Capecitabine Versus Classical Cyclophosphamide, Methotrexate, and Fluorouracil As First-Line Chemotherapy for Advanced Breast Cancer

Purpose We compared oral capecitabine, administered intermittently or continuously, versus classical cyclophosphamide, methotrexate, and fluorouracil (CMF) as first-line chemotherapy for women with advanced breast cancer unsuited to more intensive regimens. Patients and Methods Three hundred twenty-three eligible women were randomly assigned to capecitabine administered intermittently (1,000 mg/m 2 twice daily for 14 of every 21 days; n 107) or continuously (650 mg/m 2 twice daily for 21 of every 21 days; n 107), or to classical CMF (oral cyclophosphamide 100 mg/m 2 days 1 to 14 with intravenous methotrexate 40 mg/m 2 and fluorouracil 600 mg/m 2 on days 1 and 8 every 28 days; n 109). The primary end point was quality-adjusted progression-free survival (PFS); secondary end points included PFS, overall survival (OS), objective tumor response, and adverse events. Intermittent and continuous capecitabine were to be compared first and, if similar (P .05), combined for definitive comparisons versus CMF. Results Quality-adjusted PFS (P .2), objective tumor response rate (20%; P .8), and PFS (median, 6 months; hazard ratio [HR], 0.86; 95% CI, 0.67 to 1.10; P .2) were similar in women assigned capecitabine versus CMF. OS was longer in women assigned capecitabine rather than CMF (median, 22 v 18 months; HR, 0.72; 95% CI, 0.55 to 0.94; P .02). Febrile neutropenia, infection, stomatitis, and serious adverse events were more common with CMF; hand-foot syndrome was more common with capecitabine. Conclusion Capecitabine improved OS by being similarly active, less toxic, and more tolerable than CMF. Capecitabine is a good first-line chemotherapy option for women with advanced breast cancer who are unsuited to more intensive regimens.