High-dose infusional 5-fluorouracil combination therapy of metastatic gastric and colorectal cancer.

To improve the therapeutic ratio of palliative chemotherapy in patients with metastatic colorectal and gastric cancer 5-fluorouracil (5-FU) was administered as weekly high-dose 24-hour continuous infusion in combination with leucovorin (LV) and interferon-alpha-2b (IFN) as biomodulating agents: Chemotherapy consisted of a weekly schedule of 500 mg/m2 leucovorin as a 2-hour infusion, followed by a 24-hour continuous infusion of 2500 mg/m2 5-FU. IFN was administered subcutaneously at a dose of 3 mio I.E. three times a week. In patients with gastric carcinoma, etoposide (VP) 100 mg/m2 as 30-minute bolus infusion was added. Eighty-five patients (colorectal: 55 points, gastric: 30 points) are evaluable for response, toxicity, and survival analysis. Colorectal: CP+PR: 19/55 (34.5%), NC: 25/55 (45.5%), PD: 11/55 (20.0%). Median duration of remission in months (90% confidence interval): 5.2 (3.1 to 9.2), median survival since the start of salvage chemotherapy: 13.9 months (12.3 to 20.1), from initial diagnosis of metastasis: 30.2 months (26.3 to 44.5). Gastric: CR: 8/30 (26.7%), PR: 14/30 (46.6), NC: 5/30 (16.7), PD: 3/30 (10.0%). Median duration of remission in months (90% confidence interval): 6.75 (1.5 to 16.2), median survival since start of chemotherapy: 15.1 months (90% confidence interval 11.8 to 20.3 months). Hematologic toxicity: hemoglobin: I: 20.0%, II: 10.0%, leukocytes: I: 13.3%, II: 33.3%, III: 16.6%, platelets: I: 10.0% and III: 3.3%. Hematologic toxicity was moderate to negligible, peripheral toxicity consisted mainly of tolerable stomatitis and diarrhea. Dose and schedule intensified weekly 5-FU combination therapy in metastatic colorectal and gastric cancer is highly active in terms of response and median survival time. Chemotherapy pretreated patients with colorectal cancer seem to have a substantial survival benefit with this salvage protocol.