title: Delayed administration of dexrazoxane provides cardioprotection for patients with advanced breast cancer treated with doxorubicin-containing therapy.
abstract: OBJECTIVE
  To assess whether dexrazoxane (DZR) given after a cumulative doxorubicin dose of 300 mg/m2 confers cardioprotection in patients with advanced breast cancer treated with fluorouracil, doxorubicin, and cyclophosphamide (FAC).
  
  
  METHODS
  In two multicenter studies (088001 and 088006), patients were randomized to receive FAC and placebo (PLA) versus FAC and DZR. After a protocol amendment, all patients received open-label DZR after they had reached a cumulative doxorubicin dose of 300 mg/m2. Two groups were compared: 99 patients randomized to the PLA arms before the amendment who received FAC and PLA for at least seven courses (PLA group), and 102 patients randomized to the PLA arms after the amendment who received FAC and PLA for six courses followed by open-label DZR (PLA/DZR group).
  
  
  RESULTS
  The hazards ratio of PLA to PLA/DZR was 3.5 (95% confidence interval [CI], 2.2 to 5.7; P < .001, logrank and generalized Wilcoxon tests) for the doxorubicin dose at any cardiac event, ejection fraction changes, or congestive heart failure (CHF). The hazards ratio of PLA to PLA/DZR was 13.1 (95% CI, 3.7 to 46.0; P < .001, logrank and generalized Wilcoxon tests) for the doxorubicin dose at the development of CHF. The overall incidence of CHF in the PLA/DZR group was 3%, compared with 22% in the PLA group (P < .001, Fisher's exact test). Twenty-six percent of PLA/DZR patients received at least 15 courses of therapy, compared with 5% of patients in the PLA group. These results do not appear to be attributable to a time trend.
  
  
  CONCLUSIONS
  DZR is a highly effective cardioprotective agent when used in patients with advanced breast cancer who continue to receive doxorubicin-based chemotherapy after a cumulative doxorubicin dose of 300 mg/m2 has been reached.
authors.affiliation: Comprehensive Breast Center, Washington, DC 20015-2034, USA. swainsm@aol.com
authors.forename: S M
authors.initials: SM
authors.lastname: Swain
authors.forename: F S
authors.initials: FS
authors.lastname: Whaley
authors.forename: M C
authors.initials: MC
authors.lastname: Gerber
authors.forename: M S
authors.initials: MS
authors.lastname: Ewer
authors.forename: J R
authors.initials: JR
authors.lastname: Bianchine
authors.forename: R A
authors.initials: RA
authors.lastname: Gams
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000903:Antibiotics, Antineoplastic / Q000009:adverse effects*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy*; D002317:Cardiovascular Agents / Q000008:administration & dosage*; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D004311:Double-Blind Method; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects*; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006333:Heart Failure / Q000139:chemically induced / Q000517:prevention & control*; D006801:Humans; D008875:Middle Aged; D011446:Prospective Studies; D011929:Razoxane / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D000903:Antibiotics, Antineoplastic; D002317:Cardiovascular Agents; D011929:Razoxane; D004317:Doxorubicin; D003520:Cyclophosphamide; D005472:Fluorouracil