PURPOSE: Capecitabine is a three-step prodrug that was rationally designed to be a more effective and safer alternative to its intermediate metabolite, 5'-deoxy-5-fluorouridine (5'-DFUR). We compared the pharmacokinetics/pharmacodynamics of these drugs in metastatic breast cancer patients. METHODS: Six patients received oral capecitabine at 1657 mg/m2 twice daily and 17 received 5'-DFUR at 400 mg three times daily. Both drugs were administered for 21 days followed by a 7-day rest. RESULTS: Median daily 5'-DFUR AUC was significantly higher for capecitabine than for 5'-DFUR (81.1 vs 32.6 mmol h/l; P = 0.01). Following treatment with 5'-DFUR, the median AUC and Cmax of 5'-DFUR tended to be higher in patients with a partial response (3.83 microg h/ml and 4.88 microg/ml) and stable disease (6.46 microg h/ml and 4.96 microg/ml) than in those with disease progression (2.53 microg h/ml and 1.36 microg/ml). The AUC and Cmax of 5'-DFUR was significantly related to overall survival. CONCLUSIONS: These results support the superiority of capecitabine over 5'-DFUR.
PURPOSE:Capecitabine is a three-step prodrug that was rationally designed to be a more effective and safer alternative to its intermediate metabolite, 5'-deoxy-5-fluorouridine (5'-DFUR). We compared the pharmacokinetics/pharmacodynamics of these drugs in metastatic breast cancerpatients. METHODS: Six patients received oral capecitabine at 1657 mg/m2 twice daily and 17 received 5'-DFUR at 400 mg three times daily. Both drugs were administered for 21 days followed by a 7-day rest. RESULTS: Median daily 5'-DFUR AUC was significantly higher for capecitabine than for 5'-DFUR (81.1 vs 32.6 mmol h/l; P = 0.01). Following treatment with 5'-DFUR, the median AUC and Cmax of 5'-DFUR tended to be higher in patients with a partial response (3.83 microg h/ml and 4.88 microg/ml) and stable disease (6.46 microg h/ml and 4.96 microg/ml) than in those with disease progression (2.53 microg h/ml and 1.36 microg/ml). The AUC and Cmax of 5'-DFUR was significantly related to overall survival. CONCLUSIONS: These results support the superiority of capecitabine over 5'-DFUR.
Authors: Manpreet Bedi; Prajnan Das; John M Skibber; Miguel A Rodriguez-Bigas; George J Chang; Cathy Eng; Robert A Wolff; Nora A Janjan; Sunil Krishnan; Christopher H Crane Journal: Gastrointest Cancer Res Date: 2007-03
Authors: Smitha S Krishnamurthi; Joanna M Brell; Charles L Hoppel; Merrill J Egorin; Karen C Weaver; Xiaolin Li; Stephen T Ingalls; Eleanor G Zuhowski; Mark D Schluchter; Afshin Dowlati; Matthew M Cooney; Joseph Gibbons; Beth A Overmoyer; S Percy Ivy; Scot C Remick Journal: Cancer Chemother Pharmacol Date: 2008-04-15 Impact factor: 3.333
Authors: S G Louie; B Ely; H-J Lenz; K S Albain; C Gotay; D Coleman; D Raghavan; A F Shields; P J Gold; C D Blanke Journal: Br J Cancer Date: 2013-09-10 Impact factor: 7.640