Potentiating role of previously administered agents in the combination chemotherapy of breast cancer.

91 women with metastatic breast cancer, who received prior CTX-5FU or CTX-5FU-PRD, were treated in 3 consecutive clinical trials with either CTX-5FU-PRD-MTX-VCR, MTX-VCR, or MTX-VCR-PRD in order to elucidate whether the effectiveness of 5 drugs was due only to the newly added drugs (MTX-VCR +/- PRD) or whether the previously used drugs (CTX-5FU) were necessary as potentiating agents. There were 17 or 39 responders (43%) in the 5-drug group, 3 of 25 (12%) in the MTX-VCR group and 3 of 27 (11%) in the MTX-VCR-PRD group. The survival in the group treated with 5 drugs was significantly longer. Our results show that CTX-5FU-PRD-MTX-VCR was significantly more effective than MTX-VCR or MTX-VCR-PRD used alone after the patient had already had CTX-5FU +/- PRD. Thus, the previously used drugs (CTX-5FU) seemed to improve the response to the new agents (MTX-VCR +/- PRD) by a potentiating action in the subsequent combination. It is concluded that the exploitation of this enhancing effect represents a significant improvement in the treatment options now available.