RANDOMIZED TRIAL OF CYCLOPHOSPHAMIDE, METHOTREXATE, AND 5-FLUOROURACIL WITH OR WITHOUT ESTROGENIC RECRUITMENT IN WOMEN WITH METASTATIC BREAST-CANCER

Background. The fraction of breast cancer cells undergoing DNA synthes is at any one time is relatively low, which is problematic because mos t chemotherapeutic agents are most effective against dividing cells. E strogens administered in vitro and in vivo can increase breast cancer cell proliferation. A randomized clinical trial was performed to deter mine if estrogenic recruitment could increase the effectiveness of com bination chemotherapy. Methods. One hundred sixty-five women were rand omized, with two excluded from these analyses, to either an intravenou s cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) regimen alo ne (cyclophosphamide, 600 mg/m2; methotrexate, 40 mg/m2; 5-fluorouraci l, 600 mg/m2) or CMF preceded by 3 days of diethylstilbestrol (DES) at a dose of 1 mg orally per day. The planned cycle length was 3 weeks. Results. Objective responses were seen in 20 of 80 patients (25%) trea ted with CMF and 32 of 83 patients (39%) treated with DES-CMF, and thi s difference almost achieved statistical significance (chi-square, two -sided P = 0.06). However, duration of response, time to disease progr ession, and survival time were similar for the two regimens. Conclusio ns. Estrogenic recruitment with DES as used in this study does not sub stantially increase the efficacy of a CMF regimen administered intrave nously every 3 weeks.