A PHASE-I STUDY OF ESCALATING INTERFERON ALPHA-2A COMBINED WITH 5-FLUOROURACIL AND LEUCOVORIN IN PATIENTS WITH GASTROINTESTINAL MALIGNANCIES

On the basis of preclinical data showing synergy between 5-fluorouraci l (5-FU), leucovorin (LV) and IFN-alpha-2a, a phase I study was carrie d out to determine the maximum tolerable dose (MTD) of IFN-alpha-2a wi th this combination in patients with gastrointestinal malignancies. Th e treatment consisted of 370 mg/m2 5-FU and 200 mg/m2, LV on days 1 to 5, and IFN-alpha-2a on days 1 to 5 of the first week of chemotherapy and on days 1, 3, 5 of each subsequent week, on a 28-day cycle. Six pa tients with colorectal, 3 with pancreas, 2 with oesophagus, 2 with hep atocellular and one with gastric cancer were treated. At level III (5 X 10(6) U/m2) all patients experienced grade 3 or 4 toxicity during th e first 56 days of treatment and the MTD was declared level II. Grade 3 toxicity comprised of anorexia, mucositis, diarrhoea, and fatigue; i n one instance, grade 4 neutropenia occurred. Ten patients were evalua ble for response, one patient with an oesophageal cancer had a minor r esponse and one patient with rectal cancer and liver metastases had a radiological complete response lasting 3 months. The recommended dose for this schedule in phase II studies is 5-FU 370 mg/m2, LV 200 mg/m2, and IFN-alpha-2a 4 x 10(6) U/m2.