Replacement of cisplatin with nedaplatin in a definitive 5-fluorouracil/cisplatin-based chemoradiotherapy in Japanese patients with esophageal squamous cell carcinoma

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. 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/m(2)/day for days 1-5 and 8-12, infusion of CDDP or NDP at 40 mg/m(2)/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 and 45, and at 5 AM on days 4, 11, 39 and 46. 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.