[Phase I study of a new floxuridine derivative, 2'-deoxy-3', 5'-di-O-acetyl-5-fluoro-3-(3-methylbenzoyl)uridine (FF-705)].
A phase I study of a new floxuridine derivative, FF-705, was performed in patients with various types of solid tumors. Efficacy of single oral administration with dose range of 300 to 700 mg/body was studied in 12 patients. At a dose of 500 mg/body transient increases of s GOT and s GPT were noted in one patient and, of 700 mg/body, nausea, vomiting or stomach dullness sensation was noted in two patients. The maximum tolerated dose was considered to be 700 mg/body or more. The dose limiting factor was a gastrointestinal toxicity. Oral administration in five consecutive days was studied in 23 patients to doses ranging 100 to 700 mg/body. The incidence of side effects were increased with dose escalation, and at a dose of 700 mg/body side effects were seen in all patients. The maximum tolerated dose was considered to be 700 mg/body/day, and the dose limiting factor was gastrointestinal toxicity. The optimal dose of FF-705 for consecutive administration is considered to be within the range of 200 to 300mg/body/day. Serum and urine concentrations of metabolites were assayed in 7 patients receiving single dose of 600 mg/body. In all patients serum concentration of floxuridine (FUDR) was higher than that of 5-FU and other metabolites at all points of measurement. The highest concentration of FUDR was detected at 2 hours after drug administration and the mean value was 0.04 microgram/ml. The main metabolite in the urine was 5'-acetyl-FUDR which was excreted 0.8% to the dose for 24 hours. The other metabolites were excreted less than 0.2%.
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism; D002214:Capsules; D004334:Drug Administration Schedule; D004341:Drug Evaluation; D005260:Female; D005467:Floxuridine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000378:metabolism
D002214:Capsules; D005467:Floxuridine; C040250:2'-deoxy-3',5'-di-O-acetyl-5-fluoro-3-(3-methylbenzoyl)uridine