Evaluation of combination vs. sequential cytotoxic chemotherapy in the treatment of advanced breast cancer

Combination chemotherapy has been used in the treatment of acute leukemia, malignant lymphoma, and, more recently, solid tumors. This study was designed to randomize between combination 5-fluorouracil (5-FU) cyclophosphamide, and vincristine sulfate, vs. sequential use of these drugs in patients with breast carcinoma. Forty-six patients received 5-FU 7.5 nig/kg, cyclophosphamide 4 mg/kg daily for 5 days, and vincristine sulfate 0.015 mg/kg on days 1 and 8, repeated monthly. Thirty patients received a single drug in full dose (5-FU 15 mg/kg, cyclophosphamide 8 mg/kg daily for 5 days in monthly course, or vincristine sulfate.02 mg/kg weekly). The design was such that if the patient's tumor failed to respond to the single agent, the subsequent drug was used. In the combination group, 20 (43.5%) had objective responses. The mean survival of the combination group was 8.6 months. Sixteen of the 30 patients (53.3%) receiving sequential therapy responded to one or more of the three drugs. Mean survival of this group was 10.2 months. Evaluation of the drug toxicity between sequential vs. combined therapy revealed three drug-related deaths in the patients treated with 5-fluorouracil alone, with one death in the combination-treated group. Statistical analysis showed no significant difference in tumor response or patient survival between patients treated with these three drugs used in sequence or in combination.