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 distant metastases. Patients and Methods: Patients in the single-agent arm (n = 153) received weekly epirubicin (8) 20 mg/m(2) until progression or until the cumulative dose of 1,000 mg/m(2), followed by mitomycin (M) 8 mg/m(2) every 4 weeks, and those in the combination chemotherapy arm (n = 150) were first given cyclophosphamide 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) every 4 weeks. Exclusion criteria included age greater than 70 years, World Health Organization (WHO) performance status greater than 2, prior chemotherapy for metastatic disease, and presence of liver metastases in patients younger 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, respectively. A response to CEF tended to last longer than a response to E (median, 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-agent arm, No significant difference in time to progression or survival was found between the two arms. Similarly, no difference in survival was found when the patients who received both the planned first-and second-line treatments 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 as compared with those treated with CEF followed by MV. (C) 1998 by American Society of Clinical Oncology.