Of 47 consecutive patients with advanced breast cancer, we randomly assigned 24 to receive Arm A; ACF alone (Adriamycin, Cyclophosphamide, Ftorafur) and 23 to receive Arm B; 2 cycles of ACF alternating one cycle of MVMF (Mitomycin C, Vincristine, Methotrexate, Ftorafur--a combination of drugs not cross-resistant with ACF). The response rate was 66% in Arm A and 52% in Arm B. The median duration of response was significantly longer in Arm B (11 months in Arm A, 28.8 months in Arm B) due to prolongation of duration to administer adriamycin in Arm B. But the median survival time was 30.7 months in Arm A and 24.5 months in Arm B, and significantly longer in Arm A until 10 months. These results were due to the difference in response rate during induction therapy (58% in Arm A, 26% in Arm B) reflected in the dose intensity of Adriamycin (13 mg/m2/w in Arm A, 6.7 mg/m2/w in Arm B) and the higher CR rate in Arm A, because CR cases had a significantly longer survival than PR and NC cases in both arms. We suppose that achieving CR by an intensive regimen containing adriamycin and adopting a non-cross-resistant regimen can help prolong survival in advanced breast cancer.