Cardioprotective effect of dexrazoxane in patients with breast cancer treated with anthracyclines in adjuvant setting: a 10-year single institution experience.
OBJECTIVE
Anthracyclines are highly effective and widely used cytotoxic agents, but their application is often limited by cumulative dose-dependent cardiotoxicity. Dexrazoxane has been shown in several clinical trials to prevent the development of this serious toxicity. The aim of our study was to analyze the incidence of cardiac dysfunction over a 10-year period in patients with breast cancer who were treated with anthracycline-based regimens with addition of dexrazoxane, mainly in an adjuvant setting.


METHODS
We conducted a retrospective analysis on a population of women with breast cancer treated at our institution between January 1993 and October 2003. We reviewed patients' medical records and data on patient characteristics, treatment history, and adverse events that were collected, starting from the time of first visit before starting therapy, with the use of software created and designed for clinical records management in our institution (1999 OK-DH). Patients underwent an ECG assessment prior to starting chemotherapy, and were clinically monitored for cardiac failure. Those who developed signs and symptoms suggestive of cardiac dysfunction underwent further ECG. If clinical findings indicated, echocardiography and further cardiologic investigations were performed. The main outcome measure was the development of signs and symptoms indicative of congestive heart failure (CHF).


RESULTS
A total of 318 female patients were treated with an anthracycline (doxorubicin or epirubicin)-based combination chemotherapy regimen during this time, in most cases in the adjuvant setting (n = 285). Most patients (n = 302) had early-stage disease and only 16 women presented with metastatic disease with good life expectancy (at least 1 year). All patients received dexrazoxane 1000 mg/m(2) intravenously prior to anthracycline administration during each chemotherapy cycle. The median follow-up duration was 35 months. During this time, five patients (1.57%) developed signs and symptoms of CHF. No patient at our institution died of heart failure during the period analyzed. Dexrazoxane was well tolerated, with no reports of adverse events associated with this drug.


CONCLUSIONS
The reported incidence of cardiotoxicity in this study represents a marked reduction compared with historical data for patients receiving anthracycline-based chemotherapy without dexrazoxane. Dexrazoxane appears to have a cardioprotective effect in women with early-stage or advanced breast cancer treated with anthracycline-based combination chemotherapy, mainly as an adjuvant treatment. Prospective, randomized, controlled clinical trials in adjuvant setting should be performed to confirm these results.
Testore
Franco
F
Oncology Unit, Ospedale Cardinal Massaia, Asti, Italy.
Milanese
Simona
S
Ceste
Marco
M
de Conciliis
Enrico
E
Parello
Giuseppe
G
Lanfranco
Claudio
C
Manfredi
Roberto
R
Ferrero
Gianfranco
G
Simoni
Carlotta
C
Miglietta
Loredana
L
Ferro
Silvia
S
Giaretto
Lorena
L
Bosso
Giuseppina
G
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy*; D002317:Cardiovascular Agents / Q000009:adverse effects / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage; D004562:Electrocardiography; D015251:Epirubicin / Q000008:administration & dosage; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000139:chemically induced / Q000517:prevention & control*; D006801:Humans; D015994:Incidence; D008017:Life Expectancy; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011929:Razoxane / Q000008:administration & dosage; D012189:Retrospective Studies
D002317:Cardiovascular Agents; D015251:Epirubicin; D011929:Razoxane; D004317:Doxorubicin