Phase I study of a new antitumor drug, 1-hexylcarbamoyl-5-fluorouracil (HCFU), administered orally: an HCFU clinical study group report.

A phase I study of a new fluorinated pyrimidine, 1-hexylcarbamoyl-5-fluorouracil (HCFU), was performed by a multi-institutional clinical study group using a total of 111 patients with histologically proven malignancies. The characteristic toxic effects were a transient hot sensation and pollakiuria, which occurred 15-120 minutes after oral administration of the drug, continued for 30 minutes to 4 hours, and subsided spontaneously. Gastrointestinal disturbances such as nausea, vomiting, diarrhea, and anorexia, which are common with 5-FU administration, also occurred with HCFU but did so less frequently. The maximum tolerated dose for a single oral administration was estimated to be between 12 and 15 mg/kg and the optimal daily dose for continuous administration was considered to be between 9 and 18 mg/kg, with divided daily administration. Fifty-seven patients received 5-19 mg/kg/day of HCFU for > 4 weeks, including 31 patients with > 60 days' treatment. Cumulative doses were from 9.5 to 166.2 g, with a mean of 26.3 g. Hematopoietic toxicity was slight and hepatic toxicity was questionable. No renal or other cumulative toxicity was observed. In ten of the 57 patients, favorable clinical effects were seen: an active decrease in the size of the solid tumor (three patients), the disappearance of ascites (six), and the improvement of intestinal obstruction due to peritoneal carcinomatosis (one).