Preliminary report on the efficacy of sequential methotrexate and 5-fluorouracil in advanced breast cancer

Recent in vitro and animal tumor studies suggest that sequential methotrexate (MTX) and 5-fluorouracil (5-FU) may be much more tumoricidal than either drug when used alone or in conventional combinations. Seventeen evaluable female patients with advanced carcinoma of the breast were treated with MTX 200 mg/M2I.V. followed one hour later with 5-FU 600 mg/M2I.V. Leucovorin 10 mg/M2 was begun orally 24 hours later and continued every six hours for six doses. Thirteen of these patients had not responded to prior drug treatment. Of the 17 patients, 11 responded to therapy, 9 had an objective response of greater than 50% tumor regression, and 2 had a minimal response of less than 50% tumor regression. The greatest number of responses was seen in skin and soft tissue. Disease-free interval, hormonal status, and prior therapy, with the exception of MTX and 5-FU containing drug regimens, did not appear to affect response rates. Toxicity was minimal and not life threatening. Based on these results it is believed that large trials with this drug sequence are warranted.