Functional monitoring of anthracycline cardiotoxicity: a prospective, blinded, long-term observational study of outcome in 120 patients.
BACKGROUND
With increasing doses the highly tumoricidal anthracycline drugs cause heart damage. Based on empirical drug limitations about 10-15% of patients will develop congestive heart failure (CHF) with a mortality of -50% within 2 years on digitalo-diuretic therapy alone. To avoid CHF there is a consensus recommendation that cardiac function should be monitored in close connection with anthracycline administration. As no prospective studies in a larger series have been performed, these recommendations are based on retrospective data on small numbers of patients.


METHODS
In a prospective, blinded observational study 120 patients with advanced breast cancer were followed before, during, and a median 3 years after treatment with epirubicin. They had 604 serial radionuclide measurements of left ventricular ejection fraction (LVEF) that were stored without calculations except in patients who developed a well-defined CHF.


RESULTS
Anthracycline cardiotoxicity was closely correlated with the cumulative dose, with a great variability in individual susceptibility and a dramatic increase with advancing age. With a delayed onset of 3 months or more, epirubicin induced a threatening, slowly progressive deterioration of cardiac function continuing years after treatment. An actuarial estimation of 59% of the patients experienced a 25% relative reduction in LVEF 3 years after 850-1000 mg/m2 of epirubicin and 20% had deteriorated into a CHF. The patients did not spontaneously regain cardiac function whereas continued therapy with a circadian angiotensin-converting enzyme inhibitor for more than 3 months caused a remarkably potent and long-lasting recovery.


CONCLUSIONS
Due to the displaced cardiotoxic manifestation, functional monitoring in close connection with anthracycline administration appears to be a poorly effective method while later monitoring is essential. Current monitoring recommendations should therefore be revised.
Jensen
B V
BV
Department of Oncology, Herlev Hospital, University of Copenhagen, Denmark. BVittrup@Dadlnet.dk
Skovsgaard
T
T
Nielsen
S L
SL
D000328:Adult; D000368:Aged; D000903:Antibiotics, Antineoplastic / Q000009:adverse effects* / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D002311:Cardiomyopathy, Dilated / Q000139:chemically induced* / Q000175:diagnosis / Q000453:epidemiology; D015331:Cohort Studies; D016001:Confidence Intervals; D003718:Denmark; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D015251:Epirubicin / Q000009:adverse effects* / Q000627:therapeutic use; D005260:Female; D005500:Follow-Up Studies; D006334:Heart Function Tests; D006801:Humans; D008875:Middle Aged; D008991:Monitoring, Physiologic / Q000379:methods; D009367:Neoplasm Staging; D019370:Observation; D011336:Probability; D011446:Prospective Studies; D018570:Risk Assessment; D012720:Severity of Illness Index; D016037:Single-Blind Method; D018709:Statistics, Nonparametric; D016019:Survival Analysis; D013997:Time Factors; D016277:Ventricular Function, Left / Q000187:drug effects
D000903:Antibiotics, Antineoplastic; D015251:Epirubicin