Weekly high-dose 5-fluorouracil 24-hour infusion and intermediate-dose folinic acid bolus in metastatic colorectal cancer

Background: Weekly high-dose 5-fluorouracil (5-FU; 24-hour infusion of 2.6 g/m(2)) and folinic acid (FA: 500 mg/m(2) as 1- or 2-hour infusion) proved to be effective in patients with metastatic colorectal cancer, The minimum effective dosages of the drugs required in this schedule, however, remain unclear. The aim of this phase II study was to assess, whether a reduction of the dose of 5-FU (2.0 g/m(2)) combined with an intermediate-dose of FA (200 mg/m(2)) is still active in this patient population. Material and Methods: From January 1991 to December 1945 a total of 69 patients with metastatic colorectal cancer, 44 untreated and 25 pretreated patients. were treated with 3 courses of 6 weekly infusions of an intermediate-close 5-FU (2.0 g/m(2)/24 h) and FA (200 mg/m(2) as a bolus). In 12 untreated patients, 5-FU pharmacokinetics were studied by high-performance liquid chromatography (HPLC). Results: 3/44 untreated patients (7%) achieved a complete response, 13/44 (30%) a partial response, 20/44 (45%) a stable disease and in 8/34 patients (18%) the disease was progressive. The probability of median survival in the untreated group was 20 months. Response rates in the pretreated group were inferior with no partial remissions but stable diseases in about 50% of the patients. Sumarizing more than 1000 treatment days, toxicity consisted mainly of mild nausea (n = 24 patients), diarrhea (n = 7) and hand-foot syndrome (n = 10). These side effects were well manageable on an outpatient basis. The mean 5-FU serum steady state level of 0.58 mu g/ml (+/- 0.26) was relatively ion compared to the values noted by other authors: individual levels did not correlate with the experienced grades of toxicity in these patients assessed bg WHO-defined criteria, Conclusion: Weekly: 24-hour infusion of an intermediate-dose 5-FU preceeded by an intermediate-dose FA-bolus is an active regimen with possibly reduced side effects and costs of therapy when compared to the treatment schedule introduced by Ardalan.