DOUBLE-MODULATION WITH METHOTREXATE AND L-LEUCOVORIN OF WEEKLY 24-HOUR FLUOROURACIL INFUSION IN FLUOROURACIL-REFRACTORY COLORECTAL-CANCER

No effective second-line therapy has been developed for patients with metastatic colorectal cancel progressive after than fluorouracil(FU)-c ontaining chemotherapy. Encouraging results have been reported with we ekly 24-hour FU infusion. The aim of this study was to test the activi ty of weekly FU infusion plus modulation with methotrexate and L-leuco vorin in pretreated colorectal cancer patients. Seventeen patients wit h metastatic colorectal carcinoma were treated with methotrexate (40 m g/m(2) on day I), L-leucovorin (100 mg/m(2) as a 4-hour infusion on da y 2), and FU (2,600 mg/m(2) as a 24-hour infusion on day 2). All patie nts had measurable disease and a performance status of ECOG O-2. Two o f the 17 evaluable patients achieved partial remission (12%; 95% confi dence interval 2-24%), 9 had stable disease, and 6 progressive disease . Median time to progression was 4 months (range, 2-8) and median surv ival was 7 months (range, 3-12+). Toxicity was generally mild or moder ate and consisted of mucositis, diarrhea and neutropenia. Pretreated p atients with metastatic colorectal carcinoma benefit only marginally f rom this treatment schedule.