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.