Drug-induced cardiotoxicity studied by longitudinal B-type natriuretic peptide assays and radionuclide ventriculography.
BACKGROUND
To study the longitudinal variations of plasma B-type natriuretic peptide (BNP) with reference to left ventricular ejection fraction (LVEF) during and after chemotherapy with cardiotoxic drugs.


METHODS
We prospectively measured plasma BNP using an immunoradiometric assay in 12 anthracycline-treated breast cancer patients monitored for a mean time of 880+/-293 days (pilot group). Prior to each cycle and throughout the following year, LVEF and cardiac output were measured by radionuclide ventriculography. Anthracycline pharmacokinetics was studied during the first cycle. Relationships between serial observations were analysed with the general linear mixed effects model. Identical methods were subsequently applied to a test group of 67 anthracycline or trastuzumab-treated patients.


RESULTS
Five out of 70 (6.33%) patients developed anthracycline-induced heart failure. BNP concentrations were found to be positively correlated to anthracycline cumulative dose and negatively to LVEF values. Variables entering the mixed models were cumulative anthracycline dose, time and cardiac output.


CONCLUSIONS
An infra-clinical cardiotoxicity of anthracyclines as defined by BNP elevation is frequent but reversible. Patients who developed heart failure showed a continuous BNP increase and concentrations over 100 ng/ml.
Pichon
M F
MF
Laboratoire d'Oncobiologie, Centre René Huguenin de Lutte Contre le Cancer, 35 rue Dailly 92210 Saint-Cloud France. mf.pichon@stcloud-huguenin.org
Cvitkovic
F
F
Hacene
K
K
Delaunay
J
J
Lokiec
F
F
Collignon
M A
MA
Pecking
A P
AP
D018943:Anthracyclines / Q000009:adverse effects*; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000493:pharmacokinetics; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects; D015415:Biomarkers / Q000097:blood; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy / Q000601:surgery; D002302:Cardiac Output / Q000187:drug effects; D003131:Combined Modality Therapy; D004317:Doxorubicin / Q000009:adverse effects / Q000493:pharmacokinetics; D015251:Epirubicin / Q000009:adverse effects / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood*; D010865:Pilot Projects; D015635:Radionuclide Ventriculography; D018487:Ventricular Dysfunction, Left / Q000097:blood / Q000139:chemically induced*
D018943:Anthracyclines; D000970:Antineoplastic Agents; D015415:Biomarkers; D020097:Natriuretic Peptide, Brain; D015251:Epirubicin; D004317:Doxorubicin