PHASE I STUDY OF A NEW ANTI-TUMOR DRUG, 1-HEXYLCARBAMOYL-5-FLUOROURACIL (HCFU), ADMINISTERED ORALLY - AN HCFU CLINICAL-STUDY GROUP-REPORT

  • 1 January 1980
    • journal article
    • research article
    • Vol. 64  (8-9) , 861-867
Abstract
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 min after oral administration of the drug, continued for 30 min to 4 h, and subsided spontaneously. Gastrointestinal disturbances such as nausea, vomiting, diarrhea and anorexia, which are common with 5-FU [5-fluorouracil] administration, also occurred with HCFU, but did so less frequently. The maximum tolerated dose for a single oral administration was approximately 12-15 mg/kg; the optimal daily dose for continuous administration was between 9 and 18 mg/kg, with divided daily administration. Patients (57) received 5-19 mg/kg per day of HCFU for > 4 wk, including 31 patients with > 60 days'' treatment. Cumulative doses were from 9.5-166.2 g, with a mean of 26.3 g. Hematopoietic toxicity was slight; hepatic toxicity was questionable. No renal or other cumulative toxicity was observed. In 10 of the 57 patients, the following favorable clinical effects were seen: an active decrease in the size of the solid tumor (3 patients), the disappearance of ascites (6), and the improvement of intestinal obstruction due to peritoneal carcinomatosis (1).