title: Randomized prospective clinical trial of high-dose epirubicin and dexrazoxane in patients with advanced breast cancer and soft tissue sarcomas.
abstract: OBJECTIVE
  We conducted a randomized trial to evaluate primarily the cardioprotective effect of dexrazoxane (DEX) in patients with advanced breast cancer and soft tissue sarcomas (STS) treated with high-dose epirubicin (EPI). We wished also to determine the value of radioimmunoscintigraphy (RIS) in the assessment of anthracycline cardiotoxicity.
  
  
  METHODS
  Patients with breast cancer (n = 95) or STS (n = 34) received EPI 160 mg/m2 by intravenous (I.V.) bolus every 3 weeks with or without DEX 1,000 mg/m2 I.V. Cardiac monitoring included multigated radionuclide (MUGA) scans with determination of resting left ventricular ejection fraction (LVEF), and RIS with indium 111 antimyosin monoclonal antibodies.
  
  
  RESULTS
  In either disease, antitumor response rates, time to progression, and survival did not significantly differ between the two arms. There was little difference in noncardiac toxicity for the two treatment groups. All methods of cardiac evaluation clearly documented the cardioprotective effect of DEX. Four patients developed congestive heart failure (CHF), all in the EPI arm. The decrease in LVEF from baseline was significantly greater in the control group. An abnormal antimyosin uptake was observed early in both arms and progressively increased during treatment. However, this increase was significantly higher in the EPI group (P = .004).
  
  
  CONCLUSIONS
  DEX significantly protects against the development of cardiotoxicity when high single doses of EPI are used. Apparently, there was no evidence of an adverse impact of DEX on antitumor activity. Although RIS is a sensitive technique in detecting anthracycline cardiac damage, its specificity is low and it cannot be considered a primary test for guiding anthracycline treatment.
authors.affiliation: Department of Medical Oncology II, Regina Elena Institute for Cancer Research, Rome, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Lopez
authors.forename: P
authors.initials: P
authors.lastname: Vici
authors.forename: K
authors.initials: K
authors.lastname: Di Lauro
authors.forename: F
authors.initials: F
authors.lastname: Conti
authors.forename: G
authors.initials: G
authors.lastname: Paoletti
authors.forename: A
authors.initials: A
authors.lastname: Ferraironi
authors.forename: R
authors.initials: R
authors.lastname: Sciuto
authors.forename: D
authors.initials: D
authors.lastname: Giannarelli
authors.forename: C L
authors.initials: CL
authors.lastname: Maini
mesh_terms: D000328:Adult; D000368:Aged; D000903:Antibiotics, Antineoplastic / Q000009:adverse effects* / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D002317:Cardiovascular Agents / Q000627:therapeutic use*; D016903:Drug Monitoring / Q000379:methods*; D015251:Epirubicin / Q000009:adverse effects* / Q000627:therapeutic use; D005260:Female; D006321:Heart / Q000000981:diagnostic imaging / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011446:Prospective Studies; D011877:Radionuclide Imaging; D011929:Razoxane / Q000627:therapeutic use*; D012509:Sarcoma / Q000188:drug therapy* / Q000473:pathology; D016277:Ventricular Function, Left / Q000187:drug effects
chemical_list: D000903:Antibiotics, Antineoplastic; D002317:Cardiovascular Agents; D015251:Epirubicin; D011929:Razoxane