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

Abstract

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.

Coordination compounds in cancer: Past, present and perspectives

“…The water solubility of nedaplatin is ten times higher than that of cisplatin. It is actually less nephrotoxic than cisplatin and carboplatin (Alberto et al, 2009;Kuwahara, 2009), presenting anticancer activity comparable to that of cisplatin (Kawai et al, 2005;Alberto et al, 2009). Nedaplatin interacts with DNA forming mainly interstrand cross-links.…”

Nanocarriers for delivery of platinum anticancer drugs

“…Nedaplatin or cis -diammineglycolatoplatinum(II), shows improved toxicological profile compared to cisplatin and pharmacokinetic properties similar to carboplatin [27]. So far it has limited regional approval in treatment of NSCLC, small cell lung cancer (SCLC), oesophageal cancer and head and neck cancers [28].…”

Therapeutic and Radiosensitizing Effects of Armillaridin on Human Esophageal Cancer Cells

“…In vivo xenograft experiments showed moderate tumor inhibitory activity against human esophageal cancer with a relative safety profile in comparison with the standard first-line chemotherapeutic agent cisplatin. Although cisplatin has been used as a recommended chemoradiation regimen, the morbidity additive to radiotherapy toxicity remains the major drawback in clinical application [9, 10]. For combination with radiation therapy, the drugs possessing characteristics of moderate tumor cytotoxicity without major toxicity are regarded as viable candidates.…”