Combination chemotherapy versus single-agent therapy as first- and second-line treatment in metastatic breast cancer: A prospective randomized trial

Purpose: We report results of a randomized prospective study that compared single agents of low toxicity given both as the first-line and second-line chemotherapy with combination chemotherapy in advanced breast cancer with d istant metastases. Patients and Methods: Patients in the single-agent arm (n = 153) received w eekly epirubicin (8) 20 mg/m(2) until progression or until the cumulative d ose of 1,000 mg/m(2), followed by mitomycin (M) 8 mg/m(2) every 4 weeks, an d those in the combination chemotherapy arm (n = 150) were first given cycl ophosphamide 500 mg/m(2), E 60 mg/m(2), and fluorouracil 500 mg/m(2) three times per week (CEF) followed by M 8 mg/m2 plus vinblastine (V) 6 mg/m(2) e very 4 weeks. Exclusion criteria included age greater than 70 years, World Health Organization (WHO) performance status greater than 2, prior chemothe rapy for metastatic disease, and presence of liver metastases in patients y ounger than 50. Results: An objective response (complete [CR] or partial [PR]) was obtained in 55%, 48%, 16%, and 7% of patients treated with CEF, E, M, and MV, respe ctively. A response to CEF tended to last longer than a response to E (medi an, 12 v 10.5 months; P = .07). Treatment-related toxicity was less in the single-agent arm and quality-of-life (QOL) analysis favored the single-agen t arm, No significant difference in time to progression or survival was fou nd between the two arms. Similarly, no difference in survival was found whe n the patients who received both the planned first-and second-line treatmen ts were compared or when survival was calculated from the beginning of the second line therapy. Conclusion: Patients treated with single-agent E followed by single-agent M had similar survival, but less treatment-related toxicity and better QOL a s compared with those treated with CEF followed by MV. (C) 1998 by American Society of Clinical Oncology.