title: Cardioprotective effect of dexrazoxane in patients with breast cancer treated with anthracyclines in adjuvant setting: a 10-year single institution experience.
abstract: 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.
authors.affiliation: Oncology Unit, Ospedale Cardinal Massaia, Asti, Italy.
authors.forename: Franco
authors.initials: F
authors.lastname: Testore
authors.forename: Simona
authors.initials: S
authors.lastname: Milanese
authors.forename: Marco
authors.initials: M
authors.lastname: Ceste
authors.forename: Enrico
authors.initials: E
authors.lastname: de Conciliis
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Parello
authors.forename: Claudio
authors.initials: C
authors.lastname: Lanfranco
authors.forename: Roberto
authors.initials: R
authors.lastname: Manfredi
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Ferrero
authors.forename: Carlotta
authors.initials: C
authors.lastname: Simoni
authors.forename: Loredana
authors.initials: L
authors.lastname: Miglietta
authors.forename: Silvia
authors.initials: S
authors.lastname: Ferro
authors.forename: Lorena
authors.initials: L
authors.lastname: Giaretto
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Bosso
mesh_terms: 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
chemical_list: D002317:Cardiovascular Agents; D015251:Epirubicin; D011929:Razoxane; D004317:Doxorubicin