Cyclophosphamide, methotrexate and infusional 5-fluorouracil (infusional CMF) in metastatic breast cancer

Bolus 5-fluorouracil (5-FU) is a phase-specific drug with a short plasma ha lf-life that is used in combination with bolus cyclophosphamide and methotr exate in the treatment of breast cancer. The efficacy of 5-FU can be improv ed by continuous intravenous infusion using portable infusion pumps (infusi onal 5-FU). Infusional 5-FU, 200 mg m(-2) day(-1), in combination with stan dard doses of bolus cyclophosphamide and methotrexate, was evaluated in a p hase I/II dose-finding study. The cyclophosphamide and methotrexate were ad ministered in 28-day cycles as follows: cohort 1, cyclophosphamide 600 mg m (-2), days 1 and 8, and methotrexate 40 mg m(-2), day 1; cohort 2, cyclopho sphamide 400 mg m(-2), days 1 and 8, and methotrexate 40 mg m(-2), day 1; c ohort 3, cyclophosphamide 480 mg m(-2), days 1 and 8, and methotrexate 40 m g m(-2), day 1; cohort 4, cyclophosphamide 480 mg m(-2), days 1 and 8, and methotrexate 40 mg m(-2), days 1 and 8. Median overall survival was 10 mont hs (range 3-21 months). Objective tumour responses were seen in 9 of 25 pat ients (36%, 95% CI 18-58%), including 3 of 13 patients (23%) previously tre ated for metastatic disease, Cohorts 1 and 4 proved to be too toxic, with f ive of six patients in cohort 1 and three of four in cohort 4 developing gr ade III/IV neutropenia. The dose intensity of cyclophosphamide achieved was as follows: cohort 1, 82%; cohort 2, 86%; cohort 3, 97%; cohort 4, 900/b. Infusional 5-FU can be administered safely and is effective in combination with cyclophosphamide 480 mg m(-2), days I and 8, and methotrexate 40 mg m- 2, day 1, in the treatment of metastatic breast cancer.