Sequential methotrexate plus 5-FU in advanced breast and colorectal cancers: a phase II study.

Fifty-two patients with advanced breast or colorectal cancer have been treated with methotrexate (MTX) (50 mg/m2) followed 6 hours later by 5-FU (600 mg/m2). The mean serum MTX level immediately prior to 5-FU administration was 1.37 mumols/L (1.37 X 10(-6) M). Of 29 evaluable patients with breast cancer (six of whom had received prior chemotherapy), one achieved a complete response and five achieved a partial response (total response rate, 21%). Among 16 evaluable patients with colorectal cancer (three of whom had received prior chemotherapy), there were no objective responses. Although hematologic toxicity was generally mild, mucositis occurred in 20 patients (severe in three), and at least one early death was attributable to toxicity. These results indicate that at doses of MTX and 5-FU which are in general use in combination chemotherapy for breast cancer, sequential treatment does not have a therapeutic advantage. In colorectal cancer, the same combination is inactive.