PHASE-I TRIAL OF 5-FLUOROURACIL BY 24-HOUR INFUSION WEEKLY

A novel schedule of 5-fluorouracil administration has been developed f or biochemical modulation studies. In combination with the pyrimidine synthesis inhibitor PALA, 5-fluorouracil has been given as a 24-hour i nfusion, repeated weekly: a dose of 2600 Mg/M2 is well tolerated. To i dentify a suitable dose of 5-fluorouracil as a single agent on this sc hedule, we treated 26 patients at doses ranging from 2800 to 3400 mg/m 2 per week. Two-thirds of the patients had failed previous therapy, an d most were symptomatic from their disease. Over half of the patients had metastatic colorectal cancer. The dose-limiting toxicity was diarr hea: Grade 3 or 4 toxicity occurred at every level tested. Twenty-two of the 26 patients required therapy interruption because of toxicity. The severity of this toxicity indicated that escalation of 5-fluoroura cil on this schedule beyond the 2600 mg/M2 known to be tolerated in th e PALA-containing regimen, would be impractical. Two patients, both wi th previously untreated colorectal cancer, had partial remissions last ing three and five months respectively. This dose-intense schedule of 5-fluorouracil administration will be explored further in large-scale randomized trials.