Five-drug therapy in advanced breast cancer. Factors Influencing Toxicity and Response

Abstract

Seventy-four women with advanced breast cancer were treated with a combination of continuous oral prednisone (45 mg/day × 2 wks, 30 mg/day × 2 wks, then 15 mg/day) and cyclophosphamide (100 mg/day), and weekly injections of 5-fluorouracil, 500 mg; methotrexate, 25 mg; and vincristine, 1 mg. Thirtyone of 74 showed an objective response to therapy for a median length of 5 months. The responses were seen in soft tissue and visceral metastases. Definite recalcification of lytic bone lesions was seen in only 1 patient. Prior therapy decreased the number of responses to five-drug therapy. With no prior cytotoxic therapy, 11/16 responded; with prior 5-FU therapy 13/25 responded; with both prior 5-FU and alkylating agent therapy, 7/33 responded. The median length of response was similar regardless of prior therapy. Toxicity was moderately severe; dosage modifications were necessary in the majority of patients, and there were seven drug contributory deaths during therapy. After failure of this combination, only 5/28 responded briefly to a variety of therapeutic measures. Comparable survival from first recurrence was seen whether response or failure occurred on five-drug therapy. Trials of sequential vs. combination therapy will be necessary to define the role of combination therapy in advanced breast cancer.