Journal
CANCER CHEMOTHERAPY AND PHARMACOLOGY
Volume 56, Issue 2, Pages 205-211Publisher
SPRINGER
DOI: 10.1007/s00280-004-0934-7
Keywords
capecitabine; 5 '-DFUR; pharmacokinetics; pharmacodynamics; comparative study; phase II
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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/m(2) 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 C-max of 5'-DFUR tended to be higher in patients with a partial response (3.83 mu g h/ml and 4.88 mu g/ml) and stable disease (6.46 mu g h/ml and 4.96 mu g/ml) than in those with disease progression (2.53 mu g h/ml and 1.36 mu g/ml). The AUC and C-max of 5'-DFUR was significantly related to overall survival. Conclusions: These results support the superiority of capecitabine over 5'-DFUR.
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