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 cancer were recruited into a multicentric phase II clinical trial designed to assess the cardioprotective activity of Cardioxane (ICRF-187). All patients were treated with 5-fluorouracil 500 mg/m2, doxorubicin 50 mg/m2, cyclophosphamide 500 mg/m2 (FDC) and Cardioxane 1000 mg/m2, in cycles repeated every 3-4 weeks. Cardiac functions were assessed at baseline by physical examination, ECG, and resting ultrasound left ventricle ejection fraction (LVEF). The same tests were repeated regularly after the 3rd, 6th, 8th cycle and every additional 100 mg/m2 of doxorubicin. At the end of the study there were 212 evaluable patients. Prior to analysis, patients were stratified according to the presence of cardiac risks at study entry. One hundred thirty-three patients (63%) bore one or more cardiac risks. The average total cumulative dose of doxorubicin administered to the group was 311 mg/m2 (range: 200-900 mg/m2). Overall response (CR + PR) was 49.5% (105/212), with 12% of patients entering complete remission. General toxicity (WHO grading) was mild and tolerable; no excessive myelosuppression or related symptoms were observed. Three patients from the risk group experienced cardiotoxicity, with an LVEF fall below 45%, and had to be removed from the study. Another 3 patients (1 from the risk group) were removed from the study due to clinically documented congestive heart failure after 200, 300 and 400 mg/m2 of doxorubicin. In our study, Cardioxane (ICRF-187) did not influence the antitumor efficacy of FDC chemotherapy, nor did concomitant administration of Cardioxane and chemotherapy result in any other or severer toxicity than that already known for this regimen. Finally, the observation that 51% of patients with preexisting cardiac risks received doxorubicin at dose range of 450-900 mg/m2 without significant clinical or laboratory signs of cardiotoxicity supports the evidence that Cardioxane provided cardiac protection offering the possibility of longer doxorubicin chemotherapy.