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

Abstract

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 mg/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. I n 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.

Chemotherapy of advanced breast cancer: a controlled randomized trial of cyclophosphamide versus a four-drug combination

“…The value of chemotherapy in advanced breast cancer is established and responders to chemotherapy have been shown to have a longer survival than non-responders (Baker et al, 1974;Canellos et al, 1974a). Many reports have suggested that multiple drugs, in combination, given intermittently are more effective than the agents used singly (Broder and Tormey, 1974), but this has not been shown unequivocally in a clinical trial.…”

Combination versus sequential single agent chemotherapy in advanced breast cancer: associations with metastatic sites and long-term survival

“…Single agent chemotherapy has been compared to 13 combination chemotherapy regimens in randomised trials of patients with advanced breast cancer (Ahman et al, 1974(Ahman et al, , 1987Baker et al, 1974;Canellos et al, 1976;Chlebowski et al, 1979;Hoogstraten et al, 1976;Lemkin & Dollinger, 1973;Mouridsen et al, 1976;Nemoto et al, 1978;Rubens et al, 1975;Smalley et al, 1976). Despite the fact that combination chemotherapy resulted in significantly higher objective response frequency and complete response frequency in six of these trials with duration of response significantly higher in seven of these trials, no increase in overall survival was associated with combination compared to single agent chemotherapy in any trial.…”

“…One prior study has compared sequential single agent chemotherapy beginning with 5-FU to the same agents given in concurrent combination (Baker et al, 1974). In that trial, objective response frequency was somewhat higher for the sequential single agent regimen (53% versus 43%, not significant) and median survival was comparable (10.2 months for sequential versus 8.6 months for combination, not significant).…”

Bilateral Adrenalectomy for Metastatic Breast Carcinoma

“…Patients with a free interval greater than two years ( > 24 months: 26 patients, 16 (14) were found to respond to adrenalectomy. Of particular interest is the objective response rate of 42% (14 pa¬ tients) in 33 patients who had no prior curative therapy and, therefore, no free interval.…”