HIGH-DOSE FOLINIC ACID AND 5-FLUOROURACIL ALONE OR COMBINED WITH HYDROXYUREA IN ADVANCED COLORECTAL-CANCER - A RANDOMIZED TRIAL OF THE ITALIAN ONCOLOGY GROUP FOR CLINICAL RESEARCH

Patients with histologically confirmed advanced colorectal cancer were randomized to receive folinic acid (FA; 500 mg/mq in 2-hour intraveno us infusion) and 5-fluorouracil (5FU; 600 mg/mq given as an intravenou s bolus 1 hour after FA), beginning every week for 6 weeks, followed b y a 2-week rest period, either without hydroxyurea (HU, arm A) or with HU (35 mg/kg per day) given orally in three administrations (every 8 hours) starting 6 hours after 5FU administration (arm B). Six weekly d oses were considered one course. One hundred eighty-two patients were randomized in this trial and 162 (89%) were evaluable for response: 81 patients in arm A and 81 patients in arm B. Objective response was ob served in 18 (one complete response and 17 partial responses) of 81 ev aluable patients (22%; 95% confidence interval, 13-31%) in arm A, and 24 (nine complete responses and 15 partial responses) of 81 patients ( 30%; 95% confidence interval, 20-40%) in arm B. There was no differenc e in terms of median time to progression and median survival. Gastroin testinal toxicity was the most frequently observed toxicity in both ar ms. The double modulation of 5FU, FA plus HU does not appear to be bet ter than the classic 5FU plus FA schedule. This trial confirms that 5F U and FA reached a plateau of 20% to 30%.