PHASE-II TRIAL OF 5-FLUOROURACIL AND THE NATURAL 1-ISOMER OF FOLINIC ACID IN THE TREATMENT OF ADVANCED COLORECTAL-CARCINOMA

Between February 1991 and July 1992, 79 previously untreated patients with metastatic colorectal carcinoma were enrolled in a phase II study of combined 5-fluorouracil (5-FU) and 1-folinic acid (FA). 5-FU 370 m g/m(2)/day was administered for 5 consecutive days as an intravenous ( i.v.) bolus injection preceded by 1-FA 100 mg/m(2)/day with the same a dministration modality. Treatment was given every 4 weeks until progre ssion. 79 patients were evaluable for toxicity and 64 for response. 2 patients (3%) achieved a complete remission and 8 (12.5%) a partial re mission, 33 (52%) had stable disease and 21 patients (33%) had progres sive disease. Median duration of remission was 32.5 weeks and median s urvival for all evaluable patients was 64.5 weeks. Substantial to seve re side-effects occurred in 39% of patients. Dose-limiting toxicity (g rade 3-4) was mainly diarrhoea (18%) and mucositis (15%). Nausea/vomit ing, cutaneous toxicity, leucopenia, alopecia and conjunctivitis of gr ade 3-4 occurred respectively in 6, 4, 2.5, 1 and 1% of cases. Toxicit y appeared to be substantially similar to that characteristic of combi ned 5-FU and the chiral mixture of d,1-FA. Efficacy was within the ran ge of that observed with the 5-FU/d,1-FA combination, although at the lower level.