Combined cytotoxic and endocrine therapy in postmenopausal patients with advanced breast cancer. A randomized study of CMF vs CMF plus tamoxifen

Abstract

In this study 263 patients with advanced measurable breast cancer were randomized to receive cyclophosphamide, methotrexate and 5-fluorouracil (CMF) or CMF + tamoxifen (T). Each cycle of CMF (C, 100 mg/m 2 p.o. days 1–14, M 40 mg/m 2 i.v. days 1 and 8, F, 600 mg/m 2 i.v. days 1 and 8) was repeated every 4 weeks. Tamoxifen, 20 mg twice daily, was given continuously. The treatment results have been assessed by external review for the 220 evaluable patients and were the following for the CMF and CMF + T groups, respectively: PD:24 and 10%; NC: 27 and 15%; PR: 29 and 44%; and CR: 20 and 31%. The difference between response (CR + PR) rates is highly significant ( P = 0.0001). The median duration of remission was 12 months in the CMF-treated group and 18 months in patients treated with CMF + T ( P = 0.09). The median duration of survival was 19 months and 24 months respectively ( P = 0.07). However, in the group of responders patients receiving CMF + T survived significantly longer than those who received CMF alone (32 months vs 21 months, P = 0.005). The addition of T appeared to be of benefit in all subgroups. The largest differences were seen in patients with the dominant site of disease in the viscera, in patients with a Karnofsky index of 100, and in patients of more than 60 yr of age. The amount of CMF given was identical in the two treatment groups and there was a trend toward a decrease in dose with increasing age. No relationship between response and dose given was observed. In conclusion, the simultaneous use of T and CMF improves the therapeutic results in patients with advanced breast cancer.