Doxorubicin and paclitaxel versus fluorouracil, doxorubicin, and cyclophosphamide as first-line therapy for women with metastatic breast cancer: Final results of a randomized phase III multicenter trial

Purpose: This phase III trial compared the efficacy and safety of doxorubic in and paclitaxel (AT) to 5-fluorouracil, doxorubicin, and cyclophosphamide (FAC) as first-line therapy for women with metastatic breast cancer. Patients and Methods: A total of 267 women with metastatic breast cancer we re randomized to receive either AT (doxorubicin 50 mg/m(2) followed 24 hour s later by paclitaxel 220 mg/m(2)) or FAC (5-fluorouracil 500 mg/m(2), doxo rubicin 50 mg/m(2), cyclophosphamide 500 mg/m(2)), each administered every 3 weeks for vp to eight cycles. Patients had to have measurable disease and an Eastern Cooperative Oncology Group performance status of 0 to 2. Only o ne prior non-anthracycline, nontaxane-containing adjuvant chemotherapy regi men was allowed. Results: Overall response rates for patients randomized to AT and FAC were 68% and 55%, respectively (P =.032). Median time to progression and overall survival were significantly longer for AT compared with FAC (time to progr ession 8.3 months v 6.2 months [P =.034]; overall survival 23.3 months v 18 .3 months [P =.13]). Therapy was generally well-tolerated (median of eight cycles delivered in each arm). Grade 3 or 4 neutropenia was more common wit h AT than with FAC (89% v 65%; P <.001); however, the incidence of fever an d infection was low. Grade 3 or 4 arthralgia and myalgia, peripheral neurop athy, and diarrhea were more common with AT, whereas nausea and vomiting we re more common with FAC. The incidence of cardiotoxicity was tow in both ar ms. Conclusion: AT conferred a significant advantage in response rare, time to progression, and overall survival compared with FAC. Treatment was well-tol erated with no unexpected toxicities, <(c)> 2001 by American Society of Cli nical Oncology.