Sequential administration of cyclophosphamide, methotrexate, 5-fluorouracil, and folinic acid as salvage treatment in metastatic breast cancer.

Experimental data show that sequencing methotrexate (MTX) and 5-fluorouracil (5-FU) may result in synergistic antitumor activity. Moreover, the effect of 5-FU is increased by folinic acid (FA), and finally, cyclophosphamide (CPA) produces an expansion of tumor growth fraction, suggesting an increased cytotoxic effect of cycle-specific drugs subsequently administered. Based on these premises, we have performed a Phase II study with CPA (600 mg/m2 i.v., day 1), MTX (200 mg/m2 1-h i.v. infusion, day 7), 5-FU (600 mg/m2 i.v., day 8), and FA (500 mg/m2 2-h i.v. infusion, day 8 plus 15 mg p.o. every 6 h on days 8 and 9) administered every 3 weeks. Thirty-six patients with metastatic breast cancer were admitted into the study. Median age was 52 years, and all but two patients were postmenopausal. Dominant sites of metastases were soft tissues in 10 patients, bones in 7 patients, and viscera in 19 patients. All patients were pretreated with chemo- and/or hormone therapy. Sixteen patients achieved an objective response (44.5%: 1 complete response and 15 partial responses), 8 had stable disease (SD) (22.2%), and 12 progressed (33.3%). Twenty-one patients had previously received conventional CMF in an adjuvant setting (15 patients) or for metastases (6 patients): 1 complete response (CR) and 7 partial responses (PR) were obtained in the first group and 1 in the second. Major toxic effects were hair loss (56.4%), nausea and vomiting (72%), mucositis (52.5%), and leukopenia (61%). A randomized study could be useful to assess the role of sequential CMF versus conventional CMF in metastatic breast cancer patients.

RCT Entities:   Population Interventions Outcomes