A randomized comparison of doxifluridine and fluorouracil in colorectal carcinoma

Enhanced therapeutic efficacy of 5'deoxy-5-fluorouridine in 5-fluorouracil resistant head and neck tumours in relation to 5-fluorouracil metabolising enzymes

“…This conversion of 5-FU to FUdR and the cleavage of FUdR are mainly catalysed by a thymidine and/or a uridine-deoxyuridine phosphorylase (Woodman et al, 1980;Peters et al, 1986a). Enzyme kinetics of pyrimidine nucleoside phosphorylase with 5'd-FUR as a substrate were comparable to other studies, about mM (Armstrong & Diasio, 1980;Choong & Lee, 1986;Miwa et al, 1981), which is much higher than that for uridine (Leyva et al, 1983;Laurensse et al, 1988) or thymidine (Wataya & Santi, 1981). So, 5'd-FUR has a low affinity for pyrimidine phosphorylases and might be a substrate for various phosphorylases (Woodman et al, 1980;Choong & Lee, 1986).…”

“…Km values for phosphorylation of FUR (Greenberg et al, 1977), so the concentration of FUR was not rate-limiting. estimate of the conversion of 5-FU to the nucleotide will be obtained (Peters et al, 1986a (Ishitsuka et al, 1980;Armstrong et al, 1980Armstrong et al, , 1983aHartmann & Matter, 1982) although no strict correlation has been demonstrated (Hartmann & Matter, 1982;Peters et al, 1986a). (Siegel & Lin, 1986).…”

“…The prodrug 5'd-FUR (5'-deoxy-5-fluorouridine, Doxifluridine) cannot be converted directly to the nucleotide level due to the presence of a 5-deoxy-ribose moiety and needs to be converted to 5-FU (5-fluorouracil) ( Figure 1) for its activation (Armstrong et al, 1980(Armstrong et al, , 1981(Armstrong et al, , 1983aIshitsuka et al, 1980;Hartmann & Matter, 1982). 5'd-FUR is moderately active in patients (20-30% responders) with various types of tumours (Abele et al, 1984;Alberto et al, 1986Alberto et al, , 1987Hurteloup et al, 1986) and mice (Armstrong & Diasio, 1980;Bollag & Hartmann, 1980;Ishitsuka et al, 1980;Hartmann & Matter, 1982). Plasma level of 5-FU are usually 5-20% of those of 5'd-FUR at a molar level and 5-FU mimics 5'd-FUR pharmacokinetics (Sommadossi et 1983; De Bruijn et al, 1985).…”

Cardiac Toxicity Associated with Capecitabine Therapy

“…5?-deoxy-5-fluorouridine, a metabolite of capecitabine and the immediate precursor to 5-FU, was evaluated in clinical trials using 4 000 mg/m 2 as a 1-h daily intravenous infusion, for 5 days. Cardiac toxicity was observed in 4% to 15% of patients treated with this schedule (22,23).…”

Prospective Multicenter Phase-Ill Trial of Doxifluridine (5’dFUR) versus 5-Fluorouracil in Patients with Advanced Colorectal Carcinoma

“…However, our own experiences [14] with long term continuous infusion of 5'dFUR gave no evidence of neurological side effects but mild to moderate hand and foot syndrome in 50% of patients was observed. A phase-III trial with bolus injection of 5'dFUR versus 5-FU for patients with advanced colorectal carcinoma was termina ted early when one of 52 eligible patients (with no history of cardiac disease) 6 hours after the third 5'dFUR injection developed a ventricular fibrillation [15]. In all these trials different routes of administration were used.…”