[Phase I clinical study of a new fluorinated pyrimidine antineoplastic agent, TAC-278]

A new fluorinated pyrimidine, TAC-278, was studied for its safety, anti-tumor activity and pharmacokinetics in patients with solid tumors of various types. Single oral administration was done in 43 patients with dose range of 50 to 1200 mg. These single administrations caused no side effects but nausea in only one patient daily given 900 mg. Repeated oral dose tolerance was assessed in 79 patients in daily doses of 100 to 1800 mg. Side effects were reported by 26 (33.3%) of the 79 patients. Major side effects were mild gastrointestinal symptoms. The maximum tolerated dose was considered to be 1200 mg/day, over which CNS symptoms as dose limiting factor for TAC-278 developed in some patients. As to the therapeutic effect, minor response was obtained in 2 of the 24 evaluable patients. Concentration of 5-FU in body fluid and tumor tissues were high following oral administration of TAC-278, but the disappearance was relatively rapid. Excretion of TAC-278 occurred predominantly in urine.