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


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.


CONCLUSIONS
PC-SOD at a dose of 80 mg i.v. is not cardioprotective in patients with breast carcinoma treated with anthracyclines.
Centre for Human Drug Research, Leiden, The Netherlands.
Frederik J F
FJ
Broeyer
Susanne
S
Osanto
Jun
J
Suzuki
Felix
F
de Jongh
Henk
H
van Slooten
Bea C
BC
Tanis
Tobias
T
Bruning
Jeroen J
JJ
Bax
Henk J
HJ
Ritsema van Eck
Marieke L
ML
de Kam
Adam F
AF
Cohen
Yutaka
Y
Mituzhima
Jacobus
J
Burggraaf
D000328:Adult; D000368:Aged; D018943:Anthracyclines / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D066126:Cardiotoxicity / Q000175:diagnosis / Q000517:prevention & control; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D004334:Drug Administration Schedule; D004452:Echocardiography; D004562:Electrocardiography; D005260:Female; D016166:Free Radical Scavengers / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D006801:Humans; D007275:Injections, Intravenous; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood; D009426:Netherlands; D010446:Peptide Fragments / Q000097:blood; D010713:Phosphatidylcholines / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D013482:Superoxide Dismutase / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D055815:Young Adult
D018943:Anthracyclines; D015415:Biomarkers; D002316:Cardiotonic Agents; D016166:Free Radical Scavengers; D010446:Peptide Fragments; D010713:Phosphatidylcholines; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain; D004317:Doxorubicin; D003520:Cyclophosphamide; D013482:Superoxide Dismutase; C434045:lecithinized superoxide dismutase
anthracyclines; biological markers; breast neoplasms; electrocardiography; heart failure; oxidative stress