Weekly high-dose infusion of 5-fluorouracil in advanced colorectal cancer

18 patients with advanced colorectal cancer entered a phase I-II study of high-dose 48 h continuous infusion 5-fluorouracil (5-FU) for 6 weeks. 7 patients were included at the first dose level (3 g/m2) and only 1 had serious toxicity (grade 3 diarrhoea and mucositis). 7 patients were included at the second dose level (3.5 g/m2). 6 had a good tolerance to treatment, while the remaining patient had grade 4 leukopenia. 4 patients received 4 g/m2: 3 had severe toxicity (grade 4 diarrhoea, myelosuppression, mucositis, central nervous system), such that the entry of new patients was stopped. Anti-tumour activity was seen in 33% (95% confidence interval 13-59%) of the overall population. Only patients who had not had previous chemotherapy responded to treatment (response rate in this subgroup [43%, 18-71%]). The optimal dose of 5-FU was 3.5 g/m2 weekly for six cycles.