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 cancer progressive after than fluorouracil(Fu)-containing chemotherapy. Encouraging results have been reported with weekly 24-hour FU infusion. The aim of this study was to rest the activity of weekly FU infusion plus modulation with methotrexate and L-leucovorin in pretreated colorectal cancer patients. Seventeen patients with metastatic colorectal carcinoma were treated with methotrexate (40 mg/m² on day 1), L-leucovorin (100 mg/m² as a 4-hour infusion on day 2), and FU (2,600 mg/m² as a 24-hour infusion on day 2). All patients had measurable disease and a performance status of ECOG 0-2. Two of the 17 evaluable patients achieved partial remission (12%; 95% confidence interval 2-24%), 9 had stable disease, and 6 progressive disease, Median time to progression was 4 months (range, 2-8) and median survival was 7 months (range, 3-12+. Toxicity was generally mild or moderate and consisted of mucositis, diarrhea and neutropenia. Pretreated patients with metastatic colorectal carcinoma benefit only marginally from this treatment schedule.