[Phase I study of a new floxuridine derivative, 2'-deoxy-3', 5'-di-O-acetyl-5-fluoro-3-(3-methylbenzoyl)uridine (FF-705)].

Abstract

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%.

• Journal: Gan to kagaku ryoho. Cancer & chemotherapy (Gan To Kagaku Ryoho) Vol. 11 Issue 1 Pg. 143-9 (Jan 1984) ISSN: 0385-0684 [Print] Japan
• PMID: 6230054 (Publication Type: English Abstract, Journal Article)

Chemical References

• Capsules
• Floxuridine
• 2'-deoxy-3',5'-di-O-acetyl-5-fluoro-3-(3-methylbenzoyl)uridine

Topics

• Administration, Oral
• Adult
• Aged
• Breast Neoplasms (drug therapy, metabolism)
• Capsules
• Drug Administration Schedule
• Drug Evaluation
• Female
• Floxuridine (analogs & derivatives, therapeutic use)
• Humans
• Lung Neoplasms (drug therapy, metabolism)
• Male
• Middle Aged
• Neoplasms (drug therapy, metabolism)
• Stomach Neoplasms (drug therapy, metabolism)