Int J Med Sci 2009; 6(6):305-311. doi:10.7150/ijms.6.305 This issue
1. School of Pharmacy and Pharmaceutical Sciences, Mukogawa Women's University, Nishinomiya, Japan;
2. Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan;
3. Kobe University Graduate School of Medicine, Kobe, Japan;
4. Faculty of Pharmaceutical Sciences, Kyoto Pharmaceutical University, Kyoto, Japan
Objective: The effects of replacing cisplatin (CDDP) with cis-diammineglycolatoplatinum (nedaplatin, NDP), a second-generation platinum complex, on the pharmacokinetics of 5-fluorouracil (5-FU) were investigated in Japanese patients with esophageal squamous cell carcinoma, who were treated with a definitive 5-FU/CDDP-based chemoradiotherapy.
Methods: Fifty-six patients were enrolled, 49 treated with CDDP and 7 treated with NDP. A course consisted of continuous infusion of 5-FU at 400 mg/m2/day for days 1-5 and 8-12, infusion of CDDP or NDP at 40 mg/m2/day on days 1 and 8, and radiation at 2 Gy/day on days 1 to 5, 8 to 12, and 15 to 19, with a second course repeated after a 2-week interval. Plasma concentrations of 5-FU were determined by high performance liquid chromatography at 5 PM on days 3, 10, 38 and45, and at 5 AM on days 4, 11, 39 and 46.
Results and conclusions: The circadian rhythm in plasma concentrations of 5-FU observed in the case of CDDP was altered when NDP was used instead. The clinical response can be predicted by monitoring plasma concentrations of 5-FU in the CDDP group, but not in the NDP group.
Keywords: nedaplatin, chemoradiotherapy, esophageal squamous cell carcinoma, 5-fluorouracil, plasma concentration