherapy-naïve breast cancer patients (median age 49, range 24-67 years) scheduled for four or five courses of adjuvant 3 weekly doxorubicin plus cyclophosphamide (AC) chemotherapy, were randomly assigned to receive 80 mg PC-SOD (human recombinant SOD bound to lecithin) or placebo, administered intravenously (i.v.) immediately prior to each AC course. The primary end point was protection against cardiac damage evaluated using echocardiography, QT assessments and a set of biochemical markers for myocardial function, oxidative stress and inflammation. Assessments were performed before and during each course of chemotherapy, and at 1, 4 and 9 months after completion of the chemotherapy regimen. In all patients cardiac effects such as increases in NT-proBNP concentration and prolongation of the QTc interval were noticed. There were no differences between the PC-SOD and placebo-treated patients in systolic or diastolic cardiac function or for any other of the biomarkers used to assess the cardiac effects of anthracyclines.

Conclusion: PC-SOD at a dose of 80 mg i.v. is not cardioprotective in patients with breast carcinoma treated with anthracyclines.

Keywords: anthracyclines; biological markers; breast neoplasms; electrocardiography; heart failure; oxidative stress.

© 2014 The British Pharmacological Society.

Figures

Figure 1
Figure 1
Mean left ventricular ejection fraction (A) and E : A ratio (B) for PC-SOD (open circles) and placebo (closed circles) and 95% CIs (PC-SOD down, placebo up) at baseline and 1, 4 and 9 months post-chemotherapy
Figure 2
Figure 2
Mean NT-proBNP (A) concentrations and QTc (B) linearly corrected for heart rate according to Framingham, during chemotherapy and follow-up for PC-SOD (open circles) and placebo (closed circles) and 95% CIs (PC-SOD up, placebo down) during the course and 1, 4, 9 months post-chemotherapy

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