A PHASE-II TRIAL OF CARDIOPROTECTION WITH CARDIOXANE (ICRF-187) IN PATIENTS WITH ADVANCED BREAST-CANCER RECEIVING 5-FLUOROURACIL, DOXORUBICIN AND CYCLOPHOSPHAMIDE

From January 1991 to August 1993, 237 women with metastatic breast can cer were recruited into a multicentric phase II clinical trial designe d to assess the cardioprotective activity of Cardioxane (ICRF-187). Al l patients were treated with 5-fluorouracil 500 mg/m(2), doxorubicin 5 0 mg/m(2), cyclophosphamide 500 mg/m(2) (FDC) and Cardioxane 1000 mg/m (2), in cycles repeated every 3-4 weeks. Cardiac functions were assess ed at baseline by physical examination, ECG, and resting ultrasound le ft ventricle ejection fraction (LVEF). The same tests were repeated re gularly after the 3rd, 6th, 8th cycle and every additional 100 mg/m(2) of doxorubicin. At the end of the study there were 212 evaluable pati ents. Prior to analysis, patients were stratified according to the pre sence of cardiac risks at study entry. One hundred thirty-three patien ts (63%) bore one or more cardiac risks. The average total cumulative dose of doxorubicin administered to the group was 311 mg/m(2) (range: 200-900 mg/m(2)). Overall response (CR + PR) was 49.5% (105/212), with 12% of patients entering complete remission. General toxicity (WHO gr ading) was mild and tolerable; no excessive myelosuppression or relate d symptoms were observed. Three patients from the risk group experienc ed cardiotoxity, with an LVEF fall below 45%, and had to be removed fr om the study. Another 3 patients (1 from the risk group) were removed from the study due to clinically documented congestive heart failure a fter 200, 300 and 400 mg/m(2) of doxorubicin. In our study, Cardioxane (ICRF-187) did not influence the antitumor efficacy of FDC chemothera py, nor did concomitant administration of Cardioxane and chemotherapy result in any other or severer toxicity than that already known for th is regimen. Finally, the observation that 51% of patients with preexis ting cardiac risks received doxorubicin at dose range of 450-900 mg/m( 2) without significant clinical or laboratory signs of cardiotoxicity supports the evidence that Cardioxane provided cardiac protection offe ring the possibility of longer doxorubicin chemotherapy.