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 infusio n) proved to be effective in patients with metastatic colorectal cance r, The minimum effective dosages of the drugs required in this schedul e, however, remain unclear. The aim of this phase II study was to asse ss, 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 pati ent population. Material and Methods: From January 1991 to December 19 45 a total of 69 patients with metastatic colorectal cancer, 44 untrea ted and 25 pretreated patients. were treated with 3 courses of 6 weekl y infusions of an intermediate-close 5-FU (2.0 g/m(2)/24 h) and FA (20 0 mg/m(2) as a bolus). In 12 untreated patients, 5-FU pharmacokinetics were studied by high-performance liquid chromatography (HPLC). Result s: 3/44 untreated patients (7%) achieved a complete response, 13/44 (3 0%) a partial response, 20/44 (45%) a stable disease and in 8/34 patie nts (18%) the disease was progressive. The probability of median survi val in the untreated group was 20 months. Response rates in the pretre ated group were inferior with no partial remissions but stable disease s in about 50% of the patients. Sumarizing more than 1000 treatment da ys, toxicity consisted mainly of mild nausea (n = 24 patients), diarrh ea (n = 7) and hand-foot syndrome (n = 10). These side effects were we ll 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 v alues 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 intermedi ate-dose 5-FU preceeded by an intermediate-dose FA-bolus is an active regimen with possibly reduced side effects and costs of therapy when c ompared to the treatment schedule introduced by Ardalan.