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


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.
Kuwahara
Akiko
A
School of Pharmacy and Pharmaceutical Sciences, Mukogawa Women's University, Nishinomiya, Japan.
Yamamori
Motohiro
M
Nishiguchi
Kohshi
K
Okuno
Tatsuya
T
Chayahara
Naoko
N
Miki
Ikuya
I
Tamura
Takao
T
Inokuma
Tsubasa
T
Takemoto
Yoshiji
Y
Nakamura
Tsutomu
T
Kataoka
Kazusaburo
K
Sakaeda
Toshiyuki
T
D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000532:radiotherapy; D002940:Circadian Rhythm; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy; D005472:Fluorouracil / Q000008:administration & dosage / Q000493:pharmacokinetics; D006801:Humans; D007564:Japan; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D016896:Treatment Outcome
D009944:Organoplatinum Compounds; C053989:nedaplatin; D002945:Cisplatin; D005472:Fluorouracil