Serum cardiac troponin I levels and ECG/Echo monitoring in breast cancer patients undergoing high-dose (7 g/m(2)) cyclophosphamide.
High-dose cyclophosphamide (HD-CTX) is largely employed in high-dose chemotherapy (HD-CHT) protocols. HD-CTX dose-limiting toxicity expresses itself as cardiac toxicity which is fatal in a minority of patients. The pathophysiology of HD-CTX-associated cardiotoxicity is still poorly understood. Autopsy studies in patients who died from acute HD-CTX-induced cardiac toxicity revealed hemorrhagic myocardial cell death and interstitial edema. Recently troponins, in particular troponin I (cTnI), have been found to represent a uniquely sensitive and specific marker of myocyte membrane integrity and therefore to increase in response to minimal myocardial cell damage in different settings, including doxorubicin-induced cardiotoxicity. We performed a multiparametric cardiologic monitoring in 16 consecutive breast cancer patients undergoing HD-CTX by means of serial ECG registrations and cardiac enzymes (CPK, CPK-MB and cTnI) determinations plus echocardiography in order to clarify acute cardiac events following HD-CTX administration. Neither overt cardiac toxicity nor cardiac enzymes elevation were recorded. Serial ECGs revealed in six cases little and reversible reduction of QRS voltage and/or ST abnormalities. Echo monitoring showed in four cases mild and transient increase of LV diastolic/systolic diameter/volume without decrease of FS% or EF% below normal values: in two of them abnormalities of diastolic function (E/A mitral doppler ratio) were also recorded. We conclude that our protocol of HD-CTX administration does not cause myocardial cell damage as analyzed by serum cTnI levels, thus suggesting that myocyte membrane injury may not be the first direct mechanism of HD-CTX cardiotoxicity. ECG (ie QRS voltages ) and Echo (ie E/A ratio) monitoring leads us to hypothesize that slight interstitial edema with reduction of LV diastolic compliance may be initial signs of cardiac dysfunction in this clinical setting.
Morandi
P
P
Division of Medical Oncology, San Bortolo Hospital, Vicenza, Italy.
Ruffini
P A
PA
Benvenuto
G M
GM
La Vecchia
L
L
Mezzena
G
G
Raimondi
R
R
D000328:Adult; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage / Q000633:toxicity*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage; D015415:Biomarkers / Q000097:blood; D001943:Breast Neoplasms / Q000150:complications / Q000188:drug therapy*; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography / Q000187:drug effects*; D005260:Female; D006331:Heart Diseases / Q000097:blood / Q000139:chemically induced / Q000175:diagnosis; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D008875:Middle Aged; D014182:Transplantation, Autologous / Q000009:adverse effects; D019210:Troponin I / Q000097:blood*
D018906:Antineoplastic Agents, Alkylating; D015415:Biomarkers; D019210:Troponin I; D003520:Cyclophosphamide