DELAYED ADMINISTRATION OF DEXRAZOXANE PROVIDES CARDIOPROTECTION FOR PATIENTS WITH ADVANCED BREAST-CANCER TREATED WITH DOXORUBICIN-CONTAINING THERAPY

Purpose: To assess whether dexrazoxane (DZR) given after a cumulative doxorubicin dose of 300 mg/m(2) confers cardioprotection in patients w ith advanced breast cancer treated with fluorouracil, doxorubicin, and cyclophosphamide (FAC).Patients and Methods: In two multicenter studi es (088001 and 088006), patients were randomized to receive FAC and pl acebo (PLA) versus FAC and DZR. After a protocol amendment, all patien ts received open-label DZR after they had reached a cumulative doxorub icin dose of 300 mg/m(2). Two groups were compared: 99 patients random ized to the PLA arms before the amendment who received FAC and PLA for at least seven courses (PLA group), and 102 patients randomized to th e PLA arms after the amendment who received FAC and PLA for six course s followed by open-label DZR (PLA/DZR group). Results: The hazards rat io of PLA to PLA/DZR was 3.5 (95% confidence interval [CI], 2.2 to 5.7 ; P < .001, log-rank and generalized Wilcoxon tests) for the doxorubic in 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, log-rank end generalized Wilcoxon tests) for the doxorubicin dose at the development of CHF, The overall incide nce of CHF in the PLA/DZR group was 3%, compared with 22% in the PLA g roup (P < .001, Fisher's erect test), Twenty-six percent of PLA/DZR pa tients received at least 15 courses of therapy, compared with 5% of pa tients in the PLA group, These results do not appear to be attributabl e to a time trend. Conclusion: DZR is a highly effective cardioprotect ive agent when used in patients with advanced breast cancer who contin ue to receive doxorubicin-based chemotherapy after a cumulative doxoru bicin dose of 300 mg/m(2) has been reached. (C) 1997 by American Socie ty of Clinical Oncology.